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Approach to goiter in children

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Mohit Kehar

INTRODUCTION thyroiditis.1 More often following careful investigation no

A goiter is an enlargement of the thyroid gland. Persons underlying cause can be identified for diffuse euthyroid
with enlarged thyroids may have normal function of the enlargement often termed as simple colloid goiter. Table 2
gland (euthyroidism), thyroid deficiency (hypothyroid- gives the causes of thyroid enlargement.
ism), or overproduction of the hormones (hyperthyroid-
ism). Table 1: Thyroid volume according to age
Clinically goiter is defined as enlargement of the lobes greater
Age (years) Volume (ml) mean ± SD
than the terminal phalanx of the patient’s thumb.
7 3.1 ± 1.3
WHO Classification/Grading 8 3.3 ± 1.2
• 0: No goiter 9 3.6 ± 1.3
• 1a: Palpable lobe 10 4.0 ± 1.5
• 1b: Noticeable gland on neck hyperextension 11 4.9 ± 1.5
• 2: Gland noticeable with neck in normal position
12 5.3 ± 1.4
• 3: Visible gland at a distance of 10 m.
There have been various reports which showed the dis- 13 6.1 ± 1.6
crepancy of palpation and USG assessment in evaluation 14 6.3 ± 1.5
of goiter, palpation is relatively inaccurate for assessing
the prevalence of goiter in mild iodine deficiency, thyroid
volume measurement by ultrasound in children provides Table 2: Differential diagnosis
a useful tool for the assessment of goiter in mild iodine • Autoimmune thyroid disease
deficiency. Chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis)
Formula for thyroid volume (formula of a rotation Graves’ disease
• Colloid (simple) goiter
ellipsoid model): width × length × thickness × 0.52 for
• Goitrogen exposure and drugs like lithium, etc.
each lobe. Table 1 gives the size of thyroid at various ages.
• Dyshormonogenesis
• Infectious
Differential Diagnosis of Goiter Subacute (viral) thyroiditis
The enlargement of the thyroid is generally mediated by Chronic suppurative thyroiditis
an increase in the pituitary-derived thyroid stimulating • Anatomic abnormalities
hormone (TSH) or in antibodies that bind to the TSH Thyroglossal duct cyst
receptor, such as the thyroid stimulating immunoglobu- Hemiagenesis of the thyroid
lin’s (TSIs) found in Graves’ disease. Inflammation or • Nodular goiter
infiltration may cause diffuse, symmetrical enlargement, Solitary nodule (adenoma, carcinoma, cyst)
although the gland is usually asymmetric and nodular.  Multinodular goiter secondary to autoimmune thyroid
The most common inflammatory process is autoimmune disease
 Approach to Goiter in Children
Clinical and Investigative Evaluation of
Patient with Goiter
While evaluating a patient of goiter we should ask for fam-
ily history of thyroid disease, consanguinity, geographi-
cal area of residence, exposure to irradiance, medication
history, goitrogens, and in newborns history of maternal
exposure to iodine or antithyroid drugs, symptoms sug-
gestive of hyperthyroid or hypothyroid.
While examining a patient, general physical examina-
tion should be done, including vitals. We should look for
features/signs suggestive of hypo/hyperthyroidism. The
neck is then examined and thyroid is examined for nodu-
larity, consistency, surface, and texture, signs of compres-
sion, lymphadenopathy, and bruits. A symmetric, diffuse
enlarged gland needs an evaluation for hyperthyroidism
and primary hypothyroidism. One should look for the
scars, asymmetry and any neck swelling. Erythema overly-
ing a tender swelling may be due to suppurative thyroiditis
or infected thyroglossal cyst or brachial cleft cyst. Goiter
due to dyshormonogenesis varies in size and tends to be
softer in consistency with or without bruits. Disturbance
in thyroid function and multinodularity usually excludes
malignancy as opposed to a firm, irregular, painless single
nodule.
In determining the cause of thyromegaly (Flow
chart 1) the initial diagnostic evaluation should be lim-
ited to measurements of TSH and thyroid antibodies. The
T4 level is required only if the TSH level is elevated. Free
T4 measurement is preferred to the total T4 level because
the former is not influenced by thyroid binding globulin
levels and, therefore, better reflects the active thyroid hor-
mone level. Thyroid antibody titers greater than 1:2000 or
10 mIU/L most likely indicate autoimmune thyroiditis.2,3
Flow chart 1: Most common causes of a goiter − negative (-ve); positive (+ve); thyroid antibodies (TAB);
thyroid stimulating hormone (TSH)
1255
Lower levels may simply reflect a nonspecific inflamma-
tion of the thyroid gland. Imaging is only required if a
solitary nodule is suspected.
Goiter and Hypothyroidism
The most common cause of acquired hypothyroidism is
chronic lymphocytic thyroiditis. Chronic lymphocytic thy-
roiditis (CLT), also known as Hashimoto’s thyroiditis is
uncommon in children younger than four years of age.
The peak age of onset in the first-two decades of life is in
early to midpuberty. The ratio is 2:1 in favor of females
versus males; this ratio is less skewed than in adulthood
when 90 percent of cases occur in females. Although there
is no defined pattern of inheritance, a family history is
reported in 30 percent of affected children. It is well estab-
lished that the risk of CLT is higher in individuals with
chromosomal abnormalities such as Turner syndrome,
Klinefelter syndrome and Down syndrome. There is also
an increase in association with other autoimmune diseases.
The prevalence of thyroid autoantibodies in children and
adolescents with type 1 diabetes has been reported to be as
high as 20 to 40 percent, while abnormal thyroid function
is reported in approximately 7 percent of these patients.
Autoimmune thyroid disease may be associated with
a euthyroid state, hypothyroidism or hyperthyroidism. In
the early stages, when examined the gland will be smooth
and soft, progressing to a granular or pebbly texture, and
then becoming firm and irregular. It has been seen that
most children are euthyroid at diagnosis. Hypothyroidism
will be present in 3 to 13 percent of patients, and they
will show typical symptoms, 3 to 35 percent of patients
have elevated TSH concentrations and normal T4 levels, a
state termed subclinical or compensated hypothyroidism.
1256 Section 8: Endocrinology
Rarely, children may present with transient thyrotoxicosis
with suppressed TSH, and elevated serum T3 and T4 lev-
els, a condition known as toxic thyroiditis or hashitoxico-
sis.
An endemic goiter is the most common preventable
cause of mental retardation. However, because of the rou-
tine addition of iodine to salt in the western world, it is
not seen in that area. Goitrogen exposure should be con-
sidered in patients with a goitre and negative thyroid anti-
bodies, and it will generally be evident from the patient’s
history. In addition to prescribed medications, it is impor-
tant to ask about the use of over-the-counter preparations,
such as iodide-containing expectorants and natural rem-
edies. Dyshormonogenesis usually presents as congenital
hypothyroidism, however, milder forms may present later
as acquired hypothyroidism with goitre and negative thy-
roid antibodies. A family history should be sought because
this is an autosomal recessive condition. While hypothy-
roidism may also occur if a patient has hypothalamic and
pituitary lesions (i.e. tertiary and secondary hypothyroid-
ism, respectively), a goitre is not a clinical feature of these
cases.
Symptoms of Hypothyroidism
Deceleration of growth, goiter, which may be a presenting
feature, typically is non tender and firm, with a rubbery
consistency and a pebbly surface. Myxedematous changes
of the skin, there will be constipation, cold intolerance,
an increased need for sleep develop insidiously. Osseous
maturation is delayed, adolescents typically have delayed
puberty, whereas younger children may present with
galactorrhea or pseudoprecocious puberty.
Treatment
The decision to treat with l-thyroxine is clear for overt
hypothyroidism, but controversial for a euthyroid goiter
or compensated hypothyroidism. In overt hypothyroid
patients levothyroxine given orally is the treatment of
choice, newborn require 10 μg/kg/24 hours and children
with hypothyroidism require about 4 μg/kg/24 hours, and
adults require only 2 μg/kg/24 hours.
For patients who are compensated the approach used
is to monitor patients with mild elevations of TSH level
(less than 10 mIU/L) six months after the diagnosis is con-
firmed and then annually. Repeat levels of TSH are often
normal. In those patients with a confirmed TSH level that
is greater than 10 mIU/L, treatment with thyroxine is usu-
ally continued until growth is complete. Thyroid status is
then reassessed to determine the need for ongoing treat-
ment. Patients with a TSH that is greater than 20 mIU/L
have a high rate of progression to hypothyroidism, and
are treated with thyroxine.4
SIMPLE GOITER (COLLOID GOITER)
The most common causes of euthyroid goiter in childhood
are CLT and a colloid goiter. Thyroid enlargement that is
not caused by inflammatory, infectious or neoplastic causes
is termed a colloid goiter, also. Histological findings seen
in cases of colloid goiter include enlarged thyroid follicles
filled with abundant colloid. The cause remains contro-
versial. Although TSH is the principal growth-stimulating
factor for the thyroid, TSH levels are normal in patients
with colloid goiter. The condition predominates in girls
and has a peak incidence before and during the pubertal
years. The goiter may be small or large. It is firm in half
the patients and occasionally is asymmetric or nodular.
Levels of TSH are normal or low, scintiscans are normal,
and thyroid antibodies are absent. The natural history is
for spontaneous reduction with time, and treatment with
thyroxine is not indicated.
GOITER AND HYPERTHYROIDISM
Hyperthyroidism results from excessive secretion of thy-
roid hormone and during childhood is mainly due to
Graves’ disease. Other causes are rare and should be sus-
pected only when there is an atypical presentation.5 As
seen with other thyroid disorders females are predomi-
nantly affected and the ratio of affected females versus
males is less pronounced than in adulthood. A family his-
tory of autoimmune thyroid disease is commonly present.
Other rare causes of hyperthyroidism that have been
observed in children include toxic uninodular goiter
(Plummer disease), hyperfunctioning thyroid carcinoma,
thyrotoxicosis factitia, subacute thyroiditis, and acute sup-
purative thyroiditis. In infants who are born to mothers
with Graves' disease, hyperthyroidism is almost always a
transitory phenomenon; classic Graves' disease during the
neonatal period is usually rare.
Graves' disease is an autoimmune disorder in which
there is production of thyroid-stimulating immunoglobu-
lin (TSI) which results in diffuse toxic goiter. About 5 per-
cent of all patients with hyperthyroidism are younger than
15 years of age and the peak incidence in these children
occurs during adolescence.
Manifestations of Hyperthyroidism
Symptoms include nervousness, irritability, heat intoler-
ance, excessive sweating, palpitations, fatigue and weak-
ness, weight loss with increased appetite, frequent bowel
movements, and oligomenorrhea. Patients are anxious,
restless, and fidgety. Skin is warm and moist, and finger-
nails may separate from the nailbed (Plummer’s nails).
Eyelid retraction and lid lag may be present. Cardiovas-
cular findings include tachycardia, systolic hypertension,
systolic murmur, and atrial fibrillation. A fine tremor,
 Approach to Goiter in Children
hyperreflexia, and proximal muscle weakness may also be
present. Long-standing thyrotoxicosis may lead to osteo-
penia. In Graves’ disease, the thyroid is usually diffusely
enlarged to two to three times its normal size, and a bruit
or thrill may be present. Infiltrative ophthalmopathy (with
variable degrees of proptosis, periorbital swelling, and
ophthalmoplegia) and dermopathy (pretibial myxedema)
may also be found. In subacute thyroiditis, the thyroid is
exquisitely tender and enlarged with referred pain to the
jaw or ear, and sometimes accompanied by fever and pre-
ceded by an upper respiratory tract infection.
Evaluation
The diagnosis of Graves’ disease is made by finding a
suppressed TSH level with elevated T4 and/or T3 levels.
When the patient’s clinical presentation is mild, free T4
levels may be high normal, with an inappropriately sup-
pressed TSH, in which case T3 levels should be measured.
Antithyroglobulin antibodies and thyroid peroxidase anti-
body levels may be positive but they are not pathogenic.
TSI, if measured, will be positive.
Hashitoxicosis can present similar to Graves disease.
However, hashitoxicosis is a self-limiting condition and
lacks ophthalmopathy. It is caused by autoimmune dam-
age to follicular cells, resulting in the release of preformed
T4 and T3 into circulation. Transient or permanent hypo-
thyroidism may follow a period of hyperthyroidism. If the
hyperthyroidism lasts more than a few weeks, the diagno-
sis of hashitoxicosis is usually unlikely.
Subacute thyroiditis is generally caused by viral infec-
tions and is generally not seen in pediatric age group.
Children with subacute thyroiditis have an enlarged, ten-
der thyroid, malaise, fatigue and weakness that develop
after an upper respiratory tract infection. There are two
distinct phases in the progression. During the acute stage
(two to six weeks), preformed T4 and T3 are released from
the inflamed thyroid follicles, resulting in hyperthyroid-
ism with or without clinical symptoms. For the next two
to seven months, the damaged thyroid is less effective at
synthesizing hormone, resulting in low to normal T3 and
T4 concentrations with a compensatory elevation of TSH.
Nearly all patients recover from hypothyroidism.
Autonomously hyperfunctioning adenomas secrete T3
and cause mild hyperthyroidism. The thyroid is usually of
small or normal size with a palpable nodule. Symptoms
of hyperthyroidism generally occur when the nodule is
greater than 2.5 cm in diameter. The nodules are rarely
malignant, and surgery is curative in such cases.
Treatment
Most centers recommend initial medical therapy using
antithyroid drugs rather than radioiodine or subtotal
1257
thyroidectomy, although radioiodine is gaining accept-
ance as initial treatment in children >10 years of age.
The 2 antithyroid drugs in widest use are propylthioura-
cil (PTU) and methimazole, the initial dosage of PTU is
5 to 10 mg/kg/24 hours given 3 times daily, and that of
methimazole is 0.25 to 1.0 mg/kg/24 hours given once or
twice daily. A b-adrenergic blocking agent like proprano-
lol (0.5–2.0 mg/kg/24 hours po, given 3 times daily) sup-
plemented to antithyroid drugs in the management of
severely toxic patients. Surgery or radioiodine treatment
is indicated when adequate cooperation for medical man-
agement is not possible, when adequate trial of medical
management has failed to result in permanent remission,
or when severe side effects preclude further use of ant
thyroid drugs. The eye changes remit gradually; severe
ophthalmopathy may require treatment with high-dose
prednisone, orbital radiotherapy, or orbital decompres-
sion surgery.
NODULAR GOITER
Thyroid nodules are relatively common in adolescents
these nodules are usually asymptomatic and often discov-
ered incidentally, but they raise the fear of cancer. A multi-
nodular goiter is almost invariably caused by Hashimoto's
thyroiditis and it carries a good prognosis. The asymp-
tomatic, solitary thyroid nodule is a thyroid adenoma,
thyroid carcinoma or a thyroid cyst. Thyroid carcinoma
occurs in approximately one per one million persons/year
in the first-two decades of life.6
A large-sized nodule (more than 4 cm) which is rap-
idly growing has a hard texture with fixation to adjacent
structures, associated with regional lymphadenopathy and
hoarseness or dysphagia are suspicious clinical features,
increasing the probability of malignancy.
Investigation of a solitary nodule should begin with
thyroid function tests and thyroid antibodies. Thyroid
cancer is unlikely in the presence of hypothyroidism,
hyperthyroidism or autoimmune thyroiditis.7 The first
line investigation is thyroid ultrasound. It will identify
other cervical masses that can be confused with a thyroid
nodule, such as a thyroglossal duct cyst, and determine
whether the nodule is cystic, solid or mixed. If a purely
cystic thyroid nodule is identified, no further investiga-
tions are required and the patient may be followed con-
servatively. If, however, the lesion is solid or of mixed
density, then radionuclide scanning (99mTc-pertechnetate,
123
I or131I) is indicated to differentiate a hyperfunction-
ing (hot) from a hypofunctioning (cold) nodule. A hyper-
functioning nodule is, most likely, a benign hyperfunc-
tioning adenoma. A cold nodule in a pediatric patient has
a more likelihood of malignancy than in adults with cold
nodule.
 1258 Section 8: Endocrinology
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1. Lafranchi S. Thyroiditis and acquired hypothyroidism. Pedi-
atr Ann 1992;21:29-39.
2. Weetman AP. Autoimmune thyroiditis: Predisposition and
pathogenesis. Clin Endocrinol 1992;36:307-23.6.
3. Beever K, Bradbury J, Phillips D, et al. Highly sensitive
assays of autoantibodies to thyroglobulin and to thyroid per-
oxidase. Clin Chem 1989;35:1949-54.
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4. Sarah Muirhead. Diagnostic approach to goitre in children
Paediatr Child Health 2001 April; 6(4):195-9.
5. Foley TP. Jr. Thyrotoxicosis in childhood. Pediatr
Ann 1992;21:43-6.
6. Foley TP. Disorders of the thyroid in children. In: Sperling
MA, (Eds). Pediatric Endocrinology. 1st edn. Philadelphia:
WB Saunders Company; 1996.pp171-94.
7. LaFranchi S. Adolescent thyroid disorders. Adolesc Med
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