6
Surgery of Cervical and Substernal Goiter
Whitney Liddy, James L. Netterville, Selen Soylu, Gregory W. Randolph
“Guttur homini tantum et suibus intumescit aquarum quae potantur plerumque vitio.” (Translation: Swelling
of the throat occurs only in men and swine, caused mostly by the water they drink.)
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Video 6.1 Surgery for Cervical and Substernal Goiter.
This chapter contains additional online-only content, including an exclusive
video, Surgery for Cervical and Substernal Goiter available on expertconsult.com.
The word goiter is derived from “guttur,” the Latin term for throat.2
Surgery for goiter is as complex as it is rewarding. With goiter, the nor-
mally complex neck base anatomy is distorted in sometimes predictable
and often unpredictable patterns. Size, goiter vascularity, distortion of
anatomy, substernal extension, and restrictions imposed by the bony
confines of the thoracic inlets can make recurrent laryngeal nerve
(RLN) and parathyroid gland identification and preservation challeng-
ing. William Halsted wrote that “the extirpation of the thyroid gland
for goiter better typifies perhaps than other operations, the supreme
triumph of the surgeon’s art.”3
Please see the Expert Consult website for more discussion of this topic.
This chapter reviews the patterns of anatomic distortion presented by
both cervical and substernal goiter. Substernal goiter represents a distinct
subtype of cervical goiter and is discussed separately where appropriate,
given its unique challenges. After reviewing key points regarding goiter’s
definition and clinical evaluation, we shall discuss treatment options,
with an emphasis on the surgical approach. The chapter highlights the
evaluation of upper airway compromise in patients with goiter, the
relationship between the extent of surgery and the likelihood of goiter
recurrence, and the predictive risk factors for surgical complications.
See also Chapter 7, Approach to the Mediastinum: Transcervical, Trans-
sternal, and Video-Assisted; Chapter 8, The Surgical Management of
Hyperthyroidism; and Chapter 9, Reoperation for Benign Thyroid
Disease.
GENERAL CONSIDERATIONS
Goiter Definition
First, it is important to come to an understanding regarding what a
“goiter” is and to define “big.” This is not easy when one looks critically
at the literature. Both greatest diameter and goiter weight have been
used to define thyroid enlargement. In the studies, methods for deter-
mining goiter size range from physical examination measured in cen-
timeters, to physical examination estimated in grams, to surgical
specimen measured in centimeters or grams. Preoperative imaging
diameters may also be used.
The definition of goiter varies substantially among reports.
McHenry suggested 80 g and Russell 100 g, whereas Clark proposed
200 g as the threshold value.5-9 Studies investigating radioiodine
—Pliny the Elder, 1st century AD1
treatment for multinodular goiter often define significant goiter as
greater than 100 g. Hegedus, Nygaard, and Hansen found that goiter
surgical specimens averaged 30 g for unilateral resection and 64 g for
bilateral resection.10 In the study by Katlic, Grillo, and Wang, the aver-
age weight of substernal goiter was 104 g (range 25 to 357 g), with the
greatest diameter averaging 9 cm (range 5 to 19 cm).11 In a series of
more than 200 cervical and substernal goiters treated at Massachusetts
Eye and Ear Infirmary and Massachusetts General Hospital, the mean
weight was 143 g and the mean goiter size was 10.5 cm.12
Please see the Expert Consult website for more discussion of
this topic.
Substernal Goiter Definition
Substernal goiter and its subtypes have been variously termed retroster-
nal, subclavicular, intrathoracic, mediastinal, aberrant, wandering, and
spring goiter, as well as goiter mobile and goiter plongeant. Numerous
definitions and classification schemes have been proposed for
substernal goiter.
Please see the Expert Consult website for more discussion of this topic.
A classification system for substernal goiters is most useful when it takes
into account the features of substernal goiters that must be appreciated to
extract these goiters safely. We define substernal goiter simply as a goiter
that is associated with substernal extension such that the thoracic
component requires mediastinal dissection to facilitate extraction. We
believe that all substernal goiters require axial computed tomography
(CT) scanning to differentiate between the various subtypes. Such differ-
entiation provides tremendously useful surgical information. We pro-
pose the following substernal goiter classification scheme (Table 6.1).
ANTERIOR MEDIASTINAL GOITER (SUBSTERNAL
GOITER TYPE I)
Most surgical and radiographic series suggest that substernal goiters
affect the anterior mediastinum in approximately 85% of patients
and the posterior mediastinum in approximately 15% (see
Table 6.1).26-29 Extension into the anterior mediastinum brings the
mass anterior to the subclavian and innominate vessels and anterior
to the RLN. The relationship of the anterior mediastinal goiter to the
RLN is the same as the normal cervical gland—that is, the nerve is deep.
POSTERIOR MEDIASTINAL GOITER (SUBSTERNAL
GOITER TYPE II)
When substernal goiter expands to the posterior mediastinum, it
excavates the region posterior to the trachea, pushing the trachea
53
 53.e1

The operative story of goiter documents the evolution of modern sur-

gical technique. In 1864, Gunther described a case emphasizing the dif-
ficulties experienced during early goiter surgery: “After several fruitless
attempts at ligation of the arteries, the severe hemorrhage was con-
trolled by compression day and night during eight days by persons
alternating with each other at the task” (see Chapter 1, History of
Thyroid and Parathyroid Surgery).4
53.e2
The largest goiter we can find documented in the literature is reported
by Manoppo, who described a benign, nontoxic goiter that was 75 
60  45 cm. The patient was unable to walk or sit because of the size
of the goiter. Treatment was with right hemithyroidectomy under local
anesthesia without major complications.13
The World Health Organization (WHO) 1960 grading system for
clinical assessment of goiter defines stage 0 as no enlargement; stages
1 to 3 describe progressive goiter enlargement. Stage 1A includes
patients with palpable abnormalities; stage 1B includes patients with
palpable and visual abnormalities with the neck in extension. Stage 2
is defined as a goiter that is visible with the neck in neutral position,
and Stage 3 as a goiter that is able to be visualized at a considerable dis-
tance.14,15 The WHO 1994 goiter classification system is more stream-
lined. Grade 0 is defined as no palpable or visual abnormality. Grade 1
is defined as a palpable thyroid mass that is not visualized with the neck
in neutral position and grade 2 as a visually apparent mass with the
neck in neutral position.16

Lahey and Swinton defined substernal goiter as a “gland in which the
greatest diameter of the intrathoracic component by x-ray was well
below the upper aperture of the thoracic inlet.”17 In 1939, Crile simply
defined substernal goiter as a lesion extending to the aortic arch.18
Lindskog and Goldenberg in 1957 defined substernal goiter as a goiter
whose lower border radiographically reaches the transverse process of
the fourth thoracic vertebra or lower.19 Katlic, Grillo, and Wang
described substernal goiter as greater than 50% of the goiter present
substernally.11 Sanders et al. defined substernal goiter as that which
requires mediastinal exploration and dissection for removal.20 Other
definitions have been offered.21-23
Several workers have offered substernal classification schemes. Hig-
gins based his classification scheme on the percentage of goiter in the
neck versus the percentage of goiter in the chest, with less than 50% in
the chest being described as incomplete intrathoracic, greater than 80%
in the chest as complete intrathoracic, and other categories, including
53.e3
extension below the sternum (substernal [complete or incomplete])
and extension below the clavicle (subclavicular [complete or incom-
plete]).24 Cho, Cohen, and Som offered a grading system relating grade
to percentage of goiter within the chest. Grade I is defined as 0% to 25%
of the goiter within the chest, grade II as 26% to 50%, grade III as 51% to
75%, and grade IV as greater than 75%.25 Shahian offered an interesting
and detailed classification scheme. In this classification scheme, type I
substernal goiter is associated with anterior mediastinal extension; type
IA involves “isolated” anterior mediastinal disease, whereas type IB
involves “extensive” substernal involvement. Type II involves posterior
mediastinal involvement, with type IIA being an isolated posterior
mediastinal goiter, type IIB being a posterior mediastinal goiter with
ipsilateral extension relative to the thyroid lobe of origin, and type
IIC being a contralateral extension relative to the thyroid lobe of origin,
with C1 being retrotracheal and C2 being retroesophageal.26,27
54 SECTION 2 Benign Thyroid Disease

TABLE 6.1 Substernal Goiter Classification

Type Location Anatomy Prevalence Approach, Comment
I Anterior mediastinum Anterior to great vessels, trachea, RLN 85% Transcervical (sternotomy only if intrathoracic
goiter diameter > thoracic inlet diameter)
II Posterior mediastinum Posterior to great vessels, trachea, RLN 15% As above; also consider sternotomy or right
posterolateral thoracotomy if type IIB
IIA Ipsilateral extension
IIB Contralateral extension
B1 Extension posterior to both trachea and
esophagus
B2 Extension between trachea and esophagus
III Isolated mediastinal goiter No connection to orthotopic gland; may <1% Transcervical or sternotomy
have mediastinal blood supply

RLN, recurrent laryngeal nerve.

Fig. 6.1 Patient with a large cervical and substernal goiter. Substernal goiter extends into the left chest and then
crosses retrotracheally into the right chest, extending between the trachea and esophagus (substernal goiter
type IIB2). A, Right superior pole extends beneath the sternocleidomastoid muscle to the level of the mandible.
B, At the level of the cricoid cartilage, goiter is present bilaterally in the neck.

anteriorly and splaying the great vessels anteriorly. The mass then
comes to rest in a space posterior to the innominate vein, carotid sheath
contents, innominate and subclavian arteries, RLN, and inferior thy-
roid artery.26,27,30 It is important to know that the relationship of the
mass and the RLN is reversed compared with the normal cervical
orthotopic gland-RLN relationship. The RLN is ventral to the inferior
component of the mass and, if not recognized early on, can be stretched
or cut by even the most meticulous thyroid surgeon. The nerve can also
be entrapped between components of the posterior mediastinal goiter;
even in these circumstances, a portion of the goiter will be deep to the
RLN. Such posterior mediastinal goiters can come to rest in a space
bounded inferiorly by the azygous vein; posteriorly by the vertebral col-
umn; laterally by the first rib; medially by the trachea and esophagus;
and anteriorly by the carotid sheath, subclavian and innominate vessels,
superior vena cava (SVC), and phrenic and RLNs.26,27
Posterior mediastinal goiter (type IIA) can occur ipsilateral to the
cervical gland of origin or may come to rest through retrotracheal
extension in the contralateral thorax (substernal goiter type IIB; see
Table 6.1). Extension to the right thorax is more commonly seen as
a result of aortic arch and is associated branch vessels obstructing
the left posterior mediastinal descent pathway.31,32 Contralateral tho-
racic extension in the posterior mediastinum may occur either behind
the trachea and esophagus (IIB1) or between the trachea and esophagus
(IIB2). Axial CT scanning and barium swallow help determine this
pattern. Generally, the right thoracic caudal extension is limited at
the level of the azygous arch (Figure 6.1).33
ISOLATED MEDIASTINAL GOITER (SUBSTERNAL
GOITER TYPE III)
Although rare, thyroid masses within the mediastinum may exist with-
out connection to the normal cervical orthotopic gland. Such purely
isolated mediastinal goiters represent only 0.2% to 3% of all goiters
requiring surgical treatment.11,24,34,35 Such lesions are important to rec-
ognize because unlike all other types of substernal goiters, the blood
supply of the isolated mediastinal goiter may be provided through
Fig. 6.1, cont’d See legend on next page.
56 SECTION 2 Benign Thyroid Disease

purely mediastinal arteries (including the aorta, subclavian, internal
mammary, thyrocervical trunk, and innominate) and veins. This is
extremely important when planning surgical resection.11,24,36-40 This
entity is best termed isolated mediastinal goiter. Other terms
have been used, including aberrant mediastinal and ectopic mediastinal
goiter.
Please see the Expert Consult website for more discussion of
this topic.
PREVALENCE, PATHOGENESIS, AND NATURAL
HISTORY
Prevalence
Multinodular goiter affects 4% of the United States’ population and up to
10% of the British population.45,46 New thyroid nodular disease occurs in
0.1% to 1.5% of the general population per year.47,48 Globally, iodine defi-
ciency contributes to the vast majority of cases of multinodular goiter and
was estimated to affect 1.5 billion people, or nearly 30% of the world’s pop-
ulation in 1990.49 Further, it is estimated that approximately 655 million
people in 118 countries are affected by endemic goiter. Endemic goiter
regions are defined as iodine-deficient regions in which at least 5% to
10% of the population is affected by goiter. In certain iodine-deficient
regions, higher goiter rates occur. In 1994 in Bangladesh, approximately
47% of the population was affected by endemic goiter.50 The majority of
the natural iodine supply exists as iodide in the world’s oceans. It is therefore
mainly noncoastal mountainous and lowland regions—where iodine is lea-
ched from the soil by flooding, heavy rainfall, and deforestation—that are at
risk for endemic goiter. Sporadic forms of multinodular goiter do occur in
iodine-replete regions with lesser prevalence.16,49 Prevalence estimates of
sporadic goiters vary between authors, ranging from less than 4% (clinical
evaluation series) and between 16% and 67% (ultrasound series).51,52
Please see the Expert Consult website for more discussion of
this topic.
Pathogenesis
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Natural History
The natural history of untreated, sporadic, nontoxic goiter is not
completely understood, but slow growth appears to be the general pre-
dictable pattern. Berghout et al. suggested a steady volume increase of up
to 10% to 20% per year.75 Pregnancy, iodine deficiency, consumption of
goitrogens, and alteration in suppressive or antithyroid medical regimens
can result in goiter progression. Hemorrhage into a preexisting nodule
can also result in the development of acute, regional, and airway symp-
toms.76 In patients presenting with diffuse goiter, there is a general ten-
dency toward nodule formation and progressive autonomy, with
hyperthyroidism ultimately developing in up to 10% of patients (see
Chapter 8, The Surgical Management of Hyperthyroidism).77
Please see the Expert Consult website for more discussion of
this topic.
CLINICAL PRESENTATION
Cervical Goiter
History
The history of goitrous growth and associated symptoms is critical for
determining surgical candidacy. This history should be obtained not
only from the patient but also from the patient’s family. Regional
symptoms should be addressed relating to respiration, phonation, swal-
lowing, and the presence of globus (lump sensation). As Pemberton
emphasized in 1921, symptoms associated with goiter may be position-
ally induced.38 Positions that may provoke goiter regional symptom-
atology include being supine, arms raised (as when reaching for an
upper cabinet), extreme neck extension, extreme neck flexion (as with
reading a book in bed), and turning the head to the extreme left or right.
Patients thus need to be questioned about positional provocation of
regional symptoms. In addition, the family needs to be questioned
about nocturnal symptoms, because symptoms may manifest initially
in the setting of recumbency and upper airway relaxation during sleep.
Symptoms may also be associated with exercise and increased oxygen
demands. A history of preceding upper respiratory tract infection may
produce dyspnea in a patient with long-standing tracheal obstruction
secondary to goiter through new laryngotracheal mucosal edema.
Patients with cervical or substernal goiter may present with cough, dys-
pnea, foreign-body sensation, neck tightness, change in collar size, or
wheezing and may come to the head and neck surgeon with a misdiag-
nosis of asthma or chronic obstructive pulmonary disease (COPD). In
our series of patients with large cervical and substernal goiter, we found
that 25% of patients were preoperatively asymptomatic.12
Symptoms of hypothyroidism and hyperthyroidism should be
reviewed. Hyperthyroidism may slowly evolve in patients with multi-
nodular goiter or may develop acutely in response to significant iodine
load such as with a CT scan contrast (Jod-Basedow phenomenon) or
with the introduction of iodized salt in endemic goiter regions.82 A his-
tory of migration from an area of endemic goiter should be obtained, as
well as a history of exposure to known goitrogens, notably iodine and
lithium. A family history of thyroid disease should also be obtained.
Physical Examination
After documentation of thyroid size, the examiner should note the con-
sistency and fixation of the mass, especially with respect to the larynx
and trachea. Estimation of goiter size by physical examination is clearly
an inaccurate method of assessment. Jarlov et al. found substantial
errors in the clinical assessment of thyroid size compared with ultraso-
nographic assessment.83 Estimated weight based on the physical exam-
ination generally underestimates multinodular goiter weight by 25 to
50 g.47 The larynx (landmarks include thyroid notch and cricoid ante-
rior arch) and trachea should be examined for deviation from the mid-
line. Typically, cervical goiter will deviate the larynx and trachea to the
contralateral side. Inability to palpate the lower thyroid lobe edge
should raise suspicion for substernal extension and prompt additional
evaluation. The neck must also be examined for adenopathy as well as
scarring from past thyroid and other neck surgery. Jugular distention

Fig. 6.1, cont’d C, At the level of the thoracic inlet, the left lobe expands and extends into the left chest and retrotracheally into the right thorax. D, The
mass extends substernally along the left lateral trachea and retrotracheally, abutting both left and right lung fields, splaying the great vessels. E, The distal
segment of the substernal mass has several lobulations. The innominate artery is seen anterior to the trachea. A bronchus abuts the lateral aspect of the
inferior-most goiter segment. The goiter posteriorly abuts the vertebral column. F, The inferior-most extent of the goiter extends retrotracheally deep to
the level of the aortic arch. The mass can be seen infiltrating the region between the trachea anteriorly and the esophagus posteriorly. G, The mass
extends between the trachea and esophagus, ending just above the azygous vein and right mainstem bronchus. H, Barium swallow showing substantial
cervical and mediastinal esophageal deviation. The mass was resected transcervically without sternotomy, with recurrent laryngeal nerve and vagal
monitoring with normal cord motion postoperatively. The specimen weighed 450 g and was 15 cm in greatest diameter.
56.e1

Three explanations exist for isolated mediastinal goiter. Embryologic

fragmentation of thyroid anlagen with hyperdescent, likely associated
with cardiac and great vessel descent, may explain some cases of iso-
lated mediastinal goiter (see Chapter 5, Thyroglossal Duct Cysts and
Ectopic Thyroid Tissue, and Chapter 9, Reoperation for Benign Thy-
roid Disease).41,42 Alternatively, isolated mediastinal goiter may form
as an exophytic nodule through progressive attenuation of the
nodule-thyroid stalk.41,43,44 Finally, the isolated mediastinal goiter
may form as a parasitic nodule representing a thyroid tissue fragment
implant in the upper mediastinum from past goiter surgery. We have
seen such implants also within the perithyroid area and posterior to the
upper cervical segment of the carotid artery.
 56.e2

Based on tuberculosis screening radiography in Australia and the

United States, substernal goiter has been estimated to be present in
0.02% of the general population and 0.05% of females older than
40 years.53,54 The incidence of substernal goiter was found to signifi-
cantly increase with age, with 60% of substernal goiters occurring in
patients older than age 60 years.53 Rates of substernal goiter in the past
several decades appear to be decreasing, perhaps related to the intro-
duction of iodized salt, thyroid hormone suppressive therapy, radio-
iodine use in selective cases, and perhaps more sensitive detection
and earlier intervention.2,55 Substernal goiter, as a percentage of
patients undergoing thyroidectomy, ranges from less than 1% to greater
than 20%, depending on the series, with most suggesting a rate of
approximately 10%.11,17,18,27,56-60 Substernal goiters represent approx-
imately 5% of all mediastinal tumors.27,61
56.e3
Pathogenesis
The pathogenesis of goiter formation has classically relied on the notion
that iodine deficiency promotes persistent elevated thyroid-stimulating
hormone (TSH) levels, inducing diffuse thyroid enlargement through
thyrocyte proliferation. Nodules form in the enlarged thyroid as the
patient ages, eventually giving rise to multinodular goiter.62,63 Since the
early 2000s, this classic model has been challenged by the view that the
thyroid gland has an intrinsic propensity to form nodules over time. In
this new model, low iodine levels and elevated TSH are considered addi-
tional factors, exacerbating the innate process of nodule formation.64,65
The shift in conceptualization of goiter pathogenesis has stemmed
from new cellular models, first proposed by Studer and Derwahl.64-67
These authors have argued that the development of multinodular goi-
ter, at least in the later stages, is independent of TSH levels. Nodules
arise because thyroid follicles are embryologically derived from
polyclonal progenitors and thus have a heterogeneous sensitivity to
TSH signaling.68 Similarly, thyroid follicles have a differential growth
response to continuous exposure to goitrogens, explaining the multi-
nodular pattern of goiters. In addition, thyrocytes may undergo somatic
mutations and acquire a distinct growth capacity.69-71 There is some
suggestion that oxidative stress (caused by iodine deficiency, smoking,
or thyroid hormone synthesis) may lead to DNA damage, causing an
increase in the spontaneous mutation rate and leading to tumorigene-
sis.72 The contribution of somatic mutations in multinodular goitro-
genesis remains, however, somewhat controversial. This is in
contrast with rare growth-promoting germline mutations of the TSH
receptor gene, which are believed to be pivotal in congenital diffuse goi-
ter with hyperthyroidism.73 Importantly, activating mutations in the
TSH receptor gene have not been associated with an increased risk
of malignancy.74

Most substernal goiters arise in the setting of preexisting cervical goiter.
It is of note, however, that some patients with substernal goiter have no
significant cervical goiter component. Substernal goiters virtually
always have a connection to the cervical orthotopic gland. Lahey, in
his vast experience of approximately 24,000 goiter surgeries, believed
that all substernal goiters arise from the cervical gland and maintain
their cervical blood supply.78 Even in cases of extreme substernal goiter
extending to the diaphragm, the mediastinal component has been
found to contain connections to the cervical gland and a blood supply
from the inferior thyroid artery.79-81 Connection to the cervical gland
may be robust or attenuated, but it virtually always exists. The work of
Torre, based on an impressive series of 237 substernal goiters, suggests
that substernal goiters arise 10 years after cervical goiter presentation,
suggesting that substernal goiter evolves from preexisting cervical goi-
ter in most cases.8
56.e4
The inferior extension of cervical goiter and formation of substernal
goiters are poorly understood. The inferior descent relates in part to the
pattern of nodular disease within the cervical gland. Inferior progres-
sion results from a limitation of the strap muscles anteriorly, trachea
medially, and vertebral column posteriorly. As Lahey and Swinton have
described, the neck is “a space with no bottom.”17 The repetitive forces
of deglutition, respiratory dynamics, negative intrathoracic pressure,
and gravitational forces in the setting of permissive mediastinal and
neck base fascial planes facilitate the downward extension of cervical
goiter. Typically, anterior mediastinal extension (substernal goiter type
I) occurs from the ipsilateral lobe’s inferior expansion. Descent associ-
ated with significant retrotracheal posterior mediastinal extension may
arise from more posterior elements of the thyroid gland such as poste-
rior tubercles of Zuckerkandl (see Table 6.1).
 CHAPTER 6 Surgery of Cervical and Substernal Goiter
and subcutaneous venous redistribution should be noted. Although
both of these may be present with large benign cervical or substernal
goiter, true SVC syndrome is generally due to malignant thyroid disease
and warrants careful scanning and evaluation.11
It is imperative in all patients with goiter that the larynx be exam-
ined. In our series, we have found that 2% of patients with goiter pre-
sented with vocal cord paralysis in the setting of benign disease and no
prior neck surgery, and 3.5% of preoperative patients presented with
goiter overall.12 Vocal cord paralysis without a history of past thyroid
surgery implies invasive thyroid malignancy until proven otherwise. It
should be noted, however, that benign goiter may also be associated
with vocal cord paralysis, presumably through stretching of the nerve,
which may recover postoperatively (see Chapter 36, Surgical Anatomy
and Monitoring of the Recurrent Laryngeal Nerve).84 Certainly, such a
preoperative finding focuses the surgeon’s attention on the extreme
importance of preserving the contralateral RLN. The laryngeal exami-
nation in patients with large cervical goiter can be difficult if there is
edematous or redundant supraglottic mucosa, laryngeal compression
and deviation, and hypopharyngeal crowding resulting from goitrous
extrinsic compression. Symptomatic assessment of the voice, like
symptomatic assessment of the airway, does not predict objective find-
ings in patients with goiter and should not replace the laryngeal exam-
ination. In our patient series, voice change was reported preoperatively
in 12.8%, but vocal cord paralysis was present in only 3.5%, consistent
with the work of Michel, emphasizing that glottic function cannot be
predicted by voice assessment.85,86 Michel, in his series of substernal
goiters, noted that although hoarseness was described in 26%, vocal
cord paralysis was only found in 3%.87 Thus, we reiterate our recom-
mendation that all patients with goiter undergo preoperative laryngeal
examination.
Substernal Goiter
Please see the Expert Consult website for more discussion of this topic.
GOITER WORKUP
During the workup of patients presenting with a goiter, the clinician
should address the following three important issues: (1) the existence
or the potential development of airway compression, (2) the risk of malig-
nancy, and (3) the presence of hyperthyroidism (Boxes 6.1 and 6.2).
Airway Assessment in Thyroid Disease
Foremost in goiter assessment is airway evaluation. The fundamental
components of airway evaluation include determination of the rate
and pattern of respiration, presence of sound with breathing (i.e., stri-
dor), and voice quality. In patients with significant airway obstruction
from thyroid disease, the initial assessment requires integration of a tar-
geted but complete history and physical examination to expeditiously
identify the site and magnitude of obstruction. One must always
remember to keep in mind the overall global status of the patient with
respect to his or her respiratory effort and signs of distress. Fatigue,
restlessness, or apprehension can occur in the setting of hypoxia.
The patient who is lethargic may be hypercapnic. Body position as
an indicator of respiratory comfort, peripheral signs of oxygenation,
and cyanosis should be carefully evaluated. Included in this assessment
is the taking of vital signs and the use of pulse oximetry. One must be
vigilant that a patient with a good pulse oximeter reading—or, for that
matter, good arterial blood gas levels—may, a moment later, experience
complete respiratory obstruction. The sound of respiration (i.e., the
presence of stridor) gives an important clue as to the magnitude and
location of airway obstruction. Stridor implies turbulent airflow
through a stenotic airway segment. Significant extrathoracic
57
BOX 6.1 Airway Imaging, Flow Volume
Loops, and Goiter Symptoms: Summary
• The presence of preoperative shortness of breath correlates with goiter size,
but it is of limited value as a screening tool for tracheal abnormalities.
• Dysphagia correlates with radiographic findings of esophageal deviation
and compression. In the absence of dysphagia, patients do not require fur-
ther esophageal imaging.
• Symptomatic assessment of voice does not predict objective findings in
patients with goiter and should not replace the laryngeal examination.
• Flow volume loop studies most accurately document airway obstruction in
the setting of significant airway compression. However, they correlate
poorly with goiter weight and upper airway symptoms. We do not recom-
mend flow volume loop studies as part of the routine workup for patients
with goiter.
• Axial computed tomography (CT) scanning is recommended for large cervical
and substernal goiters, because it provides a more sensitive airway assess-
ment than patient symptomatic, flow volume loop, and plain film analysis.
The finding of tracheal compression on axial CT scanning correlates signif-
icantly with the presence of shortness of breath; therefore we consider the
finding of CT scan tracheal compression to be an appropriate surgical indi-
cation given its symptomatic respiratory correlate.
BOX 6.2 Workup for Benign Goiter
History and physical examination
Symptomatic*
Massive goiter*
Bilateral circumferential goiter*
Suspect substernal goiter*
Suspect cancer (vocal cord paralysis, lymphadenopathy)*
Ultrasound to evaluate for suspicious nodules
Thyroid function tests
*Obtain CT or MRI.
CT, computed tomography; MRI, magnetic resonance imaging.
obstruction (most commonly laryngeal, subglottic, or upper cervical
tracheal) typically presents with inspiratory stridor and is seen as a
variable extrathoracic obstruction on flow volume loop analysis with
inspiratory phase flattening. Isolated expiratory stridor is seen in intra-
thoracic (lower tracheal) obstruction. Here, inspiration is silent and the
voice is normal.
Acute Airway Compromise
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including Figure 6.2.
EVALUATION OF UPPER AIRWAY COMPROMISE
AND OTHER REGIONAL SYMPTOMS
Regional Symptomatic Assessment
Upper airway obstruction is a common finding in patients with goiter,
highlighting the importance of optimal airway evaluation. Common
presenting symptoms in our series of patients with goiter included
shortness of breath (approximately 50%) and dysphagia (approxi-
mately 50%), emphasizing the effect of cervical and substernal goiter
on the adjacent cervical viscera. Although earnest symptomatic
assessment at presentation is crucial in patients with goiter, clinical
experience suggests subjective symptomatic assessment of the upper
57.e1
Substernal Goiter
In many ways, the history and physical examination for patients with
substernal goiter significantly overlaps with those for patients with cer-
vical goiter. In our series we have found that as cervical goiter pro-
gresses substernally, given the restriction of the bony confines of the
thoracic inlet, it increasingly compromises the airway. In short, subster-
nal goiter evolution is strongly correlated with tracheal deviation, the
development of regional airway symptoms, and radiographic airway
compression.12 Buckley and Stark noted that although the maximum
tracheal deviation with substernal goiter usually occurs at the thoracic
inlet, it may occasionally occur farther inferiorly.33 Larger surgical
series of substernal goiter show 70% to 80% of substernal goiter patients
are symptomatic at presentation. Cervical mass is noted in 69% to 97%,
respiratory symptoms in 42% to 96%, dysphagia in 26% to 60%, and
acute airway presentation in 1% to 5% of patients.2,8,11,19,20,25,56,88-93
Interestingly, these series show that 10% to 30% of substernal goiter
patients, as previously noted, have no significant palpable cervical
abnormality, 3% to 7% present with vocal cord paralysis, and 4% to
50% are asymptomatic at presentation. Wax and Briant have noted
that, with careful questioning, up to one-third of patients who are
“asymptomatic” admit to symptoms.92
Pemberton’s sign is described as the development of head and neck
venous engorgement with facial congestion, plethora, and venous
distention with arms raised over the head. It is sometimes expanded
to include the development of transient respiratory insufficiency. Pem-
berton’s sign is thought to indicate goiter extension into the thoracic
inlet, with secondary relative venous and airway obstruction.38,59,94
Our series of large cervical and substernal goiters suggests that Pember-
ton’s sign is insensitive in the evaluation of substernal goiter, because
only 4.4% of patients presented with a positive Pemberton’s sign.12 Sub-
sternal goiters can also present with neck and upper chest pain and have
rarely been associated with hematemesis secondary to downhill esoph-
ageal varices (without signs of portal hypertension), abscess formation,
Horner’s syndrome, chylothorax (secondary to thoracic duct obstruc-
tion), transient ischemic attacks through “thyroid steal syndrome,”
venous thrombosis, and intubation injuries, especially to the posterior
tracheal membranous wall.57,95
Laryngeal shift to the side of a dominant cervical goiter suggests con-
tralateral substernal goiter and requires axial imaging of the neck and
chest. Similarly, laryngeal shift without any palpable cervical findings sug-
gests substernal goiter and similarly requires axial neck and chest imag-
ing.11,19,82,88,96 Finally, substernal goiter is suspected when the clavicle
intervenes before the inferior extent of the thyroid mass can be palpated.

Acute Airway Compromise
The frequency of development of acute airway compromise in cervical
and substernal goiter varies depending on the population studied.
Unfortunately most of the information available is from surgical series.
Allo and Thompson have estimated that from 1% to 3% of patients with
untreated mediastinal goiter die of respiratory obstruction.56
The airway can be affected by goiter through a number of mecha-
nisms, including, most typically, ongoing slowly progressive airway
deviation and compression. Acute events can also precipitate airway
compromise, including hemorrhage into a nodule of multinodular goi-
ter. Georgiadis has described acute stridor caused by hemorrhage
within a nodule after neck trauma.97 Pulli and Coniglio have described
a patient whose goiter increased in size after a fall on ice.2 Torres et al.
have presented a number of cases showing acute life-threatening tra-
cheal obstruction in patients with long-standing, intrathoracic goiter
with subsequent histology showing multiple foci of recent hemor-
rhage.98 Hemorrhage as a mechanism of goiter size increase is sup-
ported by the work of Bodon and Piccoli.99 We have seen acute
tracheal obstruction with magnetic resonance imaging (MRI) scan evi-
dence of central nodular hemorrhage in what was ultimately found to
be a large benign follicular adenoma (Figure 6.2). Sudden airway symp-
toms may also arise as a result of cystic degeneration, malignant degen-
eration, upper respiratory tract infection, or pregnancy.100 Rare
mechanisms for respiratory distress in patients with large goiters
include decompensated right heart failure, pleural effusion, and pulmo-
nary hypoperfusion secondary to compression of the pulmonary arter-
ies.94 We agree with Cougard et al. that a patient with goiter and acute
airway decompensation requiring endotracheal tube intubation should
be brought to surgery when stable and while intubated. Ultimately, after
thyroid surgery a laryngeal examination should be performed to rule
out laryngeal edema and assess vocal cord function before
extubation.101
Fig. 6.2 A, A patient with hemorrhage within a benign follicular adenoma with sudden enlargement and sudden onset airway deviation and compression
with respiratory symptoms. Note that the tracheal air column is substantially deviated to the left and that on plain chest radiograph, no significant com-
pression is appreciated. B, Magnetic resonance imaging axial scanning shows substantial airway compression. Note the density within the center of the
thyroid mass that represents hemorrhage.
57.e2
Miller et al., in a nonsurgical series of 400 patients with goiter, eval-
uated patients with pulmonary function tests and flow volume loops.
Nearly one-third of such patients had flow volume evidence of upper air-
way obstruction.9 Gittoes et al., in a study of 153 goiter patients followed
in a medical/endocrine clinic, also found that 33% of such patients had
evidence of upper airway obstruction on flow volume loop analysis.45
Thus two large nonsurgical series suggest that up to one-third of patients
with large goiters followed in endocrine clinics have evidence of upper
airway obstruction as defined on flow volume loops. Limited data are
available within this population as to the rate of development of acute
airway symptoms. Alfonso found, in a surgical series of 91 patients with
benign goiters with either radiographic or symptomatic evidence of
upper aerodigestive tract compression, that approximately 9% of patients
presented with acute upper airway obstruction.102 Reeve, Rubenstein,
and Rundle, in a large screening radiographic study that identified
patients with significant thyromegaly as defined by plain radiographs,
found 7.6% of such patients presented with “profound respiratory
obstruction.”53 In a surgical series of patients with substernal goiter,
reports vary, with 1.3% to 5% of such patients presenting with acute air-
way insufficiency.11,25,56,88,89,96,103,104 Higher rates of acute airway insuf-
ficiency have been reported in other surgical series.90,105
Thus approximately one-third of patients with goiter in medical
series have upper airway obstruction as defined by flow volume loops,
and from 1.3% to 9% of such patients may present with acute airway
symptomatology. Unfortunately, a long, chronic, stable history does
not preclude spontaneous acute airway insufficiency.56 Warren has
beautifully documented cases of acute respiratory failure secondary
to goiter in elderly patients. All presented with acute respiratory col-
lapse without a history of respiratory symptoms 48 hours before the
respiratory failure.104 Cho, Cohen, and Som also emphasized, in a
review of 70 patients with substernal goiter, the potential for sudden
and unpredictable respiratory distress.25
57.e3
There is sometimes a tendency to follow up patients with large com-
pressive goiters with flow volume loops and symptomatic assessment.
There is no evidence to suggest this is a rational approach. It is known
that flow volume loops begin to detect airway obstruction when tra-
cheal diameter is reduced to an extremely limiting 5 mm.106 Symptoms
of acute airway insufficiency may not occur until up to 75% of the tra-
cheal lumen is obstructed.98,107 At our institutions, serial axial CTs are
recommended to determine surgical candidacy, most typically by doc-
umenting substernal extension or tracheal compression.12 We have
found that regional signs and symptoms, such as upper airway obstruc-
tion or radiographic evidence of tracheal or esophageal compression,
are more likely with masses larger than 5 cm. Also, fine-needle aspira-
tion (FNA) represents a less accurate assessment with lesions of this size
compared with thyroid nodules between 1 and 3 cm.
58 SECTION 2 Benign Thyroid Disease

aerodigestive tract compressive symptoms in patients with goiter can be Chest Radiography and Barium Swallow Study
quite problematic. Although we found that the presence of shortness of Please see the Expert Consult website for more discussion of this topic.
breath correlates with goiter size, shortness of breath as a screening tool
for tracheal deviation or compression is of limited value. This is despite
Axial CT Scanning
the fact that the presence of shortness of breath is significantly related to
We have found routine CT scanning to be very helpful in preoperative
the imaging finding of tracheal compression, consistent with the work
assessment of patients with large cervical or substernal goiters.12,121 CT
of Mackle.108 Stang et al. also reported a strong association between
with iodinated contrast may be performed safely (i.e., without the Jod-
positional dyspnea and substernal goiter (75.5%), with significant cor-
Basedow phenomenon) in patients with thyroid disease if thyroid-
relation with tracheal compression on axial CT imaging.109 However,
stimulating hormone (TSH) is not found to be suppressed. CT scanning
for the airway, symptomatic assessment alone may be inadequate over-
shows the margin of benign goiter to be smooth and may often delin-
all in goiter patients. In the setting of large cervical or substernal goiter,
eate gross calcification (which may be punctate, linear, eggshell, amor-
one cannot purely rely on the presence or absence of shortness of breath
phous, or nodular) versus the fine stippled microcalcification that may
to assess true tracheal compromise without routine axial CT scanning
be present in papillary or medullary carcinoma (see Chapter 13, Ultra-
assessment for tracheal compression. In our series there was no signif-
sound of the Thyroid and Parathyroid Glands). In patients with sub-
icant difference in the percentage of patients with airway symptoms
sternal goiter, continuity of the mediastinal mass and cervical
between patients with purely cervical goiter and patients with subster-
orthotopic gland can be identified. Precontrast attenuation of thyroid
nal goiter. However, in our series, substernal goiter was highly associ-
tissue exceeds adjacent neck musculature by at least 15 Hounsfield
ated with tracheal deviation and compression.12
units or greater and by more than 25 Hounsfield units after contrast
Our series also demonstrated a positive correlation between thyroid
enhancement. In patients with substernal goiter, this high attenuation,
size, globus sensation, and symptoms of hyperthyroidism. No correla-
which is uncharacteristic in other types of mediastinal disease such as
tion was established between goiter size and presence of dysphagia,
lymphoma or thymoma, can be helpful diagnostically.33,122 With CT
local discomfort, change in voice, hemoptysis, or symptoms of hypo-
scanning, the extent of cervical and substernal extension can be accu-
thyroidism. There was a significant positive correlation between preop-
rately defined, and the exact relationship of the goiter to the trachea,
erative dysphagia and the presence of esophageal compression and
esophagus, and great vessels can be determined. The presence of nodal
deviation.12 Hedayati and McHenry reported that about one-third of
disease can also be established through axial scanning. Generally,
116 patients undergoing surgery for substernal goiter complained of
benign goiter shows heterogeneous density with discrete nonenhancing
dysphagia on initial presentation.110
low-density areas. Malignancy may be considered in the setting of
radiographic findings of irregular/infiltrative margins, vocal cord paral-
Flow Volume Loop Analysis ysis, and nodal enlargement, especially if the nodes are calcified, cystic,
Please see the Expert Consult website for more discussion of this topic. or enhancing.123-125 Contrary to McHenry’s view that preoperative
radiographic evaluation does not alter intraoperative management,
Imaging we believe that CT scanning is essential for all patients with large cer-
vical and substernal goiters.7 We are more likely to obtain CT scanning if
Radiographic Evaluation and Regional Symptomatology
the clinical examination suggests that the goiter is large, symptomatic,
A number of studies question the strength of the correlation between
bilateral, or substernal or if malignancy is suspected based on vocal cord
regional symptoms and imaging study findings. In particular, the func-
paralysis or regional lymphadenopathy (see Box 6.2). CT scanning ide-
tional effect of airway narrowing diagnosed via CT scan remains con-
ally shows the relationship of the goiter to surrounding cervical viscera,
troversial. Alfonso et al. found that two-thirds of surgical goiter patients
including the airway. These relationships can affect not only surgery but
had preoperative radiographic evidence of compression. Almost half of
also the approach to intubation. Axial CT provides objective, reproduc-
those patients with evidence of compression had no symptoms. Those
ible measures of tracheal caliber. A patient’s surgical candidacy may
patients with airway symptoms who had old radiographs available for
derive from information obtained from axial CT scanning, especially
comparison were found to have compression up to 3 to 4 months before
given a lack of sensitivity of symptoms, flow volume loop analysis,
the onset of airway symptoms.102 Jauregui found in a series of asymp-
and plain radiographic assessment. At our institutions, documentation
tomatic euthyroid goiter patients that 25% had radiographic evidence
of substernal extension or tracheal compression on CT is an appropriate
of tracheal obstruction and 60% had evidence of airway obstruction by
surgical indication.12 CT scanning also provides helpful information to
flow volume loops.114 Cooper et al. found that tracheal diameter and
exclude invasive malignancy. It is true that CT scanning does not
airway symptoms are weakly related.115 Melissant and others have
differentiate well between fibrosis and tumor, although this distinction
found little correlation between lung function and the CT scan–defined
is generally not a significant clinical issue for routine goiter patients.
degree of tracheal obstruction.111,116
Finally, enhanced CT scanning is essential in determining the mediasti-
Conclusions from our series stand in contrast with the previously
nal relationships to allow safe operative management for large posterior
mentioned literature. As noted earlier, we found a significant correla-
mediastinal goiters. Identification of significant retrotracheal extension
tion between the presence of shortness of breath and the objective CT
of either cervical or substernal goiter helps in predicting preoperatively
scan radiographic finding of tracheal compression.12 Stang et al. found
that the RLN is displaced to a ventral position. Preoperative information
a high correlation of tracheal compression on imaging with positional
of ventral nerve displacement is tremendously helpful in the offering of
dyspnea and further showed postsurgical improvement of symptoms in
safe cervical and substernal goiter surgery (Box 6.3).
82.4% of cases.109 Barker et al. similarly noted that if the CT scan
showed greater than or equal to 50% tracheal diameter narrowing,
MRI Scanning
symptoms should be expected.117 We therefore consider tracheal com-
pression to be an important radiographic finding and an appropriate Please see the Expert Consult website for more discussion of this topic.
surgical indication in these patients (see Boxes 6.1 and 6.2).
Please see the Expert Consult website for more discussion of Sonography and Scintigraphy
this topic. Please see the Expert Consult website for more discussion of this topic.

Flow Volume Loop Analysis
Although symptomatic assessment is important in patients with cervi-
cal and substernal goiter, the relationship between such symptoms at
presentation and pulmonary function evaluation is problematic. Flow
volume loops have been used to define airway compromise in goiter
patients. In our centers, flow volume loop analysis is not part of the rou-
tine workup for goiter. Goiter weight is not well correlated with flow
volume loop results.9,45 Bonnema has also reported that overall flow
volume loop results do not correlate well with tracheal caliber on axial
CT.111 Only 30% to 40% of those with flow volume loop abnormalities
have symptoms, and among those with normal flow volume loops, up
to 60% may have airway symptoms.
This discordance between flow volume loop results and symptoms
or objective axial CT scan findings in goiter patients should not be
58.e1
surprising. It is well known that lung function indices are inconsistently
related to tracheal size in normal subjects.112,113 Poiseuille’s law (flow
proportional to radius) implies that with a significant reduction in the
tracheal airway, small changes in tracheal caliber will be reflected in sig-
nificant changes in flow volume loop characteristics, but with lesser
degrees of tracheal narrowing, the two variables are more weakly
related. In fact, it is known clinically that tracheal compression of up
to 75% of the tracheal lumen may occur without clinical manifesta-
tion.9,98 Flow volume loop studies can detect tracheal stenosis when tra-
cheal diameter is less than 5 mm, but it may not be affected in less
severely narrowed airways.106 Flow volume peak inspiratory flow of less
than 1.5 L has been associated with a high risk of acute respiratory fail-
ure and has therefore been used as an indication for urgent
thyroidectomy.9,98,102
58.e2

The relationship between esophageal symptoms and abnormal barium

swallows is less contested. Alfonso et al. found that out of 273 patients
with benign thyroid diseases 25 patients had dysphagia and all 25
patients also had abnormal barium swallow exam.102 In our series, dys-
phagia was significantly associated with both radiographic esophageal
deviation and compression, as evaluated with barium swallow studies.
The absence of dysphagia was associated in our series with a negative
predictive value of 96% for esophageal compression.12 We therefore con-
sider that patients without dysphagia likely do not have esophageal
involvement and do not require further esophageal imaging (see
Box 6.1.)

Chest Radiography and Barium Swallow Study
Chest radiography preoperatively provides limited information regard-
ing tracheal air column and may allow detection of macronodular pul-
monary metastasis in patients with thyroid enlargement. Chest
radiographs may reveal cervical or mediastinal densities with or with-
out calcification and may, with substernal extension, identify a plane of
reflection of the mediastinal pleura. Chest radiographs are read as
abnormal in up to 40% to 90% of patients with substernal goi-
ter.11,22,57,86,91,118 Several researchers have noted that tracheal diameter
as estimated from plain films is significantly greater than tracheal diam-
eter as measured on CT scans, axial studies, or in cadaveric stud-
ies.117,119 Melissant et al. found that plain films missed significant
tracheal obstruction in 50% of patients.116 Cooper et al. also found
in a review of cervical and substernal goiter patients that plain films
were misleading in 48% of patients, resulting in both over- and under-
estimation of tracheal narrowing compared with CT axial scanning.115
Plain chest radiographs can be especially misleading in the rare poste-
rior mediastinal goiter with contralateral extension retrotracheally with
respect to the lobe of origin (substernal goiter type IIB). Tracheal
58.e3
deviation in this complex circumstance may be toward the side of
the mass as seen on plain radiographs.26,27,120 We have also found that
a chest radiograph generally gives reasonable information regarding the
degree of tracheal air column deviation but significantly underestimates
tracheal compression (see Figure 6.2).12 In addition, when a goiter is
present bilaterally, it may symmetrically compress the airway without
any deviation. In such circumstances, axial CT scanning may reveal a
significantly compressed airway, yet a plain chest radiograph may fail to
show any distortion of the tracheal air column.
Barium swallow, although not generally helpful in the preoperative
evaluation of patients with cervical and substernal goiter, may be help-
ful in posterior mediastinal goiter. Michel found that sensitivity for the
identification of substernal goiter by chest radiograph was 59%, by thy-
roid scanning it was 77%, and with barium swallow it was 71%, empha-
sizing the inaccuracies of these modalities in goiter evaluation (see Box
6.2).86 Our recommendation is to not perform barium swallow studies
in the absence of dysphagia, because the presence of esophageal com-
pression is unlikely in asymptomatic patients.12
58.e4

MRI Scanning
We have found that CT and MRI scanning are more or less equivalent
in the assessment of cervical and substernal goiter. Several workers have
suggested that MRI may be superior to CT scanning with improved
vascular mediastinal relationships, ability for coronal display, and
potentially better detection of early tracheal and esophageal invasion
with less shoulder artifact.86,126,127 Disadvantages of MRI scanning
include respiratory induced motion artifact, cost, patient claustropho-
bia in nonopen MRI scanning suites, and poor definition of calcifica-
tion patterns.
 58.e5

Sonography and Scintigraphy

Thyroid sonography is usually the study of choice for evaluation of
gland architecture, identification and characterization of thyroid nod-
ules, and FNA of thyroid nodules.121 However, sonography is limited in
the workup of patients with large cervical or substernal goiters given the
inability to assess airway compression and substernal extent. Scintigra-
phy is not generally necessary. 131I and technetium scanning may be
helpful in cases of mediastinal mass without connection to the cervical
orthotopic gland. Also, in patients with toxic multinodular goiter,
iodine scanning can be helpful in mapping out hot regions, so that they
can be encompassed by surgery. In toxic multinodular goiter the sono-
graphic nodules may not necessarily overlie the areas of scintigraphic
activity. Thus iodine scanning may be helpful if less than total thyroid-
ectomy is planned (see Box 6.3).
 CHAPTER 6 Surgery of Cervical and Substernal Goiter
Thyroid Function Tests and Fine-Needle Aspiration
Thyroid function tests must be checked in all patients presenting with
goiter. In our series, only 8% of patients had noniatrogenic causes of
abnormal thyroid function testing, reaffirming that the majority of
patients with goiter, if not on suppressive therapy, are euthyroid.12
Nevertheless, rates of thyroid dysfunction in patients with goiter are
not negligible, and it is imperative that the clinician evaluates for
any abnormality. Hyperthyroidism is the foremost concern in patients
with goiter. Florid hyperthyroidism has been reported in up to 30% of
patients with multinodular goiter.77,128 Rates of hyperthyroidism in
patients with substernal goiter range from 1.3% to 7%, although rates
as high as 44% have been described.11,57,129 Autonomous nodules may
elicit a slowly progressive increase in thyroid hormone production
independent of TSH levels.130 Alternatively, hyperthyroidism may
manifest acutely in patients with goiter exposed to high iodine, such
as in CT scan contrast material or in amiodarone.131,132 Elderly patients
notoriously do not exhibit the typical overt signs and symptoms of
hyperthyroidism and are also more prone to cardiac complications.
Screening for subclinical hyperthyroidism (TSH low, T3 and T4 nor-
mal) is particularly crucial in the elderly population because of the
increased risks of atrial fibrillation and accelerated bone demineraliza-
tion. Subclinical hyperthyroidism may also inform the issue of extent of
surgery and may lead more toward total thyroidectomy if present. Iat-
rogenic iodine exposure should be avoided in elderly patients with sub-
clinical hyperthyroidism to avert the increased risk for the development
of overt hyperthyroidism.133,134 Finally, hypothyroidism (typically
Hashimoto’s disease) must also be excluded in patients with goiter.
A fibrotic variant of Hashimoto’s disease can result in a massive
firm goiter.
We believe that if the history, physical examination, and CT scan
evaluation of the patient with thyromegaly suggest benign goiter
requiring surgery and surgical candidacy is established on that basis,
then fine-needle aspiration (FNA) is not essential.2 Certainly, if there
is any suspicion on history, physical examination, or radiographic eval-
uation of malignancy, then FNA should be considered. The 2015 Amer-
ican Thyroid Association guidelines suggest consideration for FNA of
BOX 6.3 Imaging: Summary
• Plain chest radiography may detect macronodular metastatic disease but
generally offers limited information about the tracheal air column. Airway
compression is underestimated and bilateral goiter with circumferential tra-
cheal compression may not be well seen on plain radiographs.
• We recommend computed tomography (CT) scanning in all patients with
large cervical and substernal goiters. Axial CT scanning has the advantage
of being readily available and easily interpreted by the surgeon. CT scanning
is used to judge a patient’s surgical candidacy by accurately defining the
degree of tracheal impact. In patients with substernal goiter, CT scanning
informs surgical planning regarding sternotomy and potential thoracic sur-
gical involvement. CT scanning is helpful in identifying the radiographic cor-
relates of malignancy. It is also of tremendous importance in accurately
defining the anatomic relationships, especially in predicting when a recur-
rent laryngeal nerve (RLN) will be ventral through retrotracheal and posterior
mediastinal extension. Contrast should be avoided if the patient’s thyroid
functional status is unknown or if the patient is subclinically hyperthyroid.
• Advantages of magnetic resonance imaging (MRI) scanning are excellent
soft-tissue delineation, excellent definition of the goiter’s relationship to
mediastinal vessels, and sagittal and coronal display. Disadvantages of
MRI scanning include cost, patient claustrophobia in nonopen MRI scanning
suites, and poor definition of calcification patterns.
59
nodules
1 cm on an individual basis if they show moderate or high
suspicion sonographic pattern; FNA may be deferred for low suspicion
nodules and should be avoided for hot nodules.135 Hemorrhage into a
nodule after FNA may convert a stable but compromised airway into
emergency airway obstruction. FNA information infrequently contrib-
utes substantially to preoperative workup in patients with large cervical
and substernal goiters.
TREATMENT OPTIONS
Suppressive Therapy
Please see the Expert Consult website for more discussion of this topic.
Radioiodine
Please see the Expert Consult website for more discussion of this topic.
Surgery
Rationale and Indications
Surgery represents a rational treatment option for many patients with
cervical goiter and most patients with substernal goiter. Regional
compressive symptoms resolve postoperatively and faster than with
suppressive or radioiodine therapy. Complication rates are low, sub-
clinical hyperthyroidism remits, airway complications are avoided,
and a pathology report is provided. Goiter surgery is most safely offered
when it is not offered with undue delay. Waiting until a goiter is mas-
sive will likely increase operative complication rates. Surgery brings no
risk of radioiodine-induced immediate airway complications, malig-
nancies, or Graves’ disease. Surgery also brings no risk of thyroid
hormone-induced atrial fibrillation or osteoporosis. A patient cannot
be a “nonresponder” to surgery (Box 6.4). Surgery is recommended
in patients with multinodular goiter who present with hyperthyroid-
ism, because they do not generally respond well to antithyroid drugs,
including perchlorate and iopanoic acid.164 Furthermore, surgery
may be preferred over radioactive iodine treatment in elderly patients
with goiter and subclinical or frank hyperthyroidism, to forestall the
risk of radioiodine-induced Graves’ disease in this cardiac-frail popu-
lation (see Box 6.4).
Based on our experience, patients can be reasonably considered for
cervical goiter surgery in the following situations: (1) if a patient has
clear-cut regional upper aerodigestive tract symptoms without other
cause, often first manifesting with positional provocation or noctur-
nally; (2) if radiographic evaluation through axial CT scanning shows
evidence of tracheal compression; (3) for masses causing significant
BOX 6.4 Cervical and Substernal Surgery
Rationale
• Natural history of goiter is of progressive growth
• Treats existent regional/compressive symptoms
• Avoids rapid and unpredictable increase in size and airway compression
• Provides pathology report; rules out malignancy
• Treats hyperthyroidism and subclinical hyperthyroidism
• Has low operative morbidity
• Thyroid hormone (suppressive) treatment is associated with a high nonre-
sponse rate, requires lifetime treatment, cannot be offered if TSH is <1,
risks atrial fibrillation and osteoporosis, and is less likely to be effective with
large nodular goiters.
• Radioactive iodine treatment of goiter risks acute radiation thyroiditis and
airway compression and, in approximately 10% of patients, induces Graves’
disease.
TSH, thyroid-stimulating hormone.
59.e1
Suppressive Therapy
Reports about the effectiveness of thyroid hormone suppression in
nontoxic goiter suppression have varied greatly.27,136-139 In 1997 Lima
et al. prospectively studied thyroxine (T4) treatment at 200 μg to sup-
press TSH to less than 0.1 μU/L in patients with nontoxic multinodular
goiter. Responses defined as a greater than 50% decrease in combined
nodular volume occurred in only 29.1% of patients. Forty-seven per-
cent of patients were nonresponders.140 Berghout et al. found that in
patients responding to thyroid treatment, goiter size reduction aver-
aged only 25%. In addition, when thyroid hormone treatment was dis-
continued, thyroid volume was found to return to pretreatment values
within a few months.75 Hurley and Gharib found that thyroid hormone
was able to reduce goiter size by 50% in only 27% of patients.47 Ross
noted that when thyroid hormone is affected, a size reduction occurs
with a lag of approximately 3 months relative to initiation of therapy.136
Zorrilla found that thyroid hormone-induced size reduction was
unpredictable.141 Generally, diffuse goiters are thought to be more thy-
roid hormone responsive compared with multinodular goiters.136 Invo-
lution of normal thyroid tissue occurs more readily than pathologic
thyroid tissue with TSH suppression, limiting its use for large and mul-
tinodular goiters.121 Burgi et al. found that nodules larger than 2 or
3 cm are less likely to respond to thyroid hormone therapy.142 Other
studies looking at combined nodular volume reduction show response
rates ranging from 20% to 58% of patients suppressed.143-146
A study by Wesche et al. showed a >30% rate of thyrotoxic symp-
toms with T4 suppression in cases of sporadic nontoxic goiter.147 T4
suppression is generally not offered to patients who present with sub-
clinical hyperthyroidism with a TSH level less than or equal to 1 μU/L
or in elderly patients.47 Thyroid hormone suppressive therapy for goi-
ter, which must be carried out indefinitely because of the tendency for
goiter to recur after cessation of therapy, risks atrial fibrillation in
patients older than age 60 years and risks increased bone loss and oste-
oporosis, especially in postmenopausal women.133,148,149 Overall, a
review of the literature suggests that T4 suppressive therapy has vari-
able efficacy in reducing goiter size, is characterized by a high regrowth
rate of goiter when T4 is discontinued, and can be associated with
increased risk of thyrotoxic symptoms and decreased bone mineral
density.121,150,151

Radioiodine
Radioactive iodine therapy can be used for the treatment of nontoxic
multinodular goiter. Although not widely used in the United States cur-
rently, radioiodine as a treatment for large goiter with compressive
symptoms has become more commonplace in Europe. Higher doses
of 131I (similar to ablative doses used in thyroid cancer patients) are
required for nontoxic multinodular goiter, compared with doses used
for Graves’ disease, because of the large volume and lower uptake of
nontoxic multinodular goiters. Generally, uptake is lower in nontoxic
multinodular goiters than in diffuse (anodular) goiters (i.e., Graves’ dis-
ease).152 Recombinant human TSH has been used to enhance uptake in
nontoxic goiters, improve long-term outcomes, and reduce the
required radioiodine dose for treatment with some success.153-155 Stud-
ies looking at radioiodine as a treatment for nontoxic multinodular goi-
ter show volume reduction of one-third to two-thirds occurring in
more than 80% of patients, with 70% to 80% of patients having a
decrease in obstructive symptomatology. Higher likelihood of success
occurs with younger patients, smaller goiters, cervical (versus subster-
nal) goiters, and higher dose/uptake of radioiodine.121 Complications
include radiation thyroiditis with transient thyrotoxicosis and potential
acute worsening of airway symptoms in less than 5% of patients, the
need for greater than one dose of radioiodine in up to 20% of patients,
hypothyroidism in 60% of patients (increased risk if positive antithy-
roid peroxidase autoantibodies, family history of hypothyroidism, or
59.e2
in patients with small goiters), and radiation-induced Graves’ disease
in up to 10% of patients. The high doses of radioiodine used increase
the estimated lifetime risk of cancers outside the thyroid gland by 1.6%
overall and by 0.5% for patients older than age 65.111,137,138,156-163
Radioiodine in the treatment of a large goiter that is affecting the
airway deserves special attention. Le Moli found that the larger the goi-
ter, the less responsive it is to radioiodine.161 Nygaard found transient
increase in goiter size in approximately 7% of patients treated. In these
patients increased size averaged 25%, with a range from 11% to
60%.137,158,162 Bonnema also found that within 1 week of radioiodine
treatment, the tracheal cross-sectional area decreased by 9.2% from
an initial value, with 33% being the greatest reduction in tracheal caliber
seen.111 Radioiodine treatment should be considered only in patients
with smaller goiters without any impact on airway and in patients
who could not otherwise tolerate surgery.138 The use of radioiodine
is an ill-advised treatment in patients with substernal goiter who have
substantial airway compression.56 In our goiter series, we found that
one-third of surgical patients had failed medical management with
either T4 or radioactive iodine treatment. Failure of these medical treat-
ments did not increase surgical complication rates. However, we appre-
ciate that radioiodine treatment could potentially increase scarring and
vascularity at the level of the thyroid capsule, which may present a chal-
lenge in subsequent surgery.12
60 SECTION 2 Benign Thyroid Disease
BOX 6.5 Surgical Indications for
Multinodular Goiter
1. Clear-cut significant regional aerodigestive tract symptom without other
cause
2. Computed tomography (CT) with tracheal compression
3. Masses greater than 5 cm
4. Goiter with subclinical or frank hyperthyroidism
5. All patients with malignancy suspected or proved
6. All patients with substernal goiter
cosmetic concern or those greater than 5 cm, given the increased risk of
regional symptoms at or above this size and the decreased accuracy of
FNA for excluding malignancy; (4) goiter patients with subclinical
hyperthyroidism; (5) patients in whom carcinoma is suspected or
proven; and (6) all patients with substernal extension. In our practice,
in general, the presence of substernal goiter is a surgical indication
because of the strong association of tracheal compression and subster-
nal growth and because the mediastinal component is difficult to follow
on physical examination or with fine-needle biopsy (Box 6.5).12 In our
series, substernal extent was the surgical indication in the majority of
cases (78%), because this factor is sufficient to warrant excision at
our institutions. Additional surgical indications are as follows: com-
pressive symptoms (49.5%), concern for cancer (17%), patient’s
desire/cosmesis (3%), nonthyroid local neoplasm (1%), and other/non-
specified (1%).85
Goiter: Risk of Malignancy
Please see the Expert Consult website for more discussion of this topic.
Surgery for Substernal Goiter
Please see the Expert Consult website for more discussion of this topic.
INTUBATION OF THE GOITER PATIENT AND
LARYNGEAL EDEMA
Intubation generally proceeds well in patients with large cervical and sub-
sternal goiters, but it can occasionally be difficult. When difficult, anesthe-
sia induction and intubation can represent a dramatic and life-threatening
process, given the fact that emergent or “under local” tracheotomies gen-
erally are not options because of the mass of the overlying goiter. In
patients with goiter, there may be evidence of substantial laryngeal devi-
ation and perhaps vocal cord paralysis at intubation. The surgeon who
performs the preoperative laryngoscopy should convey all information
regarding the appearance of the larynx, presence of deviation, and vocal
cord paralysis to the anesthesia staff, and both the surgeon and the anes-
thesiologist should review the preoperative CT scans and examine the
patient together before induction. Cervical goiter with significant superior
pole expansion can indent the supraglottic hypopharynx and lead to
difficult laryngeal examination and difficult intubation.
The method of intubation and the size of the tube and contingency
plans can be discussed and decided upon through these discussions.
Typically, a straightforward induction with transoral intubation can
be performed. Laryngeal deviation generally does not represent a prob-
lem, and tracheal compression generally yields to a reasonably sized
endotracheal tube. An alternative and safe method that we favor is
an awake, sitting up, fiberoptic transnasal intubation. This is an espe-
cially reasonable course of action if there is any doubt as to the ade-
quacy of a sedated mask anesthesia airway, particularly if the larynx
is significantly deviated by the cervical component of the goiter. Video
laryngoscopes are also an excellent adjunct for intubation in such
patients. Maximum tracheal compression in cervical and substernal
goiter usually occurs at the thoracic inlet but may be present further
distally.33 As previously noted, tracheal compression by benign goiter
typically yields to a reasonably sized endotracheal tube. One exception
is when there is malignant infiltration of the trachea, especially if there
is intraluminal disease. In these circumstances, transoral broncho-
scopic intubation with bronchoscopic core-out can lead to satisfactory
airway. Once again, preoperative CT scanning empowers the surgeon.
Vigilance and recognition of nonthyroid factors, such as jaw and ton-
gue size, anteriorly positioned larynx, and available degree of head
extension, are also important determinants of difficult intubation.
Our experience has shown that a significant problem in patients
with large cervical or substernal goiters, especially with bilateral
circumferential goiters, is the development of laryngeal edema with ini-
tial intubation attempts by anesthesia. The larynx, which represents the
extreme distal end of the airway projected into the hypopharynx,
likely has chronically reduced venous and lymphatic drainage as a
result of a large, constricting bilateral goiter. Such a larynx is easily
made edematous with multiple unsuccessful intubation attempts. This
edema can last for weeks postoperatively, sometimes requiring trache-
otomy, which usually can be removed after edema resolves. It is
therefore best to intubate once correctly. Intubation problems,
although rare, can quickly spell disaster. The propensity for laryngeal
edema from intubation attempts with goiter has been emphasized in
the case reports of Hassard.172 In our series of 200 patients with goiter,
we encountered difficult intubation in only four cases (2%). There were
no significant predictors of difficult intubation, including size, subster-
nal extension, preoperative compressive symptoms, or radiographic
presence of tracheal deviation or compression. Tracheotomy was per-
formed in only 3% of patients and was done electively at the time of
thyroidectomy. Tracheotomy was performed either because of concern
about laryngeal edema from multiple intubation attempts or in cases
where neural monitoring was not used and the question of vocal cord
dysfunction was raised, especially if one vocal cord was known to be
paralyzed preoperatively. With neural monitoring, greater certainty
exists as to the functional status of both nerves during surgery (see
Chapter 36, Surgical Anatomy and Monitoring of the Recurrent Laryn-
geal Nerve).85
GOITER SURGERY
Extent of Surgery
Decisions regarding the extent of surgery relate to the balance between
operative complications and the risk of recurrence. Some suggest total
thyroidectomy for goiter,173-175 while others recommend a more con-
servative initial surgical plan,11 and some, such as Kraimps, support a
selectively aggressive surgical treatment plan based on extent of
disease.176 A 2015 Cochrane database systematic review on total or
near-total thyroidectomy versus subtotal thyroidectomy showed
decreased recurrence rates with total thyroidectomy (although evidence
was limited) and recommended additional long-term randomized con-
trolled trials (RCTs) to address questions of reoperation rates, adverse
events, and thyroid cancer incidence rates.177 Complication rates must
be kept extremely low in the setting of treatment of benign thyroid dis-
ease. Therefore we suggest a conservative philosophy, tailoring the
extent of surgery to the initial disease with the minimum procedure
being a total unilateral lobar resection, reserving bilateral surgery for
significant bilateral goiter. In our series, this surgical philosophy
resulted in unilateral surgery in 63% of patients and bilateral surgery
in 37%. Patients undergoing initial surgery at our center experienced
a 1.5% recurrence rate.85
60.e1
Goiter: Risk of Malignancy
Patients with goiter in whom carcinoma is suspected or proven should
undergo surgical excision. The typical pathology report for substernal
or surgical goiter reveals adenomatous nodules with old hemorrhage,
calcification, cyst formation, fibrosis, and sometimes, focal thyroiditis.
The pathology report may also be primarily thyroiditis in some circum-
stances. The rate of malignancy varies in cervical and substernal goiter
surgical specimens. Singh, Lucente, and Shaha, in reviewing the surgical
literature, noted an average rate of 8.3%, with a range of 0% to 40%.89
Katlic, Grillo, and Wang, in 80 substernal goiters, noted only a 2% rate,
whereas Sanders et al. noted a rate as high as 21%.11,20
There have been some studies looking at the risk of malignancy
between cervical and retrosternal goiter. White et al. showed no
increase in the incidence of malignancy when retrosternal and cervical
goiter were compared.165 In another study of 390 retrosternal goiter
cases, cancer incidence was not increased in retrosternal versus cervical
goiters. However, most cancer foci in retrosternal goiter were intratho-
racic and not identified on preoperative ultrasound.165,166 In contrast,
Campbell et al. studied 538 patients, 394 with substernal goiter and 144
with cervical goiter, and showed an incidence of malignancy in 13.7% of
substernal goiters versus 6.3% of cervical goiters (p ¼ 0.003).167
Certainly some, though not all, of these malignancies are occult and
incidentally noted. Unfortunately, a long and stable history does not
preclude malignancy. The alternative to surgical extirpation of multiple
thyroid nodules is multiple FNAs of all nodules meeting indications for
biopsy.135 Given that negative FNAs of all sizable nodules do not rule
out malignancy, we believe it is reasonable to abstain from aspirating all
nodules in a patient who is scheduled for goiter surgery and who is not
suspected to harbor malignancy based on physical examination and CT
scanning, especially when total thyroidectomy is planned.

Surgery for Substernal Goiter
We believe that all patients, whether symptomatic or not, with subster-
nal goiter should be considered for surgery. Substernal extension in our
series of more than 200 large cervical and substernal goiters highly cor-
relates with airway compression. This is not surprising, considering the
bony confines of the thoracic inlet.12 The thoracic component of a sub-
sternal goiter is also unavailable for ongoing clinical examination or
FNA. If the substernal component acutely enlarges, the airway is
affected on a mediastinal level. Most substernal goiter series note a
small but significant rate of acute airway emergency. Neither
60.e2
tracheotomy nor intubation may relieve an obstruction associated with
mediastinal airway compression.11 Aside from typical regional symp-
toms, benign substernal goiter has also been associated with SVC syn-
drome, downhill esophageal varices, RLN paralysis, phrenic paralysis,
Horner’s syndrome, chylothorax, abscess formation, and cerebral vas-
cular accident.76,95,168-171 Given the propensity for regional symptom-
atology, the lack of other reasonable treatment options, and the low
complication rate of surgery, all patients with substernal goiter should
be considered for surgery, assuming their medical condition permits.
 CHAPTER 6 Surgery of Cervical and Substernal Goiter
BOX 6.6 Extent of Surgery for Goiter:
Summary
• We believe that complication rates must be low in the setting of surgery for
benign thyroid disease.
• Less than unilateral lobectomy leads to extremely high recurrence rates and
difficult reoperations and is to be condemned.
• The extent of surgery should be rationally tailored to the extent of initial
disease. Dominant goitrous enlargement should be treated with total lobec-
tomy on that side. Preoperative assessment with imaging will help docu-
ment the extent of surgery necessary on the contralateral side.
• With clear-cut unilateral disease, total lobectomy is appropriate.
• With clear-cut evidence of bilateral goiter, bilateral surgery is appropriate.
• Consideration should be given for more aggressive surgery in young females
and in patients with a positive family history of thyroid disease who may
have a higher recurrence rate.
• In patients who have required multiple thyroid surgeries for benign recur-
rence and still have some remnant tissue remaining after the last revision
surgery, radioactive iodine ablation can be considered.
Please see the Expert Consult website for more discussion of
this topic.
Our experience, similar to the work of Berghout et al., has suggested
a greater likelihood of recurrence in females and in patients with a pos-
itive family history of thyroid disease.85,184 Overall, females were found
to be three times more likely to require revision surgery, and those with
a positive family history of thyroid disease were six times more likely to
require revision surgery.85 Others have found no such increased risk in
these populations.176 We now tend to be more aggressive in females
and in those with a positive family history, especially if they are young.
Furthermore, we have treated many patients with recurrent disease and
appreciate the difficulty of these cases and of the occasional need to
leave at least a small thyroid tissue remnant in such revision cases.
However, contrary to most reports in the literature, revision cases in
our series of patients with goiter, whether unilateral or bilateral, second,
third, or fourth revisions, were not more likely to be associated with
postoperative complications.85 We have used radioactive iodine post-
operatively after complex multiple revision cases to avoid the need
for additional reoperation in these circumstances (Box 6.6).
Hashimoto’s Thyroiditis
Please see the Expert Consult website for more discussion of this topic.
SURGICAL TECHNIQUE FOR GOITER
Patient positioning is important. We prefer a thyroid inflatable bag
under the shoulders. The surgeon and anesthesiology staff must be
comfortable with the degree of head support. The patient is placed into
a semisitting position to reduce venous pressure.
Incision
A generous collar incision is mandatory. Endoscopic or minimal access
approaches are not appropriate here. When unilateral glandular
enlargement has resulted in significant deformity of the anterior neck,
that side of the incision can be curved slightly higher because after
resection the skin will come to fall caudally to some extent. The incision
for a large bilateral cervical goiter extends to the lateral edge of the ster-
nocleidomastoid (SCM) muscle to allow for exposure of the bilateral
carotid sheath contents. A subplatysmal upper flap is developed.
61
A lower flap is typically not necessary. Flaps can be sutured in place
or several Gelpi retractors, or Beckman goiter retractors, can be used.
Strap Muscles
It has frequently been recommended to routinely section the strap mus-
cles during goiter surgery. Certainly, if there is any question that strap
division would help exposure, it should be done without hesitation. This
is most often necessary in revision surgery where strap muscle division
had been performed during the initial surgery. The muscles in this
circumstance are significantly scarred to the surface of the goiter. In
first-time surgery in which superior pole exposure is limited, we recom-
mend a “mini strap section” by an isolated incision of the cranial head of
the sternothyroid muscle. Although subtle and transient voice changes
may arguably accompany strap division, they are of little consequence
overall compared with potential division of the RLN or external branch
of the superior laryngeal nerve (SLN) through poor exposure. In some
massive cervical goiters, the SCM muscle can be sectioned as well as
the strap muscles, although this is uncommon. It, like the strap muscles,
can be sutured at the completion of surgery with little ill effect. If the strap
muscles are sectioned, it is important during surgery to either suture or
place a clamp on the divided edges, which have a tendency to retract, with
a resultant loss of the perithyroidal plane they define. If the strap muscles
are completely sectioned, it is best first to define their lateral edge, which
can blend with tissue adjacent to the jugular vein and other carotid
sheath contents. In most of the goiter surgeries that we have performed,
strap muscles are preserved and retracted. This preserves a perithyroidal
plane better than sectioning the muscles in some circumstances, and it
helps to preserve anatomic organization to the neck base that can be
substantially altered by goitrous change.
Importance of Carotid Sheath
The carotid sheath (including the carotid artery, jugular vein, and vagus
nerve) is to the initial steps in goiter surgery what the lateral thyroid
region (with RLN and inferior thyroid artery) is to surgery of a
normal-sized thyroid gland (Figure 6.3). It is extremely helpful to
dissect the carotid artery, jugular vein, and identify the vagus nerve
early on during the case. A lateral or inferior approach to the nerve
may be used initially, with a superior approach reserved for use only
when the goiter size and position prevent the more standard technique
(Figure 6.4). A large cervical goiter frequently extends to the carotid
sheath, necessitating this dissection, which allows reflection of the jug-
ular vein, and sometimes the carotid artery and vagus, off the lateral
surface of the goiter. Identification of the vagus nerve allows intermit-
tent vagal stimulation, a very helpful technique during substernal goiter
surgery (see the discussion of vagal monitoring during goiter surgery
later in this chapter). The identification and dissection of the carotid
artery, as it extends in the neck and more importantly as it extends into
the mediastinum, are essential for the surgeon to understand the sub-
sternal goiter’s relationship to the mediastinum and aortic arch (see
Figure 6.3). Once the strap muscles and carotid sheath are dealt with,
the procedure continues with the steps typical of routine thyroidec-
tomy, including middle thyroid vein division, inferior thyroid vein
division, and identification of the inferior thyroid artery. Because of
the size of the goiter, the inferior thyroid artery may not be able to
be identified during this segment of the surgery but can be identified
later after goiter delivery. The branches of the inferior thyroid artery
are taken directly on the thyroid capsule to preserve parathyroid tissue
and vascularization.
Goiter and Recurrent Laryngeal Nerve
Approaches to the RLN can be made laterally, inferiorly, or superiorly
(see Chapter 36, Surgical Anatomy and Monitoring of the Recurrent
61.e1
Studies looking at the extent of surgery and benign multinodular goiter
recurrence are confounded by several factors: (1) variability in the ini-
tial extent of thyroid gland nodularity, (2) variability in the extent of
recognition of contralateral nodularity at first surgery, (3) insufficient
follow-up periods in many studies, and (4) variable definitions of recur-
rence. Some studies, for example, diagnose recurrence based on an
asymptomatic, ultrasonographic identification of thyroid nodularity.
A more reasonable definition of recurrence is the development of clin-
ical, palpable thyroid enlargement, which again meets surgical criteria
for goiter treatment. The question is, can less than total thyroidectomy
and even hemithyroidectomy be performed if anodular normal tissue is
left? Complication rates of bilateral surgery are expected to be higher
than unilateral surgery. Conservative initial surgery also allows a
patient to avoid a lifetime of replacement therapy. However, long-term
studies show the overall recurrence rate after surgery for goiter is in the
range of 15% to 42%.10,178,179 When recurrence occurs and requires
revision goiter surgery, the complication rates are significantly higher
than for first-time surgery, with RLN rates of paralysis ranging from 3%
to 18% and permanent hypoparathyroidism ranging from 0% to 25%
(see Chapter 9, Reoperation for Benign Thyroid Disease).180-183
The literature offers conflicting conclusions on factors associated
with recurrence of goiter. The duration of postoperative follow-up is
important to consider when examining recurrence of goiter. The data
offered by Delbridge, Guinea, and Reeve suggest recurrences may
require 10 to 13 years to manifest.173 Rojdmark and Jarhult found that
the overall recurrence rate rose to 42% with 30-year postoperative
follow-up.179 Bistrup et al., in a randomized, prospective, nonplacebo,
controlled study, showed rates of recurrence for nontoxic goiter
between 14% and 22%. They found the extent of surgery did not relate
to the likelihood of recurrence.178 Hegedus, Nygaard, and Hansen
found that the weight of thyroid tissue resected was actually greater
in those patients who developed subsequent recurrence.10 However,
Berghout et al., with a 7-year follow-up, found that unilateral surgery
was associated with higher recurrence rates than bilateral surgery.184
Australian workers have shown that in patients with unilateral disease,
hemithyroidectomy results in a 12% recurrence rate in the contralateral
lobe.185
Other workers have supported a philosophy of total thyroidectomy
or bilateral subtotal thyroidectomy in most patients with goiter.173,174
Subtotal thyroidectomy is defined as total lobectomy with a contralat-
eral remnant approximately equivalent to a small normal lobe, whereas
in near total thyroidectomy, a remnant of several grams is maintained
in the contralateral bed typically adjacent to the RLN entry point. In
patients who require bilateral surgery, the technique of subtotal lobec-
tomy has been both recommended and condemned.25,182,186,187 Cohen-
Kerem, in a study of 124 patients with a follow-up of 7.6 years, noted
that with bilateral subtotal technique, only 4% of patients required
additional surgery.186 Pappalardo found similar rates of recurrence
in 69 patients treated for benign goiter randomized to total versus sub-
total procedures.183 Reeve et al., however, found subtotal thyroidec-
tomy was associated with a 23% recurrence rate.187 Barczy
nski et al.,
in a randomized trial of total versus bilateral subtotal thyroidectomy
versus the Dunhill procedure (total lobectomy with contralateral partial
or subtotal lobectomy), showed decreased recurrence rates with total
thyroidectomy and no increase in the rate of permanent morbidity
in 600 patients at 10-year follow-up.175 Clearly, less than a lobectomy
as a minimum procedure is unwise. Cohen-Kerem et al. found a recur-
rence rate after unilateral subtotal resection was 60%.186 Kocher noted
an 18% recurrence rate with nodule enucleation.188 Kraimps, using a
selectively aggressive surgical treatment plan based on the extent of dis-
ease, noted very low recurrence rates of 1% with lobectomy and 3% with
bilateral surgery.176 Others have supported such a selectively aggressive
approach to surgery based on extent of disease.6,88,189
Modern series show that in skilled hands, total thyroidectomy for
goiter can be performed without significant complications, given the
work of Reeve et al., Netterville et al., and others.173,187,190 Delbridge,
Guinea, and Reeve noted that for patients with bilateral multinodular
goiter, total thyroidectomy can be associated with permanent paralysis
of the RLN in 0.5% and permanent hypoparathyroidism in 0.4%.173
They believe the policy of autotransplantation of at least one parathy-
roid during each total thyroidectomy is in part responsible for the low
rate of hypoparathyroidism.173 Grant, in his commentary of this article,
wrote, “to consider total thyroidectomy as the only acceptable alterna-
tive would probably risk causing more cases of troublesome hypopara-
thyroidism than it would prevent cases of goiter recurrence.…
Moreover, it seems difficult to assert total thyroidectomy as the only
option for benign disease when many surgical authorities strongly dis-
agree with its use, even in thyroid cancer.”173 Some workers have sug-
gested that the likelihood of identifying cancer in goiter specimens
justifies total thyroidectomy. Most studies document an incidence of
malignancy in such specimens of between 3% and 17%. Most are small,
occult, incidentally noted malignancies within otherwise benign multi-
nodular goiters and would not normally justify an aggressive surgical
approach.11,20,191

Hashimoto’s Thyroiditis
Other variables important during surgery are the degree of capsular
blood vessel engorgement and friability, and goiter consistency. Goiters
that are soft and compressible are more easily manipulated during sur-
gery, whereas those that are firm can be challenging even when small.
Generally, glands affected by Hashimoto’s thyroiditis are more difficult
to work on than the more typical benign adenomatous goiter. Hashi-
moto’s glands, especially those resulting from the fibrotic variant of
61.e2
Hashimoto’s thyroiditis, can be firm and less compressible and have
a friable, “sticky” surface, which bleeds easily. Such goiters can be asso-
ciated with multiple perithyroidal lymph nodes that can sometimes
make a surgeon consider papillary carcinoma. Such nodes also make
parathyroid identification more challenging. The rare fibrous variant
of Hashimoto’s thyroiditis is an especially firm variant, which makes
the performance of less than total lobectomy challenging.
62 SECTION 2 Benign Thyroid Disease

Tracheal cartilage

Esophagus
Right lobe of
thyroid gland Left recurrent
laryngeal nerve

Right vagus nerve Left common

(CN X) carotid artery

Left vagus nerve

(CN X)
Right recurrent
laryngeal nerve

Arch of aorta

Fig. 6.3 Neural and vascular anatomy of the neck base. (From Janfaza P, et al, eds. Surgical Anatomy of the
Head and Neck. Philadelphia: Lippincott Williams & Wilkins; 2001. With permission.)

Laryngeal Nerve). Goiter may significantly distort the position of the
RLN. In our experience with large cervical and substernal goiters, we
have found that in nearly 16% of cases the RLN was entrapped on
the surface through fascial band fixation or splayed over the surface
of the goiter in such a way that significant traction or goiter delivery
without RLN identification would have definitively injured (stretched
or avulsed) the nerve (Figure 6.5).85 We found that left and right lobes
were equally affected. Cases of fixation and nerve splaying were more
likely with increased goiter size, substernal extension, significant tra-
cheal compression, and intubation difficulties. In our unpublished
series of 184 cases of thyroidectomy not involving goiter, we found
no such cases of fixation or splaying other than in cases of malignant
infiltration. It is interesting to note that Sinclair’s work demonstrates
that postoperative RLN paralysis in patients with substernal goiter in
whom the RLN was not specifically identified during blind digital goiter
delivery was 17.5%. Sinclair wrote in several cases that the nerve was
associated with the thyroid gland and
was at serious risk when the retrosternal mass was mobilized into
the neck [during] a maneuver usually achieved by dislocating the
mass with a finger from below and behind. I believe that this haz-
ard must be recognized by all thyroid surgeons and that every
strand of tissue stretched over the retrosternal component of the
goiter should be presumed to be nerve until anatomically proved
otherwise.192
Sinclair’s rate of paralysis and our rate of nerves at risk are similar.
 CHAPTER 6 Surgery of Cervical and Substernal Goiter
We believe that, because of the possibility of nerve fixation and
splaying on the undersurface of the goiter, blunt dissection without
nerve identification risks stretch injury. Identification of the RLN in
such cases is a necessary initial step. The nerve that is fixed to or splayed
on the undersurface of the goiter should be dissected before delivery of
the gland. The nerve can be identified through a superior approach and
can be dissected retrograde off the goiter before digital delivery of
the goiter (see Figure 6.4). This dissection is coupled with dissection
of the vagus nerve in the carotid sheath laterally and allows the pathway
of the vagus and RLNs to be predicted in the mediastinum. After goiter
resection the RLN so dissected can appear significantly redundant but
will stimulate normally and function postoperatively, despite the
RLN
Ligament
of Berry
Reflected
superior
thyroid pole
Fig. 6.4 Superior approach to the recurrent laryngeal nerve (RLN).
Larynx and
trachea
RLN fixed and
splayed on
undersurface
of goiter
Fig. 6.5 Demonstration of fixation and splaying of the RLN in patients with substernal goiter. RLN, recurrent
laryngeal nerve.
63
intraoperative appearance of laxity (see Figure 6.6, available on
expertconsult.com). In some circumstances if the goiter is soft and
compressible, the inferior pole can be retracted cranially without deliv-
ering it out of the neck, and the RLN, despite impressive goiter size, can
be identified through a normal inferior approach.
The Special Case of Retrotracheal Cervical and Posterior
Mediastinal Goiter: The Ventral Recurrent
Laryngeal Nerve
Retrotracheal cervical goiter and posterior mediastinal goiters (subster-
nal goiter type IIA, B) represent especially unique surgical challenges
(Figure 6.7). Approximately 9% to 15% of all substernal goiters extend
into the posterior mediastinum.11,22,29,30,86 The chief difficulty is that in
these cases, thyroid tissue has excavated posteriorly and deeply to the
RLN. This causes displacement of the RLN ventral to the thyroid lobar
tissue, defined as an L2b (left) or R2b (right) RLN, according to the
International RLN Anatomic Classification System.193 As the posterior
mediastinal goiter descends, it pushes the trachea anteriorly and splays
the great vessels.26,27,194 For the surgeon the ventral RLN is a disorient-
ing and high-risk RLN position. The RLN in all other cases of thyroid-
ectomy is always deep to the thyroid gland. The most complex posterior
mediastinal goiters are those that descend from the left lobe and then
cross, being pushed by the aortic arch and its branches to the right tho-
rax (substernal goiter type IIB). These crossings may occur either
behind both the trachea and esophagus (type IIB1) or between the
trachea and esophagus (type IIB2; see Table 6.1 and Figure 6.1,
A-H).26,27,30 Some have recommended sternotomy,30,194 and some
advocate posterolateral right thoracotomy22,195,196 along with a cervical
approach. Right thoracotomy, when necessary, is performed through
the right fourth and fifth intercostal space. The lung is retracted, and
the goiter is identified posterior to the SVC, superior to the azygous
vein, and anterior to the vertebral column. The pleura over the goiter
is incised, and the goiter is manipulated into the thoracic inlet with the
help of traction from above.60 Katlic, Grillo, and Wang found 7 of 80
patients with substernal goiter extended into the posterior mediasti-
num that could typically be removed through a cervical approach.11
DeAndrade’s extensive experience with posterior mediastinal goiter
Cervical
component
Substernal
component
Clavicle
63.e1

Fig. 6.6 A and B, Patient 1. This computed tomography (CT) scan was obtained after the patient had two pre-
vious thyroidectomies, 10 and 20 years before presentation. This surgery represented her third revision thyroid-
ectomy. Preoperative diagnosis at an outside institution was asthma. The mass was benign. The recurrent
laryngeal nerves were identified and monitored. There was normal cord motion postoperatively. The trachea
was compressed, but there was no evidence of tracheomalacia, and the patient did not require tracheotomy.
Airway symptoms resolved postoperatively. C–E, Patient 2. Elderly woman with a large, multilobulated, calcified
cervical goiter. The recurrent laryngeal nerve was entrapped within layers of fascia adjacent to the lateral aspect
of the left thyroid lobe (see the white band on the side of the goiter in E). Neural monitoring allowed identification
and preservation of both recurrent laryngeal nerves, with normal cord function postoperatively.
(Continued)
 63.e2

Fig. 6.6, cont’d F and G, Patient 3. Large cervical goiter. Note the redistribution of subcutaneous veins sec-
ondary to jugular compression. The asymmetry of the goiter resulted in larynx rotation, with the left recurrent
laryngeal nerve entering the rotated larynx in the midline. The recurrent laryngeal nerves were identified and
preserved, with normal cord function postoperatively. H–J, Patient 4. Patient with a large cervical and substernal
goiter. The mass was resected transcervically without sternal split, with normal cord function postoperatively.
K–O, Patient 5. Large cervical and substernal goiter extending to the aortic arch, resected transcervically without
sternal split, with normal cord function postoperatively. The patient had undergone parathyroid exploration
17 years previously.
(Continued)
63.e3

Fig. 6.6, cont’d P–T, Patient 6. Elderly woman with large cervical and bilateral substernal goiter. The right sub-
sternal mass extended retrotracheally. The bilateral goiter was resected, with total thyroidectomy transcervically
without sternal split and with normal cord function postoperatively.
(Continued)
 63.e4

Fig. 6.6, cont’d U–Z, Patient 7. Elderly woman with cervical goiter with significant left substernal extension to
below the aortic arch down to the azygous vein. The mass was excised transcervically without sternal split and
without change to preoperative vocal cord function.
(Continued)
63.e5

Fig. 6.6, cont’d (E, H–J, P–T, Reprinted with modification, with permission from Montgomery W, ed. Surgery
of the Larynx, Trachea, Esophagus, and Neck. Philadelphia: WB Saunders; 2002.)
64 SECTION 2 Benign Thyroid Disease

Fig. 6.7 Retrotracheal masses excavate the region posterior to the trachea, bringing the nerve ventral to the
lesion. A, A cervical goiter with some retrotracheal extent. B, At surgery, the recurrent laryngeal nerve (RLN)
was found to be displaced anteriorly and was adherent to the ventral surface of the mass. The nerve was iden-
tified through neural monitoring, dissected away, and functioned normally postoperatively. C, Female with large
retrotracheal mass shown on computed tomography (CT). D, The RLN was ventral to this mass seen here on
magnetic resonance imaging (MRI) and was identified with neural monitoring, dissected away, and functioned
normally postoperatively. E and F, Lymphangioma arising from the inferior pole of the thyroid, extending infe-
riorly into the mediastinum approximately 13 cm. E and F, Axial cuts in the neck base and upper chest. The mass
was excised completely and was deep to the RLN, which was closely associated with it. The nerve was iden-
tified through neural monitoring, dissected away, and functioned normally postoperatively. The lymphangioma
was resected completely.
 CHAPTER 6 Surgery of Cervical and Substernal Goiter 65

Fig. 6.7, cont’d G, Asymmetric goiter that caused rotation of the larynx. The RLN entry point was rotated
because of the laryngeal rotation such that the nerve entered the larynx in the midline. H, Cervical goiter that
had a tightly adherent RLN through crossing vessels on the undersurface of the left smaller side. This RLN was
dissected away and preserved. Such vessels can be seen and predicted on preoperative CT as shown here.

found that virtually all could be extracted through a cervical incision
and were vascularized by the inferior thyroid artery.29 Certainly, these
cases make clear the need for preoperative imaging and should be han-
dled by experienced surgical teams (see Chapter 7, Approach to the
Mediastinum: Transcervical, Transsternal, and Video-Assisted).
Superior Goiter Extent
Please see the Expert Consult website for more discussion of this topic,
including Figure 6.8.
Parathyroid Preservation During Goiter Surgery
The distal inferior thyroid artery is taken after the RLN is identified and
either before or after goiter delivery. The artery is taken directly on the
thyroid capsule to reduce the risk of parathyroid ischemia. The superior
parathyroid glands are more constant in position and are more fre-
quently seen at thyroidectomy for goiter; therefore they are more read-
ily preserved. In their series of 80 substernal goiters, Katlic, Grillo, and
Wang noted that upper glands were seen twice as often as lower
glands.11 The inferior parathyroid gland is more widely distributed
and more likely to be significantly displaced by inferior pole goitrous
change. Therefore our real emphasis during goiter surgery should be
on superior parathyroid preservation. Inferiorly, we must strictly
adhere to capsular dissection so as to preserve displaced inferior para-
thyroid glands. It is important to emphasize that with goiter surgery, as
with all thyroid surgery, any resected thyroid specimen must be metic-
ulously examined for capsular parathyroid glands before being sent to
pathology. Any capsular parathyroid glands that are found should be
dissected off, biopsied to confirm parathyroid tissue, and then auto-
transplanted. These glands may be found within folds and crevices
of the goiter surface.
Substernal Goiter Techniques for Delivery
As previously described, after the RLN is identified and completely dis-
sected away from the goiter (typically allowing it to fall away postero-
laterally), finger dissection in a strictly capsular plane, with an
understanding of the specific goiter/mediastinal anatomy, can allow
for safe goiter delivery (Figures 6.9 and 6.10)—one finger on a strictly
capsular location medially adjacent to the trachea and one finger later-
ally adjacent to the carotid sheath. The goiter is slowly incrementally
mobilized upward. Thin, fascial band attachments drawn up with the
finger are stimulated with the nerve stimulator and cauterized or
clamped. Slow, step-by-step incremental goiter delivery is achieved
from the mediastinum with substernal goiter or out of the thyroid
bed for cervical goiter. RLN identification and dissection before deliv-
ery are mandatory, as previously noted. The vagus may be intermit-
tently stimulated as the goiter is mobilized, or continuous vagal
monitoring can be used (see Chapter 36, Surgical Anatomy and Mon-
itoring of the Recurrent Laryngeal Nerve). In patients with large sub-
sternal goiters with a contralateral cervical component, performing
surgery on the contralateral side first may be necessary to increase
the mobility of the laryngotracheal complex and to allow for substernal
goiter delivery. If all these maneuvers are not effective, sternotomy may
be considered. Despite nearly 80% of patients having substernal exten-
sion, the sternotomy rate was only 1% in our series of patients with
goiter,85 which is consistent with that seen in the literature.197-199 It is
important that any surgeon who does not routinely perform sternotomy
himself or herself review preoperative CT scans of patients with subster-
nal goiters with thoracic surgical colleagues and arrange the surgical date
when a thoracic surgeon is available, if needed.
Substernal goiter is a product of the neck. The blood supply to sub-
sternal goiters is almost always cervical (i.e., the inferior thyroid artery).
One must keep in mind that although cervical goiters’ and the majority
of substernal goiters’ blood supplies are through the inferior thyroid
artery, there are rare cases of substernal and even cervical goiter with
aberrant intrathoracic blood supply.22,82 Substernal goiters thus infre-
quently obtain significant blood supply from mediastinal vessels such
as the thyroid ima, subclavian, or internal mammary artery or
aorta.25,34,36,86 In our series of 200 thyroidectomies for goiter, we found
only two cases where the blood supply to the thyroid mass was provided
by vessels of intrathoracic origin.85 With this in mind it is best that fas-
cial bands produced during digital dissection of the substernal goiter be
cauterized only if transparent. Thicker pedicles of tissue should be
clamped and securely tied only after the RLN and vagus locations
are completely understood along their full course.
Morselization is a technique that has been performed in the past to
help reduce goiter size and provide for delivery. It was first described by
Kocher in 1889, popularized by Lahey in 1945, and has its more recent
proponents.20,78,188,200 We believe that this technique should be aban-
doned because it risks significant and perhaps uncontrollable hemor-
rhage as well as the spread of carcinoma if ultimately found to be
 65.e1

Superior Goiter Extent
The superior extent of the goiter is more easily handled with good expo-
sure of the superior pole region. As previously noted, the superior pole
region can be more widely exposed through an isolated section of the
head of the sternothyroid muscle along with an adequately raised supe-
rior skin flap. Right-angle clamps are very helpful in superior pole dis-
section. Large superior-pole vessels should be doubly tied, because they
can lead to troublesome bleeding and retract if not controlled appropri-
ately. We have seen several goiters with significant superior pole devel-
opment extending to the retropharyngeal region and tonsillar fossa
(Figure 6.8, A and B). Care should be taken to identify and avoid injury
to the external branch of the SLN, which is at greater risk of injury in
these cases (see Chapter 35, Surgical Anatomy and Monitoring of the
Superior Laryngeal Nerve).

Fig. 6.8 A and B, Cervical goiter can extend superiorly to the retropharyngeal region.
66 SECTION 2 Benign Thyroid Disease

Right recurrent
laryngeal nerve
Left recurrent Thoracic
laryngeal nerve duct
Right jugular Left jugular
trunk trunk

Right Left
supraclavicular supraclavicular
trunk trunk
Right
lymphatic duct
Anterior
mediastinal
trunk Inferior
Posterior thyroid
intercostal vein
trunk
Internal
thoracic
trunk
Right Left
subclavian subclavian
trunk trunk

Superior vena cava

Left internal
thoracic trunk
Internal thoracic
trunk
CN X
Azygous vein

Posterior
mediastinal trunk

Fig. 6.9 Vascular anatomy of the neck base and upper mediastinum. (From Janfaza P, et al, eds. Surgical Anat-
omy of the Head and Neck. Philadelphia: Lippincott Williams & Wilkins; 2001. With permission.)

present.11 Johnson and Swente have reported a case of mediastinal

hematoma and death after morselization of a large posterior mediasti-
nal goiter.22 Allo and Thompson described a form of morselization
with thyroid capsular incision and insertion of a suction.56 Recently,
a powered endoscopic debrider instrument initially designed for carti-
lage ablation during endoscopic knee surgery and later modified for
endoscopic sinus surgery was used for goiter morselization. This new
technology makes morselization no more appealing, given the risks
of bleeding and cancer dissemination.201 Cysts within the thyroid, if
benign, can be decompressed with a needle, although such a technique
is rarely necessary. A variety of instruments have been used to facilitate
substernal goiter delivery. Kocher introduced a mediastinal goiter
spoon to facilitate substernal goiter delivery. The use of this blunt
instrument breaks negative intrathoracic pressure and occupies less
space than the surgeon’s finger.188,202 Sanders has used a Foley catheter
placed into the mediastinum and inflated it to assist in the delivery of
substernal goiter without sternum split.20

Sternotomy for Substernal Goiter

Multiple substernal goiter series show sternotomy rates of between 1%
and 8% (see Chapter 7, Approach to the Mediastinum: Transcervical,
Fig. 6.10 Substernal goiter extension on the right, with tracheal deviation Transsternal, and Video-Assisted).11,20,56,58,86,90,91,101,203,204 Resection
in the upper mediastinum. of the medial one-third of the clavicle can also be used to increase
 CHAPTER 6 Surgery of Cervical and Substernal Goiter
the bony confines of the thoracic inlet (see Figure 6.10).205 Sternotomy
must, in all cases, be discussed preoperatively with the patient and
thoracic surgical colleagues. Clearly, there is increased morbidity asso-
ciated with the addition of a transthoracic approach. In a National
Surgical Quality Improvement Program (NSQIP) database review of
2716 patients with substernal goiter, Khan et al. showed increased rates
of unplanned intubation, need for transfusion, and length of hospital
stay.206 The decision to perform sternotomy should be considered
carefully and may be needed in the following circumstances:
• Known or suspected malignancy extending into the mediastinum
• Posterior mediastinal goiter if associated with contralateral exten-
sion (substernal goiter type IIB)
• Cases in which goiter blood supply is mediastinal. This information
may not always be available preoperatively. Patients with isolated
mediastinal goiter (substernal goiter type III) are at higher risk
for having noncervical blood supply.
• Cases associated with true SVC syndrome identified preoperatively,
which suggests substantial neck base/mediastinal venous obstruc-
tion. True SVC syndrome should raise the specter of mediastinal
malignancy rather than benign substernal goiter.
• Recurrent large substernal goiters
• Any case in which delivery maneuvers reveal an immobile subster-
nal component or where goitrous adhesions to surrounding medi-
astinal vessels and pleura are identified. Increased fibrosis or
scarring may be seen with prior radiation or surgery of the neck
or chest.
• Cases in which substernal goiter delivery is associated with substan-
tial mediastinal hemorrhage
• Cases in which the diameter of the intrathoracic component of the
goiter is substantially greater than the diameter of the thoracic inlet
• Cases where there is a long thin stalk from the cervical to the subster-
nal component. Such stalks may fragment with significant retraction,
especially if the mediastinal component is wide and bulbous.
Sternotomy or thoracotomy, as an isolated approach to substernal
goiter, is not appropriate because of the greater risk to the RLN during
such a procedure and the inability to effectively control the inferior thy-
roid artery.91,96
Ch 1 Pk: 627 µV
Ch 2 Pk: 509 µV
400 µV
AW vagal
Fig. 6.11 Electromyographic activity recorded in the thyroarytenoid/vocalis muscle of the larynx during ipsilat-
eral vagal nerve stimulation at 2 mA. Note the increased latency of the evoked response from stimulation artifact
compared with recurrent laryngeal nerve stimulation (stimulation artifact represented by the dotted line on
the left).
67
Vagal Monitoring During Goiter Surgery
We have used intermittent vagal stimulation to help preserve the vagus
and RLNs during surgery of large cervical and substernal goiters. Ini-
tially, the vagus nerve can be identified during carotid sheath dissection.
Vagal stimulation can be used intermittently during goiter surgery to
test the entire “circuit” (i.e., the entire ipsilateral vagus and RLN)
and ensure that it is intact during maneuvers that, because of goiter size
or substernal extent, risk neural stretch. Such maneuvers are performed
slowly with progressive incremental goiter delivery during ongoing
passive neural vagal monitoring and intermittent vagal stimulation.
If any change in stimulation is detected, the vagal and RLN course
and surgical maneuver are reevaluated to ensure that neural stretch
is not occurring.
We have seen no adverse neural, cardiopulmonary, neurologic, or
cardiovascular effects with stimulation of either the left or right vagus
despite repetitive, constant current pulse stimulation in the 1 to 2 mA
range, 4 pulses per second, 100 μs stimulation duration. The latency is
longer (average 6 to 8 ms), as one would expect, compared with RLN
stimulation during thyroidectomy (see Chapter 36, Surgical Anatomy
and Monitoring of the Recurrent Laryngeal Nerve; Figure 6.11). The
safety of vagal stimulation is in agreement with the works of Friedman
et al., Leonetti et al., and Eisele.207-209 Satoh, using penetrating elec-
trodes, transcutaneously stimulated the human vagus nerve in the
lower neck and found that ipsilateral thyroarytenoid electromyo-
graphic (EMG) activity was biphasic or triphasic, with latency of 6
to 8 ms (2 to 3 ms shorter on the right), amplitude of 0.4 to 0.7 mV,
and response duration of 4 to 5 ms.210 Friedman et al. documented
the cardiac safety of vagal stimulation in dogs with stimulation in
the 1 to 10 mA range, with 0.4 ms duration at 10 to 100 Hz.207 Inter-
mittent vagal stimulation through an implanted vagal coil electrode was
introduced in 1990 as treatment for some forms of refractive epilepsy.
Such stimulation has been shown to be well tolerated and safe.211,212
Lundy studied the laryngeal effects of vagal stimulation for epilepsy
in humans. The induced position of the vocal cord is felt to
depend on the amplitude and frequency of electrical stimulation (see
Chapter 36, Surgical Anatomy and Monitoring of the Recurrent Laryn-
geal Nerve). No adverse cardiopulmonary effects were seen with a
60 mS
500PP µV
0.00
mA
2.00
mA
68 SECTION 2 Benign Thyroid Disease
frequency of stimulation less than 40 Hz. At 3 mA, stimulation of less
than 10 Hz resulted in oscillation of the vocal cord at the rate of stim-
ulation. Stimulation from 10 to 30 Hz resulted in vocal cord abduction.
Stimulation at 40 Hz or greater resulted in adduction, with progression
to tetany. Others have documented vagal stimulation safety in
humans.203,213-215
Vagal stimulation can also be used to diagnose cases of nonrecur-
rent RLN. In such cases, vagal stimulation high in the neck results in
laryngeal EMG activity, but stimulation low in the neck below the lar-
ynx and below the RLN branch point does not. We have used such
stimulation to diagnose nonrecurrence of the right RLN before the
nerve is directly visualized.
POSTOPERATIVE COMPLICATIONS OF GOITER
SURGERY
Recurrent Laryngeal Nerve
RLN paralysis rates vary significantly from study to study, but in general,
they are consistently higher when surgery is performed for goiter as com-
pared with routine thyroidectomy. It is encouraging to note that in highly
skilled hands, even recurrent substernal goiter can be surgically removed
with very low complication rates, as noted by Australian workers.180 In
our series, the rate of RLN permanent paralysis was zero, and the rate of
transient paralysis was 2.5% of procedures and 1.8% of nerves at risk, all
resolving within 7 months.85 Sinclair, while noting a 1.1% permanent
RLN paralysis rate overall in his series of 767 thyroid surgeries, described
a 17.5% rate with substernal goiter, associated with a policy of not iden-
tifying the RLN before goiter delivery.192 Hockauf and Saylor, in treating
1713 patients with goiter, noted a 6.8% rate of permanent RLN paralysis
for goiter overall and a 27% rate of RLN paralysis with substernal goi-
ter.216 MacIntosh described a 10% rate of RLN paralysis with substernal
goiter.217 In a German multicenter study of 7266 patients with benign
goiter, Thomusch found transient RLN paralysis occurred in 2.1% of
patients and permanent RLN paralysis in 1.1%. Bilateral RLN transient
paralysis occurred in 0.002% and bilateral RLN permanent paralysis in
0.001%.218 Shen, in a surgical series of 60 patients with substernal goiter,
found 12% had airway complications postoperatively but did not provide
information regarding postoperative laryngeal examination in these
patients.219 Rios-Zambudio, in 301 patients with goiter operated on by
experienced endocrine surgeons, found RLN injury occurred in 8.6%
of patients and was more likely in patients with hyperthyroidism and
in those with larger and substernal goiters. Again, routine laryngoscopy
was not performed.220 In our series, laryngeal nerve monitoring was
associated with a significant decreased risk of RLN paralysis by 87%.
Analysis of risk factors in our series revealed that RLN paralysis during
goiter surgery found that increased RLN risk was predicted by the pres-
ence of bilateral cervical goiter, but not by size, presence of revision sur-
gery, substernal extension, or preoperative compressive symptoms. We
also confirmed that retrotracheal goiter and posterior mediastinal goiter,
when identified on preoperative CT scan, can help predict a ventrally dis-
placed RLN, which is at extremely high risk during surgery.85
Parathyroid Glands
Rates of hypoparathyroidism vary significantly between series in goiter
surgery. Rates in expert hands as low as 1% to 1.5% have been
reported.88,218 Thomusch found that transient parathyroid hypofunction
occurred in 6.4% of patients, and permanent parathyroid dysfunction
occurred in 1.5% of patients in his multicenter study on benign goiter.
There was a correlation between long-term hypoparathyroidism and
extent of thyroid resection.218 We found permanent hypoparathyroidism
in 8% of patients undergoing bilateral surgery and in 3% of patients over-
all, including patients with revision surgery.85 Hypothyroidism can be
expected based on degree of thyroid resection, dietary iodine status,
and presence of autoimmune thyroid antibodies.
Risk Factors for Complications During Goiter Surgery
Several series suggest an increased risk of both RLN and parathyroid
complications for substernal versus cervical goiter.192,216 Lo, Kwok,
and Yuen found increased RLN risk during goiter surgery with longer
operative procedures and those associated with increased blood
loss.221 Torre et al. found increased risk if substernal goiter had a
“complex endothoracic” relationship or if total thyroidectomy was
performed.8 Agerback et al. found increased RLN risk with increasing
goiter size.209 Calik et al. found increased risk to both the RLN and
parathyroids with recurrent goiter, cases associated with thyroid can-
cer with nodal resection, and thyroiditis.222 Judd, Beahrs, and Bowes
found an increased overall complication rate in patients requiring
sternotomy.96 In our series, we identified a number of other factors
that are important in the conduct of surgery, including degree of cap-
sular blood vessel engorgement and friability, goiter consistency, and
compressibility.85
Thomusch, in a German multicenter study, provided a multivariate
analysis of complications that occurred during benign goiter surgery in
7266 patients.218 Using logistical regression analysis, RLN injury was
found to be associated with (1) extent of surgery, (2) recurrent goiters,
and (3) failure to identify the RLN. It is of interest that failure to identify
the nerve resulted in a 9.9-fold increase of nerve paralysis for patients
undergoing total thyroidectomy. Hypoparathyroid complications were
found to be associated with (1) extent of resection, (2) recurrent goiters,
(3) age, (4) gender (female more than male), (5) volume of thyroid sur-
gery done in the hospital, and (6) presence of Graves’ disease. Also
interesting was Thomusch’s finding that, unlike RLN identification,
the identification of at least one parathyroid gland during the goiter
surgery did not affect the rate of postoperative hypoparathyroidism.218
Other Complications
Please see the Expert Consult website for more discussion of this topic.
Tracheomalacia
Tracheomalacia is poorly understood, extremely rare, and apparently
reversible. Geelhoed and Green et al. have reported tracheomalacia
after goiter surgery.230,231 The incidence of tracheomalacia has previ-
ously been estimated to be between 0.001% and 1.5%.95,231,232 Of note,
Sitges-Serra and Sancho, in reviewing six major studies, found two
cases of what they believed was tracheomalacia.95 In 72 patients with
substernal goiters, Rodriguez noted no cases of tracheomalacia.88
McHenry and Protrowski, Mellière et al., Shaha et al., and Wade
found no cases of tracheomalacia in their series.5,56,105,233 In our com-
bined series of 200 large cervical and substernal goiters treated at Mas-
sachusetts Eye and Ear Infirmary and Massachusetts General
Hospital, we did not come across a single case of tracheomalacia from
benign goiter, even in the setting of chronic significant tracheal devi-
ation, compression, and remodeling with massive and recurrent goi-
ters. Tracheotomy was performed in only 3% of patients, and in none
of these cases was it performed for tracheomalacia.85 In all cases the
trachea can be evaluated directly through the wound to determine
whether there is evidence of poor tracheal integrity or dynamic
change with the respiratory cycle. We have seen cases that were
referred with a presumptive diagnosis of tracheomalacia that ulti-
mately were found to have bilateral vocal cord paralysis that had
not been recognized. It is our strong clinical impression that tracheo-
malacia from goiter is rare and likely has arisen as a diagnostic error
for underlying bilateral vocal cord paralysis. We do not advocate rou-
tine postsurgical bronchoscopy or prophylactic tracheotomy. If
68.e1
Other Complications
Very limited information is available regarding SLN paralysis during
goiter surgery, although Calik et al. described a rate of 1.1%.223 The
overall prevalence of SLN injury in thyroid surgery is difficult to assess
given the often vague vocal findings and subtle findings on laryngos-
copy postoperatively (requiring need for postoperative cricothyroid
muscle EMG for definitive diagnosis), with a wide range of rates
reported in the literature from 0% to 58%.224 Large goiters and superior
extent of goiter, however, are reported risk factors for SLN injury given
the increased proximity of the superior pole to the nerve.225 Serious
intraoperative bleeding is reported in 0.5% to 5.5% of cases of cervical
and substernal goiter.8,20,223 Mediastinal hematoma, in a literature
review by Singh, Lucente, and Shaha, is reported in 3% of patients with
substernal goiter.89 Pneumothorax has been reported in from 1.4% to
5.3% of cases.25,226 Wound infection is reported in 1.8% of patients.223
Cho, Cohen, and Som noted a single patient with esophageal laceration
as a result of substernal goiter surgery.25 Others have described low
rates of atrial fibrillation, pleural effusion, and Horner’s syndrome.
Air embolism was reported by Pemberton in 1921.38 Chyle fistula
was reported by Lahey in 1936.227 The rate of tracheotomy has been
reported as ranging from 2.1% to 13%.8,20,228,229 Tracheotomy may
be due to bilateral vocal cord paralysis or airway edema, or performed
for nonairway issues (pulmonary toilette) or prophylactically. The mor-
tality rate after goiter surgery is low. Torre et al. noted a 0.8% rate in
their series of more than 200 substernal goiters. One patient had an
advanced mediastinal malignancy.8
In our series of 200 thyroidectomies for goiter, complications other
than hypoparathyroidism and RLN injury included one episode of
hemorrhage requiring ligation of a bleeding vessel in the operating
room and one episode of subglottic stenosis, eventually requiring tra-
cheotomy in a multiple revision patient. We also encountered one case
of atrial fibrillation postoperatively in a previously euthyroid patient
and two cases of dysphagia after resection of masses causing tracheal
deviation or compression.85
 CHAPTER 6 Surgery of Cervical and Substernal Goiter 69

tracheomalacia exists as a diagnostic entity from chronic goiter RECURRENT GOITER: PREVENTION AND
compression, it is unclear how a trachea that has been rendered sig-
nificantly structurally insufficient (i.e., floppy) by chronic goiter com- TREATMENT
pression would become structurally intact by a short-term intubation. Please see the Expert Consult website for more discussion of this topic.
A variety of recommendations have been made regarding the treat-
ment of tracheomalacia, including intubation, tracheotomy, Marlex
mesh of the trachea, tracheopexy, and various types of tracheal
REFERENCES
grafting. For a complete list of references, go to expertconsult.com.

RECURRENT GOITER: PREVENTION AND
TREATMENT
The administration of thyroid hormone as a preventive method against
goiter recurrence is controversial (see Chapter 9, Reoperation for
Benign Thyroid Disease). Thyroid hormone suppressive therapy has
also been used to prevent goiter recurrence after less than total thyroid-
ectomy. Several studies showing benefit to T4 treatment were nonran-
domized.182,234,235 Miccoli showed benefit in a prospective randomized
study but without an adequate control group and a follow-up of only
3 years. “Recurrence” in this study was defined as the sonographic
reappearance of nodules, not clinical recurrence.236 Several studies
show no difference in goiter recurrence with or without T4 treat-
ment.10,178,179,181,237 Bistrup, in a randomized, prospective, nonpla-
cebo, controlled study with a 9-year follow-up, found no significant
effect of T4 in preventing postoperative goiter recurrence.178 Hegedus,
Nygaard, and Hansen, in 202 patients with a 12-year follow-up, found
no statistically significant benefit to T4 suppressive therapy in goiter
recurrence.10 Interestingly, Hegedus found increased goiter recurrence
in patients who had larger goiter specimens removed, in those with
larger remnants left in situ (24-mL remnant with recurrence versus
18-mL remnant without recurrence), and in those with lower postop-
erative TSH (TSH 1.6 μg/dL with recurrence versus 2.2 μg/dL without
recurrence). Patients from iodine-deficient regions and those with a
history of past radiation therapy may represent responders in terms
of T4 prevention of recurrent goiter formation.10,178 We believe that
uncertainty regarding the efficacy of T4 suppressive therapy coupled
with the known skeletal and cardiac effects of subclinical
69.e1
hyperthyroidism make routine postoperative T4 suppression unwar-
ranted. TSH is only one of many follicular growth factors. Radioiodine
treatment may be considered in recurrent goiter cases to prevent reo-
perative surgery, particularly in patients with a history of multiple
recurrences.
Recurrent goiter presentation is similar to initial goiter presentation
except that past perithyroidal scarring may restrict thyroid growth and
more readily result in compressive aerodigestive tract symptoms. Vocal
cord paralysis and recurrent thyroid masses require consideration of
malignant infiltration versus injury from past surgery. Past surgical
operative notes and pathology reports should be reviewed. Operative
notes may detail key information regarding location of the RLN and
remaining parathyroid glands (see Chapter 9, Reoperation for Benign
Thyroid Disease). The RLN, through an inferior approach, may allow
identification of the nerve in a relatively undissected region, depending
on the extent of past surgery (see Chapter 36, Surgical Anatomy and
Monitoring of the Recurrent Laryngeal Nerve). When operating on a
contralateral lesion (relative to past thyroid surgery), one should con-
servatively assume, despite operative notes to the contrary, that both
parathyroids from the first surgery have been removed. At the begin-
ning of surgery, bilateral inferior jugular parathyroid hormone (PTH)
sampling may provide further information regarding parathyroid func-
tion on each side of the neck. Risks of reoperative goiter surgery are
emphasized in the literature, which documents RLN permanent paral-
ysis from 3% to 18% and permanent hypoparathyroidism in 0% to 25%
of patients.180-183,238-240 In our series of 200 thyroidectomies for goiter,
revision surgery was, however, not more likely to be associated with
postoperative complications than first-time surgery.85
69.e2
1. Lawson VC. Multinodular goiter. In: Falk SA, ed. Thyroid Disease.
New York: Raven Press; 1990.
2. Pulli RS, Coniglio JV. Surgical management of substernal goiter.
Laryngoscope. 1998;108:358.
3. Halsted WS. Operative story of goiter: the author’s operation. Johns
Hopkins Hospital Report. 1920;108:71.
4. G€unther GB. Operative Behandlung des kroptes (Struma). In: Lehre von
den Blutigen Operationen am Menschlichen K€ orpen. Leipzig; 1964.
5. McHenry CR, Piotrowski JJ. Thyroidectomy in patients with marked
thyroid enlargement: airway management, morbidity, and outcome. Am
Surg. 1994;60(8):586–591.
6. Russell C. Management of benign non-endemic goiter. In: Duh Q-Y,
Clark OH, eds. Textbook of Endocrine Surgery. Philadelphia, PA: WB
Saunders; 1997.
7. Clark OH. Total thyroidectomy: the treatment of choice for patients with
differentiated thyroid cancer. Ann Surg. 1982;196(3):361–370.
8. Torre G, Borgonovo G, Amato A, et al. Surgical management of substernal
goiter: analysis of 237 patients. Am Surg. 1995;61(9):826–831.
9. Miller MR, Pincock AC, Oates GD, Wilkinson R, Skene-Smith H. Upper
airway obstruction due to goitre: detection, prevalence and results of
surgical management. Q J Med. 1990;74(274):177–188.
10. Hegedus L, Nygaard B, Hansen JM. Is routine thyroxine treatment to
hinder postoperative recurrence of nontoxic goiter justified? J Clin
Endocrinol Metab. 1999;84(2):756–760.
11. Katlic MR, Grillo HC, Wang CA. Substernal goiter. Analysis of 80
patients from Massachusetts General Hospital. Am J Surg. 1985;149(2):
283–287.
12. Shin JJ, Grillo HC, Mathisen D, et al. Surgical management of goiter: Part I:
preoperative assessment. Laryngoscope. 2011;121(1):60–67.
13. Manoppo AE. Resection of an unusually large goitre. Br J Surg.
1977;64(3):158–159.
14. Dunn JT, Medeiros-Neto GA. Endemic goiter and cretinism: continuing
threats to world health. Vol. 292. Pan American Health Organization;
1974:1.
15. Perez C, Scrimshaw NS, Munoz JA. Technique of endemic goiter surveys.
endemic goiter. Geneva: World Health Organization; 1960.
16. World Health Organization. United Nations Children’s Fund, International
Council for the Control of Iodine Deficiency Disorders. Indicators for
Assessing Iodine Deficiency Disorders and Their Control Through Salt
Iodization. Geneva: World Health Organization; 1994.
17. Lahey FH, Swinton NW. Intrathoracic goiter. Surg Gynecol Obstet. 1934;59.
18. Crile GC. Intrathoracic goiter. Cleve Clin Q. 1939;6:313–322.
19. Goldenberg IS, Lindskog GE. Differential diagnosis, pathology, and
treatment of substernal goiter. JAMA. 1957;163(7):527–529.
20. Sanders LE, et al. Mediastinal goiters. The need for an aggressive approach.
Arch Surg. 1992;127(5):609–613.
21. DeCourcy JL, Price CA. Intrathoracic goiter: case report. Am J Surg.
1944;64(2):257–262.
22. Johnston JH Jr, Twente GE. Surgical approach to intrathoracic
(mediastinal) goiter. Ann Surg. 1956;143(5):572–579.
23. Wakeley CP, Mulvany JH. Intrathoracic goiter. Surg Gynecol Obstet.
1940;70:702–710.
24. Higgins CC. Intrathoracic goiter. Arch Surg. 1927;15(6):895–912.
25. Cho HT, Cohen JP, Som ML. Management of substernal and intrathoracic
goiters. Otolaryngol Head Neck Surg. 1986;94(3):282–287.
26. Shahian DM, Rossi RL. Posterior mediastinal goiter. Chest. 1988;94(3):
599–602.
27. Shahian DM. Surgical treatment of intrathoracic goiter. In: Randolph G,
Cady B, eds. Surgery of the Thyroid and Parathyroid Glands. Philadelphia:
WB Saunders; 1991.
28. Brown BM, Oshita AK, Castellino RA. CT assessment of the adult
extrathoracic trachea. J Comput Assist Tomogr. 1983;7(3):415–418.
29. DeAndrade MA. A review of 128 cases of posterior mediastinal goiter.
World J Surg. 1997;1(6):789–797.
30. Sweet RH. Intrathoracic goiter located in the posterior mediastinum.
Surg Gynecol Obstet. 1949;89(1):57–66.
31. Madjar S, Weissberg D. Retrosternal goiter. Chest. 1995;108(1):78–82.
32. Rietz KA, Werner D. Intrathoracic goiter. Acta Chir Scand.
1960;119:379–388.
33. Buckley JA, Stark P. Intrathoracic mediastinal thyroid goiter: imaging
manifestations. AJR Am J Roentgenol. 1999;173(2):471–475.
34. Ellis FH Jr, Good CA, Seybold WD. Intrathoracic goiter. Ann Surg.
1952;135(1):79–90.
35. Crohn NN, Kobak MW. True posterior mediastinal goiter. Am J Surg.
1951;82(2):283–286.
36. Falor WH, Kelly TR, Jackson JB. Intrathoracic goiter. Surg Gynecol Obstet.
1963;117:604–610.
37. Rives JD. Mediastinal aberrant goiter. Ann Surg. 1947;126(5):797–810.
38. Pemberton J. Surgery of substernal and intrathoracic goiter. Arch Surg.
1921;2.
39. McCort J. Intrathoracic goiter; its incidence, symptomatology, and
roentgen diagnosis. Radiology. 1949;53(2):227–237.
40. Falor WH, Kelly TR, Krabill WS. Intrathoracic goiter. Ann Surg.
1955;142(2):238–247.
41. Hall TS, Caslowitz P, Popper C, Smith GW. Substernal goiter versus
intrathoracic aberrant thyroid: a critical difference. Ann Thorac Surg.
1988;46(6):684–685.
42. Nwato DL. Heterotopic mediastinal goiter. Br J Surg. 1978;65(7):505–506.
43. Lawson W, Biller HF. Management of substernal thyroid disease.
In: Falk SA, ed. Thyroid Disease. New York: Raven Press; 1990.
44. Livolsi VA. Surgical pathology of the thyroid. In: Major Problems in
Pathology. Philadelphia: Saunders; 1990:xvi.
45. Gittoes NJ, Miller MR, Daykin J, Sheppard MC, Franklyn JA. Upper
airways obstruction in 153 consecutive patients presenting with thyroid
enlargement. BMJ. 1996;312(7029):484.
46. Andersson M, et al. Iodine Status Worldwide. WHO Global Database on
Iodine Deficiency: Department of Nutrition for Health and Development.
Geneva: World Health Organization; 2004.
47. Hurley DL, Gharib H. Evaluation and management of multinodular goiter.
Otolaryngol Clin North Am. 1996;29(4):527–540.
48. Mazzaferri EL. Management of a solitary thyroid nodule. N Engl J Med.
1993;328(8):553–559.
49. DeLange F. Iodine deficiency. In: Braverman LE, Utiger RD, eds. Werner
and Ingbar’s The Thyroid. 8th ed. Philadelphia: Lippincott Williams &
Wilkins; 2000.
50. Cheung PS. Medical and surgical treatment of an endemic goiter.
In: Clark O, Duh Q-Y, eds. Textbook of Endocrine Surgery. Philadelphia:
WB Saunders; 1997.
51. Pinchera A, Aghini-Lombardi F, Antonangeli L, Vitti P. Multinodular
goiter. Epidemiology and prevention. Ann Ital Chir. 1996;67(3):317–325.
52. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to
nonpalpable nodules discovered incidentally on thyroid imaging. Ann
Intern Med. 1997;126(3):226–231.
53. Reeve TS, Rubinstein CE, Rundle FF. Intrathoracic goitre: its prevalence in
Sydney metropolitan mass x-ray surgery. Med J Aust. 1957;44(5):149–156.
54. Rundle FF, Delampert RN, Epps RG. Cervical thoracic tumors: the
technique aiding in their roentgenologic location. Am J Public Health.
1959;49:316.
55. Fritts L, Thompson NW. The surgical treatment of substernal goiter.
In: Friedman M, ed. Operative Techniques in Otolaryngology Head and
Neck Surgery. Philadelphia: WB Saunders; 1994.
56. Allo MD, Thompson NW. Rationale for the operative management of
substernal goiters. Surgery. 1983;94(6):969–977.
57. Sand ME, Laws HL, McElvein RB. Substernal and intrathoracic goiter.
Reconsideration of surgical approach. Am Surg. 1983;49(4):196–202.
58. Mellière D, Saada F, Etienne G, Becquemin JP, Bonnet F. Goiter with severe
respiratory compromise: evaluation and treatment. Surgery. 1988;103(3):
367–373.
59. Pemberton JD. Surgery of substernal and intrathoracic goiter. Arch Surg.
1955;71.
60. Newman E, Shaha AR. Substernal goiter. J Surg Oncol. 1995;60(3):207–212.
61. Wychulis AR, Payne WS, Clagett OT, Woolner LB. Surgical treatment of
mediastinal tumors: a 40 year experience. J Thorac Cardiovasc Surg.
1971;62(3):379–392.
62. Dumont JE, et al. Large goitre as a maladaptation to iodine deficiency. Clin
Endocrinol (Oxf). 1995;43(1):1–10.
63. Foley TP Jr. Goiter in adolescents. Endocrinol Metab Clin North Am.
1993;22(3):593–606.

64. Derwahl M, Broecker M, Kraiem Z. Clinical review 101: thyrotropin may
not be the dominant growth factor in benign and malignant thyroid
tumors. J Clin Endocrinol Metab. 1999;84(3):829–834.
65. Derwahl M, Studer H. Multinodular goitre: “much more to it than simply
iodine deficiency”. Baillieres Best Pract Res Clin Endocrinol Metab.
2000;14(4):577–600.
66. Studer H, Derwahl M. Mechanisms of nonneoplastic endocrine
hyperplasia—a changing concept: a review focused on the thyroid gland.
Endocr Rev. 1995;16(4):411–426.
67. Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: the
basis for understanding thyroid function and nodular goiter growth.
Endocr Rev. 1989;10(2):125–135.
68. Kopp P, Kimura ET, Aeschimann S, et al. Polyclonal and monoclonal
thyroid nodules coexist within human multinodular goiters. J Clin
Endocrinol Metab. 1994;79(1):134–139.
69. Dremier S, Copp
ee F, Delange F, Vassart G, Dumont JE, Van Sande J.
Clinical review 84: thyroid autonomy: mechanism and clinical effects.
J Clin Endocrinol Metab. 1996;81(12):4187–4193.
70. Derwahl M, Hamacher C, Russo D, et al. Constitutive activation of the Gs
alpha protein-adenylate cyclase pathway may not be sufficient to generate
toxic thyroid adenomas. J Clin Endocrinol Metab. 1996;81(5):1898–1904.
71. Krohn K, F€ uhrer D, Bayer Y, et al. Molecular pathogenesis of euthyroid and
toxic multinodular goiter. Endocr Rev. 2005;26(4):504–524.
72. Paschke R. Molecular pathogenesis of nodular goiter. Langenbecks Arch
Surg. 2011;396(8):1127–1136.
73. Kopp P, van Sande J, Parma J, et al. Brief report: congenital
hyperthyroidism caused by a mutation in the thyrotropin-receptor gene.
N Engl J Med. 1995;332(3):150–154.
74. Meier CA. Molecular endocrinology of thyroid diseases. Schweiz Med
Wochenschr. 1995;125(49):2367–2378.
75. Berghout A, Wiersinga WM, Drexhage HA, Smits NJ, Touber JL.
Comparison of placebo with L-thyroxine alone or with carbimazole for
treatment of sporadic non-toxic goitre. Lancet. 1990;336(8709):193–197.
76. Smallridge RC. Metabolic and anatomic thyroid emergencies: a review.
Crit Care Med. 1992;20(2):276–291.
77. Elte JW, Bussemaker JK, Haak A. The natural history of euthyroid
multinodular goitre. Postgrad Med J. 1990;66(773):186–190.
78. Lahey F. Intrathoracic goiter. Surg Clin North Am. 1945;25.
79. Case records of Massachusetts General Hospital, C.N. N Engl J Med.
1936;215.
80. Miller RB. Large intrathoracic thyroid. Am J Roentgenol. 1938;40.
81. Soley MH, Reinhart JF. Intrathoracic goiter stimulating right sided cardiac
enlargement. Am Heart J. 1939;18.
82. Maberly GF, Corcoran JM, Eastman CJ. The effect of iodized oil on goitre
size, thyroid function and the development of the Jod Basedow
phenomenon. Clin Endocrinol (Oxf). 1982;17(3):253–259.
83. Jarløv AE, Heged€ us L, Gjørup T, Hanssen JE. Accuracy of the clinical
assessment of thyroid size. Dan Med Bull. 1991;38(1):87–89.
84. Cohen JD, Cho HT. Surgery for substernal goiter. In: Friedman M, ed.
Operative Techniques in Otolaryngology Head and Neck Surgery.
Philadelphia: WB Saunders; 1994.
85. Randolph GW, Shin JJ, Grillo HC, et al. The surgical management
of goiter: Part II: surgical treatment and results. Laryngoscope.
2011;121(1):68–76.
86. Michel LA, Bradpiece HA. Surgical management of substernal goitre.
Br J Surg. 1988;75(6):565–569.
87. Michel LA. Surgery of substernal goiter. Acta Otorhinolaryngol Belg.
1987;41(5):863–880.
88. Rodriguez JM, et al. Substernal goiter: clinical experience of 72 cases.
Ann Otol Rhinol Laryngol. 1999;108(5):501–504.
89. Singh B, Lucente FE, Shaha AR. Substernal goiter: a clinical review.
Am J Otolaryngol. 1994;15(6):409–416.
90. Shaha AR, Alfonso AE, Jaffe BM. Operative treatment of substernal goiters.
Head Neck. 1989;11(4):325–330.
91. Maruotti RA, Zannini P, Viani MP, Voci C, Pezzuoli G. Surgical treatment
of substernal goiters. Int Surg. 1991;76(1):12–17.
92. Wax MK, Briant TD. Management of substernal goitre. J Otolaryngol.
1992;21(3):165–170.
69.e3
93. White ML, Doherty GM, Gauger PG. Evidence-based surgical
management of substernal goiter. World J Surg. 2008;32:1285–1300.
94. Anders HJ. Compression syndromes caused by substernal goitres. Postgrad
Med J. 1998;74(872):327–329.
95. Sitges-Serra A, Sancho J. Surgical management of recurrent and
intrathoracic goiter. In: Clark O, Duh Q-Y, eds. Textbook of Endocrine
Surgery. Philadelphia: WB Saunders; 1997.
96. Judd ES, Beahrs OH, Bowes DE. A consideration of the proper surgical
approach for substernal goiter. Surg Gynecol Obstet. 1960;110:90–98.
97. Georgiadis N, Katsas A, Leoutsakos B. Substernal goiter. Int Surg.
1970;54(2):116–121.
98. Torres A, Arroyo J, Kastanos N, Estopá R, Rabaseda J, Agustí-Vidal A.
Acute respiratory failure and tracheal obstruction in patients with
intrathoracic goiter. Crit Care Med. 1983;11(4):265–266.
99. Bodon GR, Piccoli AJ. Intrathoracic goiter with hemorrhage causing severe
respiratory distress. Am J Surg. 1957;93(6):1026–1029.
100. Morl M, Bartels O. Acute respiratory insufficiency caused by plunging
goiter (author’s transl). Med Klin. 1975;70(22):981–983.
101. Cougard P, Matet P, Goudet P, et al. Substernal goiters. 218 operated cases.
Ann Endocrinol (Paris). 1992;53(5-6):230–235.
102. Alfonso A, Christoudias G, Amaruddin Q, Herbsman H, Gardner B.
Tracheal or esophageal compression due to benign thyroid disease.
Am J Surg. 1981;142(3):350–354.
103. Hillerdal G, Aust R, Dubiel WT, Nordin U, Victorin A. Intrathoracic goitre
with the superior vena cava syndrome, hoarseness and acute stridor.
ORL J Otorhinolaryngol Relat Spec. 1979;40(6):340–345.
104. Warren CP. Acute respiratory failure and tracheal obstruction in the
elderly with benign goitres. Can Med Assoc J. 1979;121(2):191–194.
105. Shaha AR, Burnett C, Alfonso A, Jaffe BM. Goiters and airway problems.
Am J Surg. 1989;158(4):378–380; discussion 380–381.
106. Stauffer JL, Olson DE, Petty TL. Complications and consequences of
endotracheal intubation and tracheotomy. A prospective study of 150
critically ill adult patients. Am J Med. 1981;70(1):65–76.
107. Pearson FG, Goldberg M, da Silva AJ. Tracheal stenosis complicating
tracheostomy with cuffed tubes. Clinical experience and observations from
a prospective study. Arch Surg. 1968;97(3):380–394.
108. Mackle T, Meaney J, Timon C. Tracheoesophageal compression associated
with substernal goitre. Correlation of symptoms with cross-sectional
imaging findings. J Laryngol Otol. 2007;121(4):358–361.
109. Stang MT, Armstrong MJ, Ogilvie JB, et al. Positional dyspnea and tracheal
compression as indications for goiter resection. Arch Surg. 2012;147(7):
621–626.
110. Hedayati N, McHenry CR. The clinical presentation and operative
management of nodular and diffuse sub-sternal thyroid disease. Am Surg.
2002;68:245–251.
111. Bonnema SJ, Bertelsen H, Mortensen J, et al. The feasibility of high dose
iodine 131 treatment as an alternative to surgery in patients with a very
large goiter: effect on thyroid function and size and pulmonary function.
J Clin Endocrinol Metab. 1999;84(10):3636–3641.
112. Karbowitz SR, Edelman LB, Nath S, Dwek JH, Rammohan G. Spectrum of
advanced upper airway obstruction due to goiters. Chest. 1985;87(1):18–21.
113. Hoffstein V. Relationship between lung volume, maximal expiratory flow,
forced expiratory volume in one second, and tracheal area in normal men
and women. Am Rev Respir Dis. 1986;134(5):956–961.
114. Jauregui R, Lilker ES, Bayley A. Upper airway obstruction in euthyroid
goiter. JAMA. 1977;238(20):2163–2166.
115. Cooper JC. The use of CT in the evaluation of large multinodular goiters.
Am R Coll Surg Engl. 1971;73(32).
116. Melissant CF, Smith SJ, Perlberger R, Verschakelen J, Lammers JW,
Demedts M. Lung function, CT-scan and X-ray in upper airway
obstruction due to thyroid goitre. Eur Respir J. 1994;7(10):1782–1787.
117. Barker P, Mason RA, Thorpe MH. Computerised axial tomography of
the trachea. A useful investigation when a retrosternal goitre causes
symptomatic tracheal compression. Anaesthesia. 1991;46(3):195–198.
118. McCort JJ. Intrathoracic goiter; its incidence, symptomatology, and
roentgen diagnosis. Radiology. 1949;53(2):227–237.
119. Dekker E, Ledeboer RC. Compression of the tracheobronchial tree by the
action of the voluntary respiratory musculature in normal individuals and
69.e4
in patients with asthma and emphysema. Am J Roentgenol Radium Ther
Nucl Med. 1961;85:217–228.
120. Hilton HD, Griffin WT. Posterior mediastinal goiter. Am J Surg.
1968;116(6):891–895.
121. Chen AY, Bernet VJ, Carty SE, et al. American Thyroid Association
statement on optimal surgical management of goiter. Thyroid.
2014;24(2):181–189.
122. Glazer GM, Axel L, Moss AA. CT diagnosis of mediastinal thyroid. AJR Am
J Roentgenol. 1982;138(3):495–498.
123. Yousem DM, Scheff AM. Thyroid and parathyroid gland pathology. Role
of imaging. Otolaryngol Clin North Am. 1995;28(3):621–649.
124. Bashist B, Ellis K, Gold RP. Computed tomography of intrathoracic goiters.
AJR Am J Roentgenol. 1983;140(3):455–460.
125. Weber AL, Randolph G, Aksoy FG. The thyroid and parathyroid glands:
CT and MR imaging and correlation with pathology and clinical findings.
Radiol Clin North Am. 2000;38(5):1105–1129.
126. Blardinelli L, Gualdi G, Ceroni L, Guadalaxara A, Polettini E,
Pappalardo G. Comparison between CT and MR data and pathologic
findings in substernal goiter. Int Surg. 1995;80(1):65–69.
127. Mancuso AA, Dillon WP. The neck. Radiol Clin North Am.
1989;27(2):407–434.
128. Henneman G: Multinodular goiter. In: De Groot LJ, ed. Thyroid Disease
Manager [website]. Updated April 2017. Available at: www.
thyroidmanager.org. Accessed February 22, 2019.
129. Lamke LO, Bergdahl L, Lamke B. Intrathoracic goitre: a review of 29 cases.
Acta Chir Scand. 1979;145(2):83–86.
130. Corvilain B, Van Sande J, Dumont JE, Bourdoux P, Ermans AM.
Autonomy in endemic goiter. Thyroid. 1998;8(1):107–113.
131. Stanbury JB, Ermans AE, Bourdoux P, et al. Iodine-induced
hyperthyroidism: occurrence and epidemiology. Thyroid. 1998;8(1):
83–100.
132. Fradkin JE, Wolff J. Iodide-induced thyrotoxicosis. Medicine (Baltimore).
1983;62(1):1–20.
133. Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations
as a risk factor for atrial fibrillation in older persons. N Engl J Med.
1994;331(19):1249–1252.
134. F€oldes J, Tarján G, Szathmari M, Varga F, Krasznai I, Horvath C. Bone
mineral density in patients with endogenous subclinical hyperthyroidism:
is this thyroid status a risk factor for osteoporosis? Clin Endocrinol (Oxf).
1993;39(5):521–527.
135. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid
Association management guidelines for adult patients with thyroid nodules
and differentiated thyroid cancer: the American Thyroid Association
Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid
Cancer. Thyroid. 2016;26(1):1–133.
136. Ross DS. Thyroid hormone suppressive therapy of sporadic nontoxic
goiter. Thyroid. 1992;2(3):263–269.
137. Nygaard B, Faber J, Veje A, Heged€ us L, Hansen JM. Transition of nodular
toxic goiter to autoimmune hyperthyroidism triggered by 131I therapy.
Thyroid. 1999;9(5):477–481.
138. Hermus AR, Huysmans DA. Treatment of benign nodular thyroid disease.
N Engl J Med. 1998;338(20):1438–1447.
139. Gharib H, James EM, Charboneau JW, Naessens JM, Offord KP,
Gorman CA. Suppressive therapy with levothyroxine for solitary thyroid
nodules. A double-blind controlled clinical study. N Engl J Med.
1987;317(2):70–75.
140. Lima N, Knobel M, Cavaliere H, Sztejnsznajd C, Tomimori E, Medeiros-
Neto G. Levothyroxine suppressive therapy is partially effective in treating
patients with benign, solid thyroid nodules and multinodular goiters.
Thyroid. 1997;7(5):691–697.
141. Zorrilla L, Tsai J, Freedman M. Airway obstruction due to goiter in older
patients. J Am Geriatr Soc. 1989;37(12):1153–1156.
142. Burgi UEA. Clinical manifestations and management of non-toxic diffuse
and nodular goiter. In: Braverman LE, Utiger RD, eds. Werner and Ingbar’s
The Thyroid: A Fundamental and Clinical Text. Philadelphia: Lippincott
Williams & Wilkins; 1996.
143. Badillo J, Shimaoka K, Lessmann EM, Marchetta FC, Sokal JE. Treatment
of nontoxic goiter with sodium liothyronine. A double-blind study. JAMA.
1963;184:29–36.
144. Perrild H, Hansen JM, Heged€ us L, et al. Triiodothyronine and thyroxine
treatment of diffuse non-toxic goitre evaluated by ultrasonic scanning.
Acta Endocrinol (Copenh). 1982;100(3):382–387.
145. Celani MF. Levothyroxine suppressive therapy in the medical management
of nontoxic benign multinodular goiter. Exp Clin Endocrinol.
1993;101(5):326–332.
146. Wilders-Truschnig MM, Warnkross H, Leb G, et al. The effect of treatment
with levothyroxine or iodine on thyroid size and thyroid growth
stimulating immunoglobulins in endemic goitre patients. Clin Endocrinol
(Oxf). 1993;39(3):281–286.
147. Wesche MF, Tiel-V Buul MM, Lips P, Smits NJ, Wiersinga WM. A
randomized trial comparing levothyroxine with radioactive iodine in the
treatment of sporadic non-toxic goiter. J Clin Endocrinol Metab. 2001;
86(3):998–1005.
148. Uzzan B, Campos J, Cucherat M, Nony P, Boissel JP, Perret GY. Effects on
bone mass of long term treatment with thyroid hormones: a meta-analysis.
J Clin Endocrinol Metab. 1996;81(12):4278–4289.
149. Faber J, Galloe AM. Changes in bone mass during prolonged subclinical
hyperthyroidism due to L-thyroxine treatment: a meta-analysis. Eur J
Endocrinol. 1994;130(4):350–356.
150. Schneider R, Schneider M, Reiners C, Schneider P. Effects of levothyroxine
on bone mineral density, muscle force, and bone turnover markers: a
cohort study. J Clin Endocrinol Metab. 2012;97(11):3926–3934.
151. Fast S, Bonnema SJ, Heged€ us L. The majority of Danish nontoxic goitre
patients are ineligible for Levothyroxine suppressive therapy. Clin
Endocrinol. 2008;69(4):653–658.
152. Shapiro B. Optimization of radioiodine therapy of thyrotoxicosis: what
have we learned after 50 years? J Nucl Med. 1993;34(10):1638–1641.
153. Fast S, Nielsen VE, Grupe P, et al. Prestimulation with recombinant human
thyrotropin (rhTSH) improves the long-term outcome of radioiodine
therapy for multinodular nontoxic goiter. J Clin Endocrinol Metab.
2012;97:2653–2660.
154. Nieuwlaat WA, Huysmans DA, van den Bosch HC, et al. Pretreatment with
a single, low dose of recombinant human thyrotropin allows dose
reduction of radioiodine therapy in patients with nodular goiter. J Clin
Endocrinol Metab. 2003;88(7):3121–3129.
155. Fast S, Heged€ us L, Grupe P, et al. Recombinant human thyrotropin-
stimulated radioiodine therapy of nodular goiter allows major reduction of
the radiation burden with retained efficacy. J Clin Endocrinol Metab.
2010;95:3719–3725.
156. Huysmans DA, Buijs WC, van de Ven MT, et al. Dosimetry and risk
estimates of radioiodine therapy for large, multinodular goiters. J Nucl
Med. 1996;37(12):2072–2079.
157. Huysmans DA, Hermus AR, Corstens FH, Barentsz JO, Kloppenborg PW.
Large, compressive goiters treated with radioiodine. Ann Intern Med.
1994;121(10):757–762.
158. Nygaard B, Heged€ us L, Ulriksen P, Nielsen KG, Hansen JM. Radioiodine
therapy for multinodular toxic goiter. Arch Intern Med. 1999;159(12):
1364–1368.
159. Verelst J, Bonnyns M, Glinoer D. Radioiodine therapy in voluminous
multinodular non-toxic goitre. Acta Endocrinol (Copenh). 1990;122(4):
417–421.
160. de Klerk JM, van Isselt JW, van Dijk A, et al. Iodine-131 therapy in sporadic
nontoxic goiter. J Nucl Med. 1997;38(3):372–376.
161. Le Moli R, Wesche MF, Tiel-Van Buul MM, Wiersinga WM. Determinants
of long-term outcome of radioiodine therapy of sporadic non-toxic goitre.
Clin Endocrinol (Oxf). 1999;50(6):783–789.
162. Nygaard B, Søes-Petersen U, Høilund-Carlsen PF, et al. Improvement of
upper airway obstruction after 131I-treatment of multinodular nontoxic
goiter evaluated by flow volume loop curves. J Endocrinol Invest.
1996;19(2):71–75.
163. Huysmans D, Hermus A, Edelbroek M, Barentsz J, Corstens F, Kloppenborg P.
Radioiodine for nontoxic multinodular goiter. Thyroid. 1997;7(2):235–239.
164. Takáts KI, Szabolcs I, F€oldes J, et al. The efficacy of long term thyrostatic
treatment in elderly patients with toxic nodular goitre compared to
radioiodine therapy with different doses. Exp Clin Endocrinol Diabetes.
1999;107(1):70–74.
165. White ML, Doherty GM, Gauger PG. Evidence-based surgical
management of substernal goiter. World J Surg. 2008;32(7):1285–1300.

166. Sahbaz NA, Tutal F, Aksakal N, et al. Cancer frequency in retrosternal
goiter. Am Surg. 2017;83(12):1390–1393.
167. Campbell MJ, Candell L, Seib CD, et al. Unanticipated thyroid cancer in
patients with substernal goiters: are we underestimating the risk? Ann Surg
Oncol. 2015;22(4):1214–1218.
168. Aasted A, Bertelsen S. Superior vena caval syndrome in benign mediastinal
goitre. Acta Chir Scand. 1981;147(6):405–408.
169. Fleig WE, Stange EF, Ditschuneit H. Upper gastrointestinal hemorrhage
from downhill esophageal varices. Dig Dis Sci. 1982;27(1):23–27.
170. Holl-Allen RT. Laryngeal nerve paralysis and benign thyroid disease. Arch
Otolaryngol. 1967;85(3):335–337.
171. Manning PB, Thompson NW. Bilateral phrenic nerve palsy associated with
benign thyroid goiter. Acta Chir Scand. 1989;155(8):429–431.
172. Hassard AD, Holland JG. Benign thyroid disease and upper airway
obstruction: case presentations, pathophysiology, and management.
J Otolaryngol. 1982;11(2):77–82.
173. Delbridge L, Guinea AI, Reeve TS. Total thyroidectomy for bilateral benign
multinodular goiter: effect of changing practice. Arch Surg. 1999;134(12):
1389–1393.
174. Perzik S. The place of total thyroidectomy in the management of 909
patients with thyroid disease. Am J Surg. 1976;132(4):480–483.
175. Barczy
nski M, Konturek A, Hubalewska-Dydejczyk A, Golkowski F,
Nowak W. Ten-year follow-up of a randomized clinical trial of total
thyroidectomy versus Dunhill operation versus bilateral subtotal
thyroidectomy for multinodular non-toxic goiter. World J Surg.
2018;42(2):384–392.
176. Kraimps JL, Marechaud R, Gineste D, et al. Analysis and prevention of
recurrent goiter. Surg Gynecol Obstet. 1993;176(4):319–322.
177. Cirocchi R, Trastulli S, Randolph J, et al. Total or near-total thyroidectomy
versus subtotal thyroidectomy for multinodular non-toxic goitre in adults.
Cochrane Database Syst Rev. 2015;(8). CD010370.
178. Bistrup C, Nielsen JD, Gregersen G, Franch P. Preventive effect of
levothyroxine in patients operated for non-toxic goitre: a randomized trial
of one hundred patients with nine years follow-up. Clin Endocrinol (Oxf).
1994;40(3):323–327.
179. Rojdmark J, Jarhult J. High long term recurrence rate after subtotal
thyroidectomy for nodular goitre. Eur J Surg. 1995;161(10):725–727.
180. Reeve TS, Delbridge L, Brady P, Crummer P, Smyth C. Secondary
thyroidectomy: a twenty-year experience. World J Surg. 1988;12(4):
449–453.
181. Geerdsen JP, Frolund L. Recurrence of nontoxic goitre with and without
postoperative thyroxine medication. Clin Endocrinol (Oxf). 1984;21(5):
529–533.
182. Anderson PE, Hurley PR, Rosswick P. Conservative treatment and long
term prophylactic thyroxine in the prevention of recurrence of
multinodular goiter. Surg Gynecol Obstet. 1990;171(4):309–314.
183. Pappalardo G, Guadalaxara A, Frattaroli FM, Illomei G, Falaschi P. Total
compared with subtotal thyroidectomy in benign nodular disease: personal
series and review of published reports. Eur J Surg. 1998;164(7):501–506.
184. Berghout A, Wiersinga WM, Drexhage HA, et al. The long-term outcome
of thyroidectomy for sporadic non-toxic goitre. Clin Endocrinol (Oxf).
1989;31(2):193–199.
185. Wadstr€ om C, Zedenius J, Guinea A, Reeve T, Delbridge L. Multinodular
goitre presenting as a clinical single nodule: how effective is
hemithyroidectomy? Aust N Z J Surg. 1999;69(1):34–36.
186. Cohen-Kerem R, Schachter P, Sheinfeld M, Baron E, Cohen O.
Multinodular goiter: the surgical procedure of choice. Otolaryngol Head
Neck Surg. 2000;122(6):848–850.
187. Reeve TS, Delbridge L, Cohen A, Crummer P. Total thyroidectomy. The
preferred option for multinodular goiter. Ann Surg. 1987;206(6):782–786.
188. Kocher T. Bericht u €ber weitere 250 Kropfexstirpationen. Schweiz Med
Wochenschr. 1889;19:33–44.
189. Gardiner KR, Russell CF. Thyroidectomy for large multinodular colloid
goitre. J R Coll Surg Edinb. 1995;40(6):367–370.
190. Netterville JL, Coleman SC, Smith JC, Smith MM, Day TA, Burkey BB.
Management of substernal goiter. Laryngoscope. 1998;108(11 Pt
1):1611–1617.
191. Koh KB, Chang KW. Carcinoma in multinodular goitre. Br J Surg.
1992;79(3):266–267.
69.e5
192. Sinclair IS. The risk to the recurrent laryngeal nerves in thyroid and
parathyroid surgery. J R Coll Surg Edinb. 1994;39(4):253–257.
193. Randolph GW, Wu CW, Dionigi G, et al. The International RLN Anatomic
Classification System. In: Randolph GW, ed. The Recurrent and Superior
Laryngeal Nerves. New York: Springer; 2016:125–138.
194. Ehrenhaft JL, Buckwalter JA. Mediastinal tumors of thyroid origin. Arch
Surg. 1955;71(3):347–356.
195. Ziter FM Jr. Roentgenogram of the month. Ectopic mediastinal thyroid. Dis
Chest. 1966;49(6):641–642.
196. Pitt LP. Aberrant posterior mediastinal goiter. A review of the literature
and report of a case. Am J Surg. 1962;103:397–399.
197. Cohen JP. Substernal goiters and sternotomy. Laryngoscope. 2009;119(4):
683–688.
198. Raffaelli M, De Crea C, Ronti S, Bellantone R, Lombardi CP. Substernal
goiters: incidence, surgical approach, and complications in a tertiary care
referral center. Head Neck. 2011;33(10):1420–1425.
199. Rugiu MG, Piemonte M. Surgical approach to retrosternal goitre: do we
still need sternotomy? Acta Otorhinolaryngol Ital. 2009;29(6):331–338.
200. deSouza FM, Smith PE. Retrosternal goiter. J Otolaryngol. 1983;12(6):
393–396.
201. Har-El G, Sundaram K. Powered instrumentation for transcervical
removal of gigantic intrathoracic thyroid. Head Neck. 2001;23(4):322–325.
202. Landreneau RJ, Nawarawong W, Boley TM, Johnson JA, Curtis JJ.
Intrathoracic goiter: approaching the posterior mediastinal mass. Ann
Thorac Surg. 1991;52(1):134–135; discussion 135–136.
203. Hammond EJ, Uthman BM, Reid SA, Wilder BJ, Ramsay RE. Vagus nerve
stimulation in humans: neurophysiological studies and
electrophysiological monitoring. Epilepsia. 1990;31(suppl 2):S51–S59.
204. al-Suliman NN, Graversen HP, Blichert-Toft M. Surgical treatment of
benign recurrent goiter. Technique, complications and permanent
sequelae. Ugeskr Laeger. 1994;156(2):165–169.
205. Lore JM Jr, Szymula NJ. Superior mediastinal exposure. Arch Otolaryngol.
1980;106(1):6–7.
206. Khan MN, Goljo E, Owen R, Park RC, Yao M, Miles BA. Retrosternal
goiter: 30-day morbidity and mortality in the transcervical and
transthoracic approaches. Otolaryngol Head Neck Surg. 2016;155(4):
568–574.
207. Friedman M, Toriumi DM, Grybauskas VT, Applebaum EL. Implantation
of a recurrent laryngeal nerve stimulator for the treatment of spastic
dysphonia. Ann Otol Rhinol Laryngol. 1989;98(2):130–134.
208. Leonetti JP, Mokarry VP, Fan Z, Warf P, Hudson E. Vagal nerve
monitoring during parapharyngeal space tumor removal. Skull Base Surg.
1994;4(4):213–218.
209. Eisele DW. Intraoperative electrophysiologic monitoring of the recurrent
laryngeal nerve. Laryngoscope. 1996;106(4):443–449.
210. Satoh I. Evoked electromyographic test applied for recurrent laryngeal
nerve paralysis. Laryngoscope. 1978;88(12):2022–2031.
211. Penry JK, Dean JC. Prevention of intractable partial seizures by
intermittent vagal stimulation in humans: preliminary results. Epilepsia.
1990;31(suppl 2):S40–S43.
212. Schachter SC, Saper CB. Vagus nerve stimulation. Epilepsia. 1998;39(7):
677–686.
213. Lundy DS, Casiano RR, Landy HJ, Gallo J, Gallo B, Ramsey RE. Effects
of vagal nerve stimulation on laryngeal function. J Voice. 1993;7(4):
359–364.
214. Uthman BM, Wilder BJ, Hammond EJ, Reid SA. Efficacy and safety of
vagus nerve stimulation in patients with complex partial seizures. Epilepsia.
1990;31(suppl 2):S44–S50.
215. Schneider R, Lorenz K, Machens A, Thanh PN, Randolph GW, Dralle H.
Continuous intraoperative neuromonitoring (CIONM) of the recurrent
laryngeal nerve. In: Randolph GW, ed. The Recurrent and Superior
Laryngeal Nerves. New York: Springer; 2016:169–183.
216. Hockauf H, Sailer R. Postoperative recurrent nerve palsy. Head Neck Surg.
1982;4(5):380–384.
217. McIntosh D. Thyroid tumor. J R Coll Surg Edinb. 1978;23(5):266–284.
218. Thomusch O, Machens A, Sekulla C, et al. Multivariate analysis of risk
factors for postoperative complications in benign goiter surgery:
prospective multicenter study in Germany. World J Surg. 2000;24(11):
1335–1341.
69.e6
219. Shen WT, Kebebew E, Duh QY, Clark OH. Predictors of airway
complications after thyroidectomy for substernal goiter. Arch Surg.
2004;139(6):656–659; discussion 659–660.
220. Ríos Zambudio A, Rodríguez González JM, Torregrosa P
erez NM, Piñero
Madrona A, Canteras Jordana M, Parrilla Paricio P. Hypoparathyroidism
and hypocalcemia following thyroid surgery of multinodular goiter.
Multivariant study of the risk factors. Med Clin (Barc). 2004;122(10):
365–368.
221. Lo CY, Kwok KF, Yuen PW. A prospective evaluation of recurrent
laryngeal nerve paralysis during thyroidectomy. Arch Surg. 2000;135(2):
204–207.
222. Agerbaek H, Pilegaard HK, Watt-Boolsen S, et al. Complications of 2,028
operations for benign thyroid disease. Quantitative significance of various
risk factors. Ugeskr Laeger. 1988;150(9):533–536.
223. Calik A, Kucuktulu U, Cinel A, Bilgin Y, Alhan E, Piskin B. Complications
of 867 thyroidectomies performed in a region of endemic goiter in Turkey.
Int Surg. 1996;81(3):298–301.
224. Barczy
nski M, Randolph GW, Cernea CR, et al. External branch of the
superior laryngeal nerve monitoring during thyroid and parathyroid
surgery: International Neural Monitoring Study Group standards guideline
statement. Laryngoscope. 2013;123(suppl 4):S1–S14.
225. Furlan JC, Cordeiro AC, Brandão LG. Study of some “intrinsic risk factors”
that can enhance an iatrogenic injury of the external branch of the superior
laryngeal nerve. Otolaryngol Head Neck Surg. 2003;128(3):396–400.
226. Picardi N, Di Rienzo M, Annunziata A, Bartolacci M, Relmi F.
Transclavicular approach for delivery of intrathoracic giant goiter.
An alternative surgical option. Ann Ital Chir. 1999;70(5):741–748.
227. Lahey FH. Intrathoracic goiter. Surg Gynecol Obstet. 1936;16.
228. Abdel Rahim AA, Ahmed ME, Hassan MA. Respiratory complications
after thyroidectomy and the need for tracheostomy in patients with a large
goitre. Br J Surg. 1999;86(1):88–90.
229. Shaha A, Alfonso A, Jaffe BM. Acute airway distress due to thyroid
pathology. Surgery. 1987;102(6):1068–1074.
230. Geelhoed GW. Tracheomalacia from compressing goiter: management
after thyroidectomy. Surgery. 1988;104(6):1100–1108.
231. Green WE, Shepperd HW, Stevenson HM, Wilson W. Tracheal collapse
after thyroidectomy. Br J Surg. 1979;66(8):554–557.
232. Peterson JL, Rovenstine EA. Tracheal collapse complicating
thyroidectomy: a case report. Curr Res Anesth Analg. 1936;15.
233. Wade JS. Cecil Joll Lecture, 1979. Respiratory obstruction in thyroid
surgery. Ann R Coll Surg Engl. 1980;62(1):15–24.
234. Bergfelt G, Risholm L. Postoperative thyroid hormone therapy in nontoxic
goitre. Acta Chir Scand. 1963;126:531–537.
235. Ibis E, Erbay G, Aras G, Akin A. Postoperative goitre recurrence rate in
Turkey. Acta Endocrinol (Copenh). 1991;125(1):33–37.
236. Miccoli P, Antonelli A, Iacconi P, Alberti B, Gambuzza C, Baschieri L.
Prospective, randomized, double-blind study about effectiveness of
levothyroxine suppressive therapy in prevention of recurrence after
operation: result at the third year of follow-up. Surgery. 1993;114
(6):1097–1101; discussion 1101–1102.
237. Berglund J, Bondesson L, Christensen SB, Larsson AS, Tibblin S.
Indications for thyroxine therapy after surgery for nontoxic benign goitre.
Acta Chir Scand. 1990;156(6-7):433–438.
238. Roher HD, Goretzki PE. Management of goiter and thyroid nodules in an
area of endemic goiter. Surg Clin North Am. 1987;67(2):233–249.
239. Levin KE, Clark AH, Duh QY, Demeure M, Siperstein AE, Clark OH.
Reoperative thyroid surgery. Surgery. 1992;111(6):604–609.
240. Wojtczak B, Barczy
nski M. Intermittent neural monitoring of the recurrent
laryngeal nerve in surgery for recurrent goiter. Gland Surg. 2016;5(5):
481–489.