Thyroid Gland in Pediatrics — Comprehensive Note Set (Chapter 34)

Fetal development of the thyroid

• As early as the 10th week of gestation, the fetal thyroid begins synthesizing thyroid hormone

  • Thyroid hormone appears in fetal serum by week 11 and increases throughout gestation

• Fetal pituitary–thyroid axis largely functions independently of the maternal pituitary–thyroid axis

  • Maternal TSH cannot cross the placenta

  • Maternal thyroid hormone can cross the placenta in limited amounts

• At birth, there is a TSH surge

  • Peaks at about $70~ ext{mU/L}$ within 30 minutes

  • TH levels rise rapidly during the first days of life in response to this TSH surge

  • TSH decreases to childhood levels within a few weeks

• Physiologic neonatal TSH surge can yield a false‑positive newborn screen for hypothyroidism

  • Blood sampled on the first day of life may show high TSH, prompting concern for congenital hypothyroidism

Physiology

• Hypothalamic TRH stimulates the anterior pituitary to release TSH

• TSH stimulates the thyroid to synthesize and release $T4$ and $T3$ via negative feedback involving the hypothalamus, pituitary, and thyroid

• T4 is the predominant thyroid hormone secreted by the thyroid gland

• Most circulating $T3$ and $T4$ are bound to thyroxine‑binding globulin (TBG), albumin, and prealbumin; less than 1 ext{%} are in the free form

• $T4$ is deiodinated in tissues to $T3$, which binds to nuclear thyroid hormone receptors and exerts biologic effects by modifying gene expression

• Causes of low $T4$ include: hypothyroidism (central or primary), prematurity, malnutrition, and severe illness

• Total $T4$ is low in conditions that decrease TBG (e.g., familial TBG deficiency, cirrhosis, renal failure) and in patients receiving glucocorticoids or androgens; TSH and FT4 often remain in the normal range

• Conversely, total $T3$ and $T4$ may be elevated in conditions with increased TBG (congenital TBG excess, pregnancy, estrogen therapy); clinically euthyroid

• A $T3$ resin uptake (T3RU) helps differentiate between binding protein problems and true hypo‑ or hyperthyroidism

Hypothyroidism (congenital & acquired)

• Essentials of diagnosis & typical features

  • Growth impairment, decreased physical activity, weight gain, constipation, dry skin, cold intolerance, and delayed puberty

  • Untreated congenital hypothyroidism: thick tongue, large fontanels, poor muscle tone, hoarseness, umbilical hernia, jaundice, and intellectual impairment

  • $T4$, FT4, and $T3$ resin uptake are low; TSH is elevated in primary hypothyroidism

• General considerations

  • Thyroid hormone deficiency may be congenital or acquired

  • Can be due to defects in the thyroid (primary) or in the hypothalamus/pituitary (central)

Causes of hypothyroidism (Table 34‑4)

• A. Congenital

  • Aplasia, hypoplasia, or maldescent of the thyroid

  • Inborn errors of thyroid hormone synthesis, secretion, or recycling

  • Maternal antibody‑mediated inhibition of TSH binding to its receptor

  • TSH receptor defect

  • Thyroid hormone receptor defect

  • In utero exposures: radioiodine therapy, goitrogens (e.g., propylthiouracil, methimazole), iodine excess

  • Iodide deficiency

• B. Acquired (juvenile hypothyroidism)

  • Autoimmune (lymphocytic) thyroiditis

  • Thyroidectomy or radioiodine therapy

  • Irradiation to the thyroid

  • Thyrotropin (TSH) deficiency

  • TRH deficiency due to hypothalamic injury or disease

  • Medications: iodides (excess such as amiodarone; deficiency), lithium, cobalt

  • Large hemangiomas

  • Idiopathic

• Congenital hypothyroidism occurs in about $1{:}3000{-}1{:}4000$ infants

• Untreated congenital hypothyroidism causes severe neurocognitive impairment

• Most cases are sporadic from hypoplasia/aplasia or failure of migration (e.g., lingual/sub‑lingual thyroid)

• Severe maternal iodine deficiency results in fetal and maternal $T4$ deficiency with irreversible fetal brain damage

• Acquired hypothyroidism in childhood is often due to chronic lymphocytic (Hashimoto) thyroiditis

Clinical Findings in hypothyroidism

• A. Symptoms and signs

  • Newborns: most appear normal even when thyroid is absent; thyroid testing is included in newborn screening due to intellectual impairment risk; jaundice may be present

  • Juvenile hypothyroidism: poor linear growth; delayed bone age and dental eruption; dry, thick, scaly, coarse, pale, cool, or sallow skin; dry or brittle hair; lateral thinning of eyebrows; hypotonia; slow relaxation of deep tendon reflexes; physical and mental slowing; nonpitting myxedema; constipation; cold intolerance; bradycardia; delayed puberty; occasional pseudopuberty (due to weak FSH activity with markedly elevated TSH)

  • In enzymatic defects or autoimmune Hashimoto thyroiditis, the thyroid gland may be enlarged; inchildren with Hashimoto, enlargement is usually symmetrical, moderately firm, and not nodular; Hashimoto thyroiditis may have a cobblestone thyroid surface

• B. Laboratory findings

  • Primary hypothyroidism: total $T4$ and FT4 may be normal or decreased; serum $TSH$ elevated

  • Circulating autoantibodies to thyroid peroxidase and/or thyroglobulin may be present

  • Central hypothyroidism: $TSH$ is low or inappropriately normal with low $T4/FT4$; may be associated with other pituitary/hypothalamic deficiencies

• C. Imaging

  • Thyroid imaging helps establish cause but does not affect treatment; not strictly necessary

  • Bone age is delayed; cardiomegaly is common

• D. Screening programs for neonatal hypothyroidism

  • All newborns should be screened shortly after birth; screening measures total $T4$ or $TSH$ depending on state

  • Abnormal newborn screening should be confirmed with venous $T4$ and $TSH$; treatment should start as soon as possible

• Treatment

  • Synthetic $T4$ (levothyroxine) at $75{-}100 ext{ mcg}/ ext{m}^2/ ext{day}$ is the drug of choice for hypothyroidism

  • In neonates with congenital hypothyroidism, initial dose is $10{-}15 ext{ mcg}/ ext{kg}/ ext{day}$

  • Serum total $T4$ or FT4 concentrations monitor initial adequacy because neonatal TSH may remain elevated for weeks

  • Subsequently, monitor $T4$ and $TSH$ in combination