EUROPEAN UROLOGY FOCUS 1 (2016) 223230

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Review Adrenal Glands

Management of the Incidental Adrenal Mass

Arun Z. Thomas a, Michael L. Blute Sr. b, Christian Seitz c, Mouhammed Amir Habra d,
Jose A. Karam a,*
a
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; b Department of Urology, Massachusetts General Hospital,
Boston, MA, USA; c Department of Urology, Medical University of Vienna, Vienna, Austria; d Department of Endocrine Neoplasia and Hormonal Disorders, The
University of Texas MD Anderson Cancer Center, Houston, TX, USA

Article info Abstract

Article history: Context: Incidentally discovered adrenal masses are becoming more common in clinical
Accepted December 11, 2015 practice.
Objective: To review the management of the incidental adrenal mass, including initial
Associate Editor: evaluation, surveillance, medical therapy, and surgical therapy.
James Catto Evidence acquisition: A literature search of English-language publications that included
the keywords adrenal incidentaloma and incidental adrenal mass was performed
through July 2015 using PubMed. Relevant original articles and guidelines on the
Keywords: management of the incidental adrenal mass were ultimately selected for analysis, with
Adrenal mass the consensus of all authors.
Evidence synthesis: Data from the manuscripts included in this review were synthe-
Adrenal incidentaloma
sized, and ndings were categorized into metabolic evaluation, imaging, biopsy, surgical
Adenoma considerations, and follow-up recommendations.
Carcinoma Conclusions: Ideally, management of patients with adrenal incidentalomas should
involve a multidisciplinary approach with experienced surgeons, radiologists, and
endocrinologists to determine whether such lesions are benign or malignant and
functional or nonfunctional and/or whether they require surgical resection.
Patient summary: Management of patients with adrenal incidentalomas should involve
a multidisciplinary approach with surgeons, radiologists, and endocrinologists to deter-
mine whether such lesions are benign or malignant and functional or nonfunctional and/
or whether they require surgical resection.
# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

* Corresponding author. The University of Texas MD Anderson Cancer Center, Department of

Urology, 1515 Holcombe Blvd, Unit 1373, Houston, TX 77030, USA. Tel. +1 713 792 3250;
Fax: +1 713 794 4824.
E-mail address: JAKaram@mdanderson.org (J.A. Karam).

increases with age (<1% in patients aged <30 yr and as high

1. Introduction
Adrenal incidentalomas (AIs) are defined as asymptomatic
masses >1 cm in diameter discovered on cross-sectional
imaging studies performed for reasons unrelated to adrenal
disease [1]. The increasing use of radiologic investigations
including abdominal ultrasound, computed tomography (CT),
and magnetic resonance imaging (MRI) has led to an increase
in the detection of such incidental adrenal lesions. The
prevalence of AIs is approximately 2% on autopsies and
http://dx.doi.org/10.1016/j.euf.2015.12.006
2405-4569/# 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
as 5% in those aged 70 yr) [2]. More recent large
contemporary imaging series reported the incidence of AIs
to be as high as 45% in patients without prior history of
malignancy [3].
The majority of incidentally detected adrenal lesions are
benign and nonfunctional (nonsecreting) adrenal adeno-
mas. Table 1 summarizes the differential diagnosis associ-
ated with AIs. There is remarkable variation in the reported
risk of adrenocortical carcinoma in AIs. In patients with no
prior history of malignancy, it is less likely for incidental
224 EUROPEAN UROLOGY FOCUS 1 (2016) 223230

Table 1 Common differential diagnosis and summary of initial hormonal/screening evaluation of adrenal incidental masses

Differential diagnosis Biochemical abnormality Primary screening test Other conrmatory tests Circumstances leading to
false positives

Adrenal adenoma Nonfunctional Unenhanced CT <10-HU See algorithm (Fig. 1) Lipid poor adrenal adenomas
attenuation, <4 cm
Cushings syndrome Hypercortisolism Low-dose (1 mg) overnight Serum cortisol, 24-h urinary Anticonvulsants, exogenous
(secondary to excessive dexamethasone test: failure to free cortisol,* late-night glucocorticoid use
production by the adrenal suppress endogenous cortisol: salivary cortisol*
gland) >1.8 mg/dl
Pheochromocytoma Hypercatecholaminemia 24-h urinary fractionated Metaiodobenzylguanidine Stop acetaminophen 5 d prior
metanephrines or plasma free scintigraphy to urinary catecholamine
metanephrines testing; stop tricyclic
antidepressants,
phenoxybenzamine
Primary Elevated plasma Rule out and correct 1. Normal saline infusion test Stop potassium-sparing
hyperaldosteronism aldosterone hypokalemia; ratio of morning 2. Oral sodium loading test diuretics, mineralocorticoid
concentration and serum aldosterone (ng/dl) to 3. Fludrocortisone receptor blockers/
suppressed plasma renin renin activity (ng/ml/h) >20 and suppression test spironolactone, beta blockers
activity serum aldosterone >15 ng/ml 4. Captopril suppression test 6 wk prior to screening
Adrenocortical Functional (as above) or CT/MRI: incidentaloma (4 or See algorithm (Fig. 1)
carcinoma nonfunctional <4 cm)
Metastatic disease Biopsy, PET-CT

CT = computed tomography; HU = Hounseld units; PET = positron emission tomography.

*
Repeat testing recommended.

adrenal masses to harbor malignant disease. In one of the
largest published series of AIs detected on CT imaging
involving 1049 patients with no prior history of cancer, no
malignant lesions were reported [3]. However, in patients
with oncologic disease, adrenal metastases may occur in
approximately 50% of incidentally detected adrenal masses
[2]. Other reports that included surgical series estimated the
risk of adrenocortical carcinoma to be approximately 2% in
AIs <4 cm and 25% in AIs >6 cm [4].
This nonstructured review outlines the initial metabolic
and radiologic work-up required for the accurate diagnosis
of an AI and the evidence supporting recommendations for
managing such patients conservatively or with surgical
resection. With the increasing use of minimally invasive
surgery, we reviewed the evidence comparing minimally
invasive and open surgery for patients undergoing adrenal-
ectomy for AIs. Last, we reviewed recommendations for
appropriate follow-up for patients on surveillance.
2. Evidence acquisition
such lesions are benign or malignant and metabolically
active/functional or nonfunctional. The National Institutes
of Health (NIH) consensus statement recommends meta-
bolic work-up for all incidentally diagnosed adrenal masses,
as >10% of such lesions are potentially functional [6]. De-
spite the 2002 NIH guidelines, in clinical practice, up to 80%
of patients are inappropriately underinvestigated and do
not receive recommended endocrinology referral [7].
Starting with history and physical examination, symp-
toms and signs of adrenal hyperfunction and malignancy
should be elucidated, followed by metabolic evaluation and
radiologic imaging. The most frequent forms of adrenal
hypersecretion include hormones derived from the adrenal
cortex (cortisol, aldosterone, or androgens) or the adrenal
medulla (catecholamines) [8]. In general, all newly diag-
nosed AIs should be tested for cortisol and catecholamine
hypersecretion and, occasionally, androgens. Furthermore,
hypertensive or hypokalemic patients should also have
plasma aldosterone concentration and plasma renin activity
measurement.

A literature search of English-language publications that 3.1.1. Cushings syndrome

included the keywords adrenal incidentaloma and incidental
adrenal mass was performed through July 2015 using
PubMed. Relevant original articles and guidelines on the
management of the incidental adrenal mass were ultimate-
ly selected for analysis, with the consensus of all authors.
3. Evidence synthesis
3.1. Metabolic evaluation of the incidental adrenal mass
Although several guidelines exist, to date, there is no
prospective validation of the suggested investigation of AIs
[4,5]. The ultimate goals in evaluation are to determine if
Cushings syndrome, also known as hypercortisolism, is a
constellation of signs and symptoms associated with
excessive glucocorticosteroid activity. These signs and
symptoms are mostly nonspecific, but some are more
suggestive of Cushings syndrome. These patients often
have classic features related to the effects of glucocorti-
costeroids on adipose tissue and musculoskeletal tissues
(rounding of the face with plethora [moon facies],
dorsocervical and supraclavicular fat pads, central obesity
with thinning of the extremities, proximal muscle weak-
ness, easy bruising, acne, and purple striae). New-onset
hypertension or worsening blood pressure control can be
observed in these patients. On laboratory testing, these
patients may have hyperglycemia, hypokalemia, alkalosis,
 EUROPEAN UROLOGY FOCUS 1 (2016) 223230
and leukocytosis (with increased percentage of neutrophils,
lymphopenia, and eosinopenia).
Cushings syndrome is often caused by exogenous use of
glucocorticosteroids, and a minority of patients have
endogenous cortisol production. Patients with endogenous
Cushings syndrome can be divided into adrenocorticotro-
pic hormone (ACTH)dependent Cushings syndrome
(ACTH-producing pituitary adenoma, ectopic ACTH produc-
tion, and rarely ectopic corticotropin-releasing hormone
production) or ACTH-independent Cushings syndrome
associated with adrenal tumors. In these patients with
overt cortisol overproduction, ACTH is usually very low or
near the lower end of normal reference range (usually <10
pg/ml), with evidence of hypercortisolism (elevated 24-h
urinary free cortisol, elevated late-night salivary cortisol, or
failure of 1 mg overnight dexamethasone suppression test).
Some patients with AIs have no typical features to suggest
Cushings syndrome, but they have subtle laboratory
abnormities to point to a mild case of autonomous cortisol
production. The term subclinical Cushings syndrome (SCS)
was first introduced in 1981 to describe patients with AIs
and autonomously producing glucocorticoids with no
obvious signs of overt Cushings syndrome [9]. SCS can be
seen in 58% patients with AIs [10]. Despite the term
subclinical, these patients are still are at risk due to
continuous excess cortisol exposure, including hyperten-
sion, diabetes mellitus, osteoporosis, and obesity. As the
majority of patients do not have overt Cushings syndrome,
24-h urinary cortisol levels are often normal and are not
sufficient for diagnosis. Autonomous cortisol hypersecre-
tion is best assessed initially with an overnight dexameth-
asone (1 mg) suppression test. A patients failure to
suppress cortisol levels (<1.8 mg/dl) following low-dose
dexamethasone administration (1 mg overnight dexameth-
asone suppression test) is indicative of Cushings syndrome
and has sensitivity >90%. If positive, further confirmatory
tests are required to rule out a false-positive rate of
approximately 10% [11]. Other tests include the late-night
salivary cortisol test and ACTH measurement [12].
Because adrenocortical carcinoma can present with
mixed cortisol and adrenal androgen overproduction,
careful assessment is warranted to exclude adrenocortical
carcinoma. Most cortisol-producing adrenal adenomas are
associated with excessive cortisol and low adrenal andro-
gens (dehydroepiandrosterone sulfate).
3.1.2. Pheochromocytoma
Approximately 5% of all AIs are pheochromocytomas, and
up to 50% of these may be clinically silent (ie, normoten-
sive), hence biochemical assessment is warranted for all
patients. First-line investigations for pheochromocytomas
should include either plasma free metanephrine/normeta-
nephrine or 24-h urine fractionated metanephrines [13]. By
itself, testing for plasma free metanephrine is associated
with lower specificity (8590%) [14], especially in older
patients, and has higher false-positive rates if patients are
taking acetaminophen, tricyclic antidepressants, or phe-
noxybenzamine; therefore, these medications should be
withheld 5 d prior to testing [15]. Two reviews recently
225
addressed the topics of pheochromocytoma and metaboli-
cally active urologic tumors and included details on optimal
perioperative management strategies [16,17].
3.1.3. Primary aldosteronism
Approximately 1% of AIs are aldosterone-hypersecreting
tumors that clinically present as Conns syndrome, in which
patients may present with hypertension. Nearly 5% of
patients with new-onset hypertension may have an
underlying adrenal mass [18]. Consequently, routing
screening for hyperaldosteronism is mainly recommended
in hypertensive patients. Historically, low serum potassium
levels were the first-line investigation for aldosterone
hypersecretion; however, up to 40% of patients exhibit
normal or low serum potassium [19]. The more appropriate
first-line screening for Conns syndrome is the ratio of
morning plasma aldosterone to renin, for which a ratio of
>20 and a concurrent elevated serum aldosterone level
(>15 ng/ml) are suggestive of primary hyperaldosteronism
and must be followed by confirmatory tests (eg, 24-h
urinary aldosterone level while on a high salt diet or 4-h
normal saline suppression test with plasma aldosterone
measurement) (Table 1).
3.2. Imaging and size of adrenal mass
AIs are most commonly found on abdominal ultrasound, CT,
or MRI, with an incidence of approximately 5%. The latter
two imaging modalities form the cornerstones for further
characterization and evaluation for such adrenal masses. A
homogenous mass with smooth borders and attenuation of
<10 Hounsfield units (HU) on unenhanced CT is strongly
suggestive of a lipid-rich benign adrenal adenoma. The low
attenuation on unenhanced CT corresponds to high
intracytoplasmic lipid content. Overall, 98% of adrenal
lesions with 10 HU on noncontrast CT are benign adrenal
adenomas; however, attenuation alone is not diagnostic
because 1530% of adrenal adenomas are lipid poor, with
10 HU on noncontrast CT, and thus may be interpreted as
malignant [20,21]. In such cases, additional imaging with
intravenous contrast is required. On delayed contrast-
enhanced CT, adrenal adenomas exhibit rapid washout of
the intravenous contrast medium. If the absolute washout
of contrast is 50% after 10 min or relative washout is 40%
after 15 min from administration, this is indicative of
adenoma, with sensitivity and specificity of 100% [22,23].
Similarly, MRI can assess the differences in signal between
fat and water to evaluate intracellular lipid content. This is
known as chemical shift MRI, which exploits different
resonant frequency rates of protons in fat and water. Adrenal
adenomas exhibit loss of signal intensity on out-of-phase
sequences compared with in-phase imaging, confirming the
presence of intra-adrenal fat. In comparison to CT, however,
contrast-enhanced MRI with gadolinium washout studies
does not appear to exhibit the same diagnostic strength as its
CT counterpart. Consequently, CT washout studies remain
the gold standard, especially in the evaluation of lipid-poor
adenomas [21,24]. Moreover, patients with a previous
history of extra-adrenal malignancy should also undergo
226 EUROPEAN UROLOGY FOCUS 1 (2016) 223230
positron emission tomographyCT with flurodeoxyglucose
(FDG) and/or biopsy to rule out metastasis. In general,
metastatic lesions tend to have increased FDG uptake
because of increased glucose metabolism, whereas benign
adenomas do not [25].
The use of functional imaging such as iodine 131 metaio-
dobenzylguanidine (MIBG) imaging for the diagnosis for
pheochromocytomas is limited, given that most pheochro-
mocytomas can be accurately diagnosed with cross-
sectional imaging and metabolic evaluation for catechola-
mines; however, this modality can be useful for detection of
metastatic disease. MIGB is a structural analog of norepi-
nephrine, and increased uptake of MIGB suggests the
presence of chromaffin cells found in tumors such as
pheochromocytomas. Previous series suggest sensitivities
and specificities of 100% and 94%, respectively, in identify-
ing pheochromocytomas with MIGB imaging [26].
Regardless of the initial imaging modality used for
diagnosis of an adrenal mass, size of the mass is one of the
most important parameters that helps distinguish malig-
nant and nonmalignant adrenal lesions, in which larger
masses are more likely to exhibit adverse clinical and
pathologic features. In a large Italian multi-institutional
retrospective analysis of 887 patients with AIs, tumor
diameter was highly correlated with the risk of malignancy.
Adrenal masses with tumor diameter >4 cm were associat-
ed with 90% sensitivity in adrenal cortical carcinoma (ACC)
detection [27].
Another review of >1300 patients with AIs showed that
the incidence of malignant neoplasms significantly in-
creased for masses >6 cm in diameter and should be
considered malignant until proven otherwise, almost
always requiring definitive resection [10]. Similarly, in-
creasing size is associated with increasing incidence of
adrenal hypersecretion [28]. Consequently, almost all
nonfunctioning lesions <4 cm are benign and may be
observed in the absence of worrisome radiologic features or
clinical suspicion for malignancy based on history. In
contrast, the optimal diagnosis for adrenal masses between
4 and 6 cm is not established and remains controversial. If
such lesions are hormonally inactive and exhibit benign
radiologic appearance, they also may be considered for
observation [8].
Occasionally bilateral adrenal masses are noted, and
these should be interpreted and investigated in the context
of the whole clinical picture, as they could be related to a
neoplastic (malignant or benign), infectious, or immune
process [29].
3.3. The role of biopsy
Histologically, adrenal adenomas cannot always be reliably
differentiated from ACC on fine needle aspiration (FNA) or
biopsy [20]. FNA and biopsies are usually reserved for
patients with known extra-adrenal malignancies when
histologic diagnosis will assist in distinguishing between
adrenal versus nonadrenal origin of the lesion. Furthermore,
biopsy should be considered only after pheochromocytoma
has been ruled out, when radiologic investigation has
reached its limit, and results of biopsy will ultimately
change or influence clinical management. A recent study by
Villeli et al. [30] reported specificity of 88%, sensitivity of
86%, positive predictive value of 97%, and a much lower
negative predictive value of 58% for diagnoses using adrenal
core biopsy specimens.
Image-guided FNA or biopsy is safe overall, and
complication rates are low (<3%) [31]. When indicated,
FNA or biopsy should always be carried out after
biochemical investigation has excluded pheochromocyto-
mas, which have been reported to lead to life-threatening
hypertensive crisis [8]. Other complications include adre-
nal/abdominal hematoma, infection, pneumothorax, pan-
creatitis, tumor seeding along the needle track, and
hemorrhage [31,32].
3.4. Indications for surgery and patient selection
Indications for surgery for AIs should consider factors that
involve both tumor functionality and radiologic criteria that
may suggest malignancy. History and physical examination
of patients at presentation will highlight signs and
symptoms that reflect glucocorticoid, mineralocorticoid,
adrenal sex hormone, or catecholamine excess. If present,
these must be confirmed with further biochemical inves-
tigations, as outlined (Fig. 1). Surgery should be considered
in all patients with functional adrenal cortical tumors.
Similarly, all patients with biochemical evidence of
pheochromocytomas should undergo adrenal resection.
More than 60% of incidentalomas <4 cm are benign
adenomas. Of these, <2% represent ACC and are almost
always benign lesions if nonfunctional. In contrast, if the
adrenal mass is >6 cm, ACC accounts for >25% cases, of
which only 15% are benign adenomas [8]. For lesions 4
6 cm, closer follow-up or surgery should be considered,
taking into account other imaging parameters including
attenuation >10 HU, irregular boarders, or inconclusive
percentage of contrast-enhanced washout on CT or MRI.
Rapid growth rate in adrenal masses has also been
advocated as a potential indicator of malignancy, even
though a reliable adrenal mass growth cutoff value is not
well established to confirm or exclude a malignant lesion
[33]. Furthermore, almost all lesions resected due to
increased growth kinetics are benign. In a prospective
multi-institutional Swedish study, 29 of 229 patients
(12.6%) undergoing surveillance of AIs underwent resection
due to an increase in size of adrenal lesions ranging between
5 and 10 mm, all exhibiting benign pathology. Another
study reviewing 873 patients with AIs showed that up to 9%
of lesions grew at least 1 cm at mean follow-up of 3 yr, with
only one lesion proving malignant. The authors concluded
that the rate of malignant transformation is approximately
1 in 1000 [10]. Although such reports suggest that growth
kinetics in conservatively managed adrenal lesions corre-
late poorly with malignancy rates, growth rates of 1 cm
often prompt surgical resection; therefore, change in
adrenal mass size should be used in conjunction with other
imaging and clinical characteristics when surgical resection
is being considered.
 EUROPEAN UROLOGY FOCUS 1 (2016) 223230 227

Incidental Adrenal Mass (>1 cm) diagnosed on CT/MRI

Hormonal evaluation in all patients
1. Dexamethasone (1 mg) suppression test
2. Plasma or 24-h urine metanephrines
3. If hypertensive, include plasma aldosterone:renin ratio

Functional Mass Nonfunctional Mass

(Hormonal evaluation abnormal/positive) (Hormonal evaluation normal/negative)

Size of adrenal mass <4 cm Size of adrenal mass 4 cm

Endocrinology Consultation
Confirmation testing of autonomous
secretion of cortisol, catecholamines,
aldosterone, other Benign Imaging Features Suspicious Imaging Features
Medical and preoperative management Homogenous Heterogeneous
Low density Necrosis
Smooth margins Irregular margins
Unenhanced CT 10-HU attenuation Unenhanced CT >10-HU attenuation

Consider surgery
CT with contrast

50% contrast washout <50% contrast washout

at 10 min at 10 min

Positive autonomous hormonal secretion Consider Conservative Management Consider Surgery

Growth >1 cm Repeat imaging 612 mo If history of malignancy: PET-CT, biopsy
Size of mass 4 cm Repeat hormonal evaluation annually for 4 yr

Fig. 1 Algorithm for management of an adrenal incidentaloma.

CT = computed tomography; HU = Hounsfield units; MRI = magnetic resonance imaging; PET = positron emission tomography.

Metastases are common in patients with an adrenal mass
and a history of malignancy. Work-up of these masses
should always exclude the possibility of other adrenal
tumors, with proper imaging, serologic testing, and
sometimes biopsy. Adrenalectomy can be a viable treat-
ment option for well-selected patients with adrenal
metastases. In general, operative intervention is best
reserved for patients in whom the adrenal gland is the
solitary site or in the presence of oligometastatic disease for
which complete resection is feasible. The absence of local
invasion into contiguous structures and a disease-free
interval >6 mo from the original cancer diagnosis are also
suggestive of favorable tumor biology and better survival
outcomes after adrenalectomy [34].
Historically, open adrenalectomy (OA) was considered
the standard of care for surgical excision of the majority of
adrenal tumors; however, contemporary studies show that
minimally invasive laparoscopic adrenalectomy (LA), done
with a transperitoneal or retroperitoneal approach, can be
offered safely to carefully selected patients. Relative
contraindications for LA continue to include tumor size,
obesity, and ACC; however, the increasing use of minimally
invasive surgery in adrenalectomy reflects the increasing
skill sets of surgeons that attain oncologic outcomes similar
to open surgery while offering improved postoperative pain
levels, decreased morbidity, less or equivalent operative
blood loss, shorter hospital stay, and faster recovery [35].
Despite the obvious advantages of LA, the underlying
adrenal pathology is paramount in planning the optimal
surgical approach, as it may significantly affect oncologic
and survival outcomes for the patient if complete resection
is compromised. Most important, cancer control, especially
in ACC, is highly dependent on wide local excision with
negative margins and meticulous attention to prevent
tumor spillage in these friable tumors. ACC tends to be an
aggressive disease in which locoregional recurrence can be
as high as 60% [36]. Consequently, known adrenal vein or
vena caval involvement are still regarded as absolute
contraindications to laparoscopic surgery. Furthermore, to
obtain an R0 resection of a locally advanced ACC, it is often
mandatory to resect adjacent organs such as the wall of the
vena cava, liver, spleen, colon, pancreas, and/or stomach,
mandating an OA approach [37,38].
The Society of American Gastrointestinal and Endoscopic
Surgeons guidelines for the minimally invasive treatment of
adrenal pathology state that large adrenal tumors without
pre- or intraoperative evidence of primary ACC can be
approached by LA by a skilled laparoscopic surgeon;
however, such cases may be associated with longer
operating room time, more blood loss, and a higher rate
of conversion to open surgery. If any evidence for metastatic
carcinoma is found intraoperatively, conversion to an open
approach is warranted and should be strongly considered
[35]. Of great concern is that previous studies have shown
228 EUROPEAN UROLOGY FOCUS 1 (2016) 223230
significant differences in recurrence-free and overall
survival favoring OA compared with LA in patients with
ACC, with significantly higher rates of peritoneal carcino-
matosis within the LA group, strongly supporting the
oncologic benefits of OA in ACC [39].
The advent of robotic surgery has rapidly increased in
popularity worldwide, including robotic adrenalectomy
(RA), which was first described in 2001 [40]. Brunaud et al.
reported that RA might be especially useful for patients with
high body mass index (BMI; >30) and for large tumors
(>5.5 cm) [41,42]. Nevertheless, in a recent systematic
review and meta-analysis comparing LA and RA, patients
undergoing RA had lower BMI, highlighting a significant
selection bias for RA. Furthermore, RA was shown to have no
significant difference in operative time or complication rate
compared with LA [43]. In the same meta-analysis, although
RA had less hospitalization (0.5 d less) and blood loss
(25 ml) compared with LA, these differences were not
clinically significant. Given the increased cost of RA
compared with LA [41] and the lack of clear patient
outcomes with RA, further high-quality evidence is needed
before firm recommendations can be provided. Other
minimally invasive technical modifications of minimally
invasive adrenalectomy include laparoendoscopic single-
site surgery and minilaparoscopy.
3.5. Follow-up for the incidental adrenal mass
There is currently no national or international consensus for
the follow-up of AIs. The 2003 NIH statement for follow-up
for nonresected adrenal masses recommends repeat CT in 6
12 mo. For lesions that do not increase in size, further
radiologic evaluation is not supported within the literature. A
summary of 21 studies involving >1690 patients with
median follow-up ranging from 2 to 7 yr attributed the risk
of developing malignancy, hyperfunction, or overt disease to
be very low at 0.05%, 1.2%, and 0.9%, respectively. Similarly, in
the same review, of the 212 of 1690 lesions (12.5%) that
increased in size, only 1 was observed to be malignant [44].
Furthermore, Cawood and colleagues highlighted that
during follow-up, false-positive rates of recommended
investigations may be 50 times greater than true-positive
rates [45]. The average CT scan for follow-up exposes each
patient to 23 mSv of ionizing radiation, which equates to a
1 in 4302170 chance of causing fatal cancer; this is similar
to the chance of developing adrenal malignancy during the
3-yr follow-up of AI [45].
With regard to abnormal adrenal hypersecretion of
glucocorticoids and catecholamines, the observation that
autonomous function not present at baseline may be
subsequently detected at follow-up testing has led to the
recommendation of repeating hormonal testing annually
for at least 4 yr [4648]. The rationale for annual screening
is that development of subtle hypercortisolism may have
detrimental effects on cardiovascular risk profile and bone
health [2]. In one study, the overall risk of developing
additional endocrine abnormalities was 47% at 5 yr. When
participants were divided by mass size at diagnosis, the risk
of further endocrine changes in the first 2 yr of follow-up
was higher in patients with adrenal lesions >3 versus <3 cm
[46]. It is important to note in the same study, however, that
of the 82% patients that had hormonal irregularities noted at
initial diagnosis, none went on to develop subclinical or overt
Cushings syndrome on follow-up.
In conclusion, standardized follow-up protocols or
guidelines are controversial, and evidence to date suggests
that small radiographically benign lesions (<4 cm) that are
functionally inactive do not require further (or require less
frequent) investigation. Outside of these parameters, even
though radiologic and hormonal follow-up is recom-
mended, the yield and cost-effectiveness of such testing
is unknown [1,49].
4. Conclusions
AIs are becoming more common due to increased use of body
imaging. Ideally, management of patients with AIs should
involve a multidisciplinary approach with surgeons, radi-
ologists, and endocrinologists to determine whether such
lesions are benign or malignant and functional or nonfunc-
tional and/or whether they require surgical resection.
Author contributions: Jose A. Karam had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
Study concept and design: Thomas, Karam.
Acquisition of data: Thomas, Blute, Seitz, Habra, Karam.
Analysis and interpretation of data: Thomas, Blute, Seitz, Habra, Karam.
Drafting of the manuscript: Thomas, Karam.
Critical revision of the manuscript for important intellectual content:
Thomas, Blute, Seitz, Habra, Karam.
Statistical analysis: None.
Obtaining funding: None.
Administrative, technical, or material support: Karam.
Supervision: Karam.
Other (specify): None.
Financial disclosures: Jose A. Karam certies that all conicts of interest,
including specic nancial interests and relationships and afliations
relevant to the subject matter or materials discussed in the manuscript
(eg, employment/afliation, grants or funding, consultancies, honoraria,
stock ownership or options, expert testimony, royalties, or patents led,
received, or pending), are the following: None.
Funding/Support and role of the sponsor: None.
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