• There are myriad causes (see Differential Diagnosis).
• Decreased synthesis or release of thyroid hormone can result from thyroid gland dysfunction (primary hypothyroidism) or from pituitary/hypothalamic dysfunction leading to under-stimulation of the thyroid gland (secondary and tertiary hypothyroidism).

• A genetic predisposition exists in patients with chronic lymphocytic thyroiditis (CLT), the most common cause of acquired thyroiditis in non-endemic areas; 30% to 40% of patients have a familial history of thyroid disease, and up to 50% of their first-degree relatives have thyroid antibodies.
• Associations of CLT with certain HLA haplotypes are weak and not consistently reproducible.
• Autoimmune thyroid disease may be part of Schmidt syndrome (type II polyglandular autoimmune disease), which also involves Addison disease and type 1 diabetes mellitus. This incompletely penetrant autosomal dominant disorder demonstrates stronger HLA linkage.
• Genetic syndromes associated with higher incidence of autoimmune thyroiditis:
  • Down syndrome
  • Turner syndrome (especially those with isochromosome Xq)

• May develop at any age.
• CLT prevalence correlates with iodine intake, such that countries as the United States and Japan with the highest dietary iodine also have the highest CLT prevalence.

• The most significant complication during childhood is impaired linear growth.
• Myxedema coma may occur.

• Chronic lymphocytic thyroiditis (often referred to as Hashimoto thyroiditis)
• Autoimmune polyendocrine syndrome (Schmidt syndrome)

• Post-viral subacute thyroiditis
• Associated with congenital infections
  • Rubella
  • Toxoplasmosis

• Goitrogen ingestion
  • Iodides
  • Expectorants
  • Thioureas

• Following surgical thyroidectomy for thyroid cancer, hyperthyroidism, or extensive neck tumors.
• Following radioiodine ablative therapy for hyperthyroidism or thyroid cancer.
• Following irradiation to the head or neck for cancer treatment.
• Medications: lithium, amiodarone, iodine contrast dyes.

• Cystinosis
• Histiocytosis X

• “Late-onset” congenital-large ectopic gland

• Down syndrome
• Turner syndrome

• Hypothalamic or pituitary disease

Question: Growth pattern?
Significance: Linear growth failure can be the first sign of thyroid dysfunction

Question: Declining school performance?
Significance: Sensitive marker for lethargy and reduced focusing

Question: Any symptoms of hypothyroidism and their duration?
Significance: Early primary hypothyroidism can be asymptomatic. The presence of hypothyroid-related symptoms indicates progression from compensated to uncompensated hypothyroidism.

Question: Notice any thyroid gland enlargement? Its duration? Tenderness?
Significance: Goiter may be the presenting sign of acquired hypothyroidism. Tenderness suggests an infectious process.

Question: Any past medical history factors associated with hypothyroidism? (e.g., genetic syndromes, radiation exposure, medications, history of diabetes)
Significance: Any of these factors should raise the concern for possible acquired hypothyroidism.

Question: Familial history of thyroid disease (hyper or hypo) or other autoimmune endocrinopathies
Significance: Family history of thyroid disease or other autoimmune endocrinopathies increases the risk of developing autoimmune thyroid disease.

Finding: Bradycardia
Significance: Thyroid hormone has cardiac effects.

Finding: Short stature (or fall-off on growth curve), and increased upper:lower segment ratio
Significance: Euthyroidism is required to maintain normal growth.

Finding: Goiter: note consistency, symmetry, nodularity, signs of inflammation
Significance: Goiter characteristics may give a clue regarding the cause of the hypothyroidism and provide a clinical manner to follow during therapy.

Finding: Myxedema (water retention)
Significance: Myxedema is not limited to the subcutaneous tissue. It may also lead to cardiac failure, pleural effusions, and coma.

Finding: Muscle hypertrophy, yet muscle weakness most obvious in arms, legs, and tongue.
Significance: Hypothyroidism causes disordered muscle function.

Finding: Delayed relaxation phase of deep tendon reflexes
Significance: Due to slowed muscle contraction, not a change in the transmission rate of the nervous impulse.

Finding: Pale, cool, dry, carotenemic skin
Significance: (due to decreased cell turnover)

Finding: Increase in lanugo hair
Significance: Can be seen in children with hypothyroidism and revised with treatment.

Test: T4 (low) and TSH (elevated)
Significance: Elevated TSH with normal T4 represents a state of compensated primary hypothyroidism.

Test: Free T4
Significance: The most sensitive marker for secondary/tertiary hypothyroidism (in which case, TSH elevation is lost and total T4 may still be in the low end of the normal range).

Test: Antithyroglobulin and antimicrosomal (antiperoxidase) antibodies
Significance: Markers for CLT.

Test: Head MRI
Significance: Suspected secondary/tertiary hypothyroidism; pituitary or hypothalamic lesion

The following conditions may test false-positive for acquired hypothyroidism:

Test: Thyroid-binding globulin deficiency
Significance: Low total T4, but normal free T4 and TSH

Test: Peripheral resistance to thyroid hormone
Significance: Normal/high total T4

Test: “Euthyroid sick” syndrome
Significance: Low T4 and T3; normal/low TSH; increased shunting to reverse T3

• Indicated for the treatment of overt or compensated hypothyroidism.
• 2 to 5 µg/kg/d po, once daily
• Monitor T4 and TSH and titrate dose to maintain normalized TFTs.
• Duration of therapy
  • Lifetime
  • 30% of children with CLT will undergo spontaneous remission, and reassessment of need for treatment can be done after growth is completed.

• Whenever starting medication or adjusting dose, check T4 and TSH 4 to 6 weeks later, to assess adequacy of the new dose.

• Treated patients often resume growth at a rate greater than normal (catch-up growth).
• Other signs and symptoms resolve at a variable rate.
• Goiters in CLT may not completely regress with treatment (enlargement due to persistent inflammation does not correct, though TSH-mediated hypertrophy will).

• Monitor response to treatment by measuring T4 and TSH levels to ensure compliance.

• If patients are compliant, prognosis is excellent.
• In children in whom treatment has been delayed, catch-up growth may not fully normalize height to predicted values.

Q: What happens if my child forgets a dose?
A: Give the dose as soon as you remember. If it is the next day, give two doses.

Q: How long will my child have to take these pills?
A: Probably for life.

Q: Are there any side effects from the medication?
A: No. The medication contains only the hormone that your child’s thyroid gland is not making. The hormone is made synthetically, so there is also no infectious risk.

Q: If my child takes twice the dose, will his or her growth catch up faster?
A: Your child may grow a little faster but will also have adverse effects from having too much thyroid hormone.

Q: Does the medication have to be taken at any particular time of day?
A: No, but consistently choosing the same time of day helps to remember taking it.

Betterle C, Volpato M, Greggio AN, Presotto F. Type 2 polyglandular autoimmune disease (Schmidt syndrome). J Pediatr Endocrinol Metab 1996;(9 Suppl 1):113–123.

Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med 1996;335:99–107.

LaFranchi S. Thyroiditis and acquired hypothyroidism. Pediatr Ann 1992;21(1):29–39.

Rickees SA, Bode HH, Crawford JD. Long-term growth in juvenile acquired hypothyroidism: The failure to achieve normal adult stature. N Engl J Med 1988;318:599–602.