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Approach to goiter in children

Chapter · January 2012

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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 1255

Clinical and Investigative Evaluation of Lower levels may simply reflect a nonspecific inflamma-
Patient with Goiter tion of the thyroid gland. Imaging is only required if a
While evaluating a patient of goiter we should ask for fam- solitary nodule is suspected.
ily history of thyroid disease, consanguinity, geographi-
cal area of residence, exposure to irradiance, medication Goiter and Hypothyroidism
history, goitrogens, and in newborns history of maternal The most common cause of acquired hypothyroidism is
exposure to iodine or antithyroid drugs, symptoms sug- chronic lymphocytic thyroiditis. Chronic lymphocytic thy-
gestive of hyperthyroid or hypothyroid. roiditis (CLT), also known as Hashimoto’s thyroiditis is
While examining a patient, general physical examina- uncommon in children younger than four years of age.
tion should be done, including vitals. We should look for The peak age of onset in the first-two decades of life is in
features/signs suggestive of hypo/hyperthyroidism. The early to midpuberty. The ratio is 2:1 in favor of females
neck is then examined and thyroid is examined for nodu- versus males; this ratio is less skewed than in adulthood
larity, consistency, surface, and texture, signs of compres- when 90 percent of cases occur in females. Although there
sion, lymphadenopathy, and bruits. A symmetric, diffuse is no defined pattern of inheritance, a family history is
enlarged gland needs an evaluation for hyperthyroidism reported in 30 percent of affected children. It is well estab-
and primary hypothyroidism. One should look for the lished that the risk of CLT is higher in individuals with
scars, asymmetry and any neck swelling. Erythema overly- chromosomal abnormalities such as Turner syndrome,
ing a tender swelling may be due to suppurative thyroiditis Klinefelter syndrome and Down syndrome. There is also
or infected thyroglossal cyst or brachial cleft cyst. Goiter an increase in association with other autoimmune diseases.
due to dyshormonogenesis varies in size and tends to be The prevalence of thyroid autoantibodies in children and
softer in consistency with or without bruits. Disturbance adolescents with type 1 diabetes has been reported to be as
in thyroid function and multinodularity usually excludes high as 20 to 40 percent, while abnormal thyroid function
malignancy as opposed to a firm, irregular, painless single is reported in approximately 7 percent of these patients.
nodule. Autoimmune thyroid disease may be associated with
In determining the cause of thyromegaly (Flow a euthyroid state, hypothyroidism or hyperthyroidism. In
chart 1) the initial diagnostic evaluation should be lim- the early stages, when examined the gland will be smooth
ited to measurements of TSH and thyroid antibodies. The and soft, progressing to a granular or pebbly texture, and
T4 level is required only if the TSH level is elevated. Free then becoming firm and irregular. It has been seen that
T4 measurement is preferred to the total T4 level because most children are euthyroid at diagnosis. Hypothyroidism
the former is not influenced by thyroid binding globulin will be present in 3 to 13 percent of patients, and they
levels and, therefore, better reflects the active thyroid hor- will show typical symptoms, 3 to 35 percent of patients
mone level. Thyroid antibody titers greater than 1:2000 or have elevated TSH concentrations and normal T4 levels, a
10 mIU/L most likely indicate autoimmune thyroiditis.2,3 state termed subclinical or compensated hypothyroidism.

Flow chart 1: Most common causes of a goiter − negative (-ve); positive (+ve); thyroid antibodies (TAB);
thyroid stimulating hormone (TSH)
1256 Section 8: Endocrinology

Rarely, children may present with transient thyrotoxicosis SIMPLE GOITER (COLLOID GOITER)
with suppressed TSH, and elevated serum T3 and T4 lev- The most common causes of euthyroid goiter in childhood
els, a condition known as toxic thyroiditis or hashitoxico- are CLT and a colloid goiter. Thyroid enlargement that is
sis. not caused by inflammatory, infectious or neoplastic causes
An endemic goiter is the most common preventable is termed a colloid goiter, also. Histological findings seen
cause of mental retardation. However, because of the rou- in cases of colloid goiter include enlarged thyroid follicles
tine addition of iodine to salt in the western world, it is filled with abundant colloid. The cause remains contro-
not seen in that area. Goitrogen exposure should be con- versial. Although TSH is the principal growth-stimulating
sidered in patients with a goitre and negative thyroid anti- factor for the thyroid, TSH levels are normal in patients
bodies, and it will generally be evident from the patient’s with colloid goiter. The condition predominates in girls
history. In addition to prescribed medications, it is impor- and has a peak incidence before and during the pubertal
tant to ask about the use of over-the-counter preparations, years. The goiter may be small or large. It is firm in half
such as iodide-containing expectorants and natural rem- the patients and occasionally is asymmetric or nodular.
edies. Dyshormonogenesis usually presents as congenital Levels of TSH are normal or low, scintiscans are normal,
hypothyroidism, however, milder forms may present later and thyroid antibodies are absent. The natural history is
as acquired hypothyroidism with goitre and negative thy- for spontaneous reduction with time, and treatment with
roid antibodies. A family history should be sought because thyroxine is not indicated.
this is an autosomal recessive condition. While hypothy-
roidism may also occur if a patient has hypothalamic and
GOITER AND HYPERTHYROIDISM
pituitary lesions (i.e. tertiary and secondary hypothyroid-
ism, respectively), a goitre is not a clinical feature of these Hyperthyroidism results from excessive secretion of thy-
cases. roid hormone and during childhood is mainly due to
Graves’ disease. Other causes are rare and should be sus-
Symptoms of Hypothyroidism pected only when there is an atypical presentation.5 As
seen with other thyroid disorders females are predomi-
Deceleration of growth, goiter, which may be a presenting nantly affected and the ratio of affected females versus
feature, typically is non tender and firm, with a rubbery males is less pronounced than in adulthood. A family his-
consistency and a pebbly surface. Myxedematous changes tory of autoimmune thyroid disease is commonly present.
of the skin, there will be constipation, cold intolerance, Other rare causes of hyperthyroidism that have been
an increased need for sleep develop insidiously. Osseous observed in children include toxic uninodular goiter
maturation is delayed, adolescents typically have delayed (Plummer disease), hyperfunctioning thyroid carcinoma,
puberty, whereas younger children may present with thyrotoxicosis factitia, subacute thyroiditis, and acute sup-
galactorrhea or pseudoprecocious puberty. purative thyroiditis. In infants who are born to mothers
with Graves' disease, hyperthyroidism is almost always a
Treatment transitory phenomenon; classic Graves' disease during the
neonatal period is usually rare.
The decision to treat with l-thyroxine is clear for overt
Graves' disease is an autoimmune disorder in which
hypothyroidism, but controversial for a euthyroid goiter
there is production of thyroid-stimulating immunoglobu-
or compensated hypothyroidism. In overt hypothyroid
lin (TSI) which results in diffuse toxic goiter. About 5 per-
patients levothyroxine given orally is the treatment of
cent of all patients with hyperthyroidism are younger than
choice, newborn require 10 μg/kg/24 hours and children
15 years of age and the peak incidence in these children
with hypothyroidism require about 4 μg/kg/24 hours, and
occurs during adolescence.
adults require only 2 μg/kg/24 hours.
For patients who are compensated the approach used
Manifestations of Hyperthyroidism
is to monitor patients with mild elevations of TSH level
(less than 10 mIU/L) six months after the diagnosis is con- Symptoms include nervousness, irritability, heat intoler-
firmed and then annually. Repeat levels of TSH are often ance, excessive sweating, palpitations, fatigue and weak-
normal. In those patients with a confirmed TSH level that ness, weight loss with increased appetite, frequent bowel
is greater than 10 mIU/L, treatment with thyroxine is usu- movements, and oligomenorrhea. Patients are anxious,
ally continued until growth is complete. Thyroid status is restless, and fidgety. Skin is warm and moist, and finger-
then reassessed to determine the need for ongoing treat- nails may separate from the nailbed (Plummer’s nails).
ment. Patients with a TSH that is greater than 20 mIU/L Eyelid retraction and lid lag may be present. Cardiovas-
have a high rate of progression to hypothyroidism, and cular findings include tachycardia, systolic hypertension,
are treated with thyroxine.4 systolic murmur, and atrial fibrillation. A fine tremor,
Approach to Goiter in Children 1257

hyperreflexia, and proximal muscle weakness may also be thyroidectomy, although radioiodine is gaining accept-
present. Long-standing thyrotoxicosis may lead to osteo- ance as initial treatment in children >10 years of age.
penia. In Graves’ disease, the thyroid is usually diffusely The 2 antithyroid drugs in widest use are propylthioura-
enlarged to two to three times its normal size, and a bruit cil (PTU) and methimazole, the initial dosage of PTU is
or thrill may be present. Infiltrative ophthalmopathy (with 5 to 10 mg/kg/24 hours given 3 times daily, and that of
variable degrees of proptosis, periorbital swelling, and methimazole is 0.25 to 1.0 mg/kg/24 hours given once or
ophthalmoplegia) and dermopathy (pretibial myxedema) twice daily. A b-adrenergic blocking agent like proprano-
may also be found. In subacute thyroiditis, the thyroid is lol (0.5–2.0 mg/kg/24 hours po, given 3 times daily) sup-
exquisitely tender and enlarged with referred pain to the plemented to antithyroid drugs in the management of
jaw or ear, and sometimes accompanied by fever and pre- severely toxic patients. Surgery or radioiodine treatment
ceded by an upper respiratory tract infection. is indicated when adequate cooperation for medical man-
agement is not possible, when adequate trial of medical
Evaluation management has failed to result in permanent remission,
The diagnosis of Graves’ disease is made by finding a or when severe side effects preclude further use of ant
suppressed TSH level with elevated T4 and/or T3 levels. thyroid drugs. The eye changes remit gradually; severe
When the patient’s clinical presentation is mild, free T4 ophthalmopathy may require treatment with high-dose
levels may be high normal, with an inappropriately sup- prednisone, orbital radiotherapy, or orbital decompres-
pressed TSH, in which case T3 levels should be measured. sion surgery.
Antithyroglobulin antibodies and thyroid peroxidase anti-
body levels may be positive but they are not pathogenic. NODULAR GOITER
TSI, if measured, will be positive. Thyroid nodules are relatively common in adolescents
Hashitoxicosis can present similar to Graves disease. these nodules are usually asymptomatic and often discov-
However, hashitoxicosis is a self-limiting condition and ered incidentally, but they raise the fear of cancer. A multi-
lacks ophthalmopathy. It is caused by autoimmune dam- nodular goiter is almost invariably caused by Hashimoto's
age to follicular cells, resulting in the release of preformed thyroiditis and it carries a good prognosis. The asymp-
T4 and T3 into circulation. Transient or permanent hypo- tomatic, solitary thyroid nodule is a thyroid adenoma,
thyroidism may follow a period of hyperthyroidism. If the thyroid carcinoma or a thyroid cyst. Thyroid carcinoma
hyperthyroidism lasts more than a few weeks, the diagno- occurs in approximately one per one million persons/year
sis of hashitoxicosis is usually unlikely. in the first-two decades of life.6
Subacute thyroiditis is generally caused by viral infec- A large-sized nodule (more than 4 cm) which is rap-
tions and is generally not seen in pediatric age group. idly growing has a hard texture with fixation to adjacent
Children with subacute thyroiditis have an enlarged, ten- structures, associated with regional lymphadenopathy and
der thyroid, malaise, fatigue and weakness that develop hoarseness or dysphagia are suspicious clinical features,
after an upper respiratory tract infection. There are two increasing the probability of malignancy.
distinct phases in the progression. During the acute stage Investigation of a solitary nodule should begin with
(two to six weeks), preformed T4 and T3 are released from thyroid function tests and thyroid antibodies. Thyroid
the inflamed thyroid follicles, resulting in hyperthyroid- cancer is unlikely in the presence of hypothyroidism,
ism with or without clinical symptoms. For the next two hyperthyroidism or autoimmune thyroiditis.7 The first
to seven months, the damaged thyroid is less effective at line investigation is thyroid ultrasound. It will identify
synthesizing hormone, resulting in low to normal T3 and other cervical masses that can be confused with a thyroid
T4 concentrations with a compensatory elevation of TSH. nodule, such as a thyroglossal duct cyst, and determine
Nearly all patients recover from hypothyroidism. whether the nodule is cystic, solid or mixed. If a purely
Autonomously hyperfunctioning adenomas secrete T3 cystic thyroid nodule is identified, no further investiga-
and cause mild hyperthyroidism. The thyroid is usually of tions are required and the patient may be followed con-
small or normal size with a palpable nodule. Symptoms servatively. If, however, the lesion is solid or of mixed
of hyperthyroidism generally occur when the nodule is density, then radionuclide scanning (99mTc-pertechnetate,
greater than 2.5 cm in diameter. The nodules are rarely 123
I or131I) is indicated to differentiate a hyperfunction-
malignant, and surgery is curative in such cases. ing (hot) from a hypofunctioning (cold) nodule. A hyper-
functioning nodule is, most likely, a benign hyperfunc-
Treatment tioning adenoma. A cold nodule in a pediatric patient has
Most centers recommend initial medical therapy using a more likelihood of malignancy than in adults with cold
antithyroid drugs rather than radioiodine or subtotal nodule.
1258 Section 8: Endocrinology

REFERENCEs 4. Sarah Muirhead. Diagnostic approach to goitre in children


Paediatr Child Health 2001 April; 6(4):195-9.
1. Lafranchi S. Thyroiditis and acquired hypothyroidism. Pedi- 5. Foley TP. Jr. Thyrotoxicosis in childhood. Pediatr
atr Ann 1992;21:29-39. Ann 1992;21:43-6.
2. Weetman AP. Autoimmune thyroiditis: Predisposition and 6. Foley TP. Disorders of the thyroid in children. In: Sperling
pathogenesis. Clin Endocrinol 1992;36:307-23.6. MA, (Eds). Pediatric Endocrinology. 1st edn. Philadelphia:
3. Beever K, Bradbury J, Phillips D, et al. Highly sensitive WB Saunders Company; 1996.pp171-94.
assays of autoantibodies to thyroglobulin and to thyroid per- 7. LaFranchi S. Adolescent thyroid disorders. Adolesc Med
oxidase. Clin Chem 1989;35:1949-54. 1994;5:65-86.

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