16.2 Thyroid & Adrenal Disorders

Congenital Hypothyroidism

Congenital hypothyroidism (CH) is the most common preventable cause of intellectual disability worldwide, with an incidence of roughly 1 in 2,000-4,000 live births — rates run higher in populations with elevated rates of parental consanguinity, which is directly relevant across much of the Arab Board's candidate region.

Etiology:

• Thyroid dysgenesis (agenesis, ectopic/lingual thyroid, hypoplasia) — the most common cause overall, usually sporadic
• Dyshormonogenesis — an inherited defect in thyroid hormone synthesis, typically autosomal recessive, more frequent where consanguinity is common
• Central (hypothalamic/pituitary) hypothyroidism — rare, may signal panhypopituitarism
• Transient forms — from maternal antithyroid drugs, or iodine deficiency/excess

Newborn screening: essentially all national programs screen with a heel-prick blood spot measuring TSH (or T4 with reflex TSH) at 24-72 hours of life — timing balances avoiding the physiologic neonatal TSH surge against not missing an early case. An elevated screening TSH triggers confirmatory serum free T4 and TSH testing.

Presentation if missed: most affected newborns look clinically normal at birth because maternal T4 crosses the placenta and provides partial protection. Left untreated, features emerge over weeks: prolonged jaundice (unconjugated hyperbilirubinemia), poor feeding, lethargy, hypotonia, hoarse cry, macroglossia, umbilical hernia, a wide-open posterior fontanelle, constipation, and cold, mottled skin. This is precisely why universal screening exists — by the time clinical signs appear, the window for normal neurodevelopment has already started closing.

Treatment urgency: this is a true emergency for the developing brain, even though the infant looks well. Levothyroxine (10-15 mcg/kg/day) should start as soon as the diagnosis is confirmed — ideally within the first 2 weeks of life — with the goal of normalizing free T4 within 2 weeks and TSH within about a month. The earlier treatment starts, the better the neurodevelopmental outcome; delay correlates directly with lower IQ.

Acquired Hypothyroidism / Hashimoto Thyroiditis

Hashimoto thyroiditis (chronic lymphocytic, or autoimmune, thyroiditis) is the most common cause of acquired hypothyroidism in iodine-sufficient children and adolescents. It is autoimmune, driven by anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies, more common in girls, and clusters with other autoimmune conditions — type 1 diabetes, celiac disease, Down syndrome, and Turner syndrome are classic associations worth memorizing for the exam.

Presentation is often subtle: growth deceleration (a declining height velocity is frequently the earliest and most reliable clue in children, in contrast to adults where weight change dominates), fatigue, cold intolerance, constipation, dry skin, and a firm, non-tender, sometimes lobulated goiter. Pubertal timing is usually delayed, though severe longstanding untreated hypothyroidism can rarely cause precocious puberty with galactorrhea (Van Wyk-Grumbach syndrome) — a classic exam trap worth flagging.

Treatment and monitoring: levothyroxine is dosed by weight and titrated to keep free T4 in the upper-normal range with a normalized TSH. After starting or adjusting the dose, recheck TSH and free T4 in about 4-6 weeks, then every 6-12 months once stable. Unlike congenital hypothyroidism, missing the diagnosis for a few months in an older child rarely causes permanent cognitive injury — the treatment urgency is highest in infancy, when the brain is still undergoing rapid thyroid-hormone-dependent development; this contrast in urgency is itself a useful way to keep the two conditions straight on the exam.

Graves Disease (Hyperthyroidism)

Graves disease is the most common cause of hyperthyroidism in children and adolescents. Like Hashimoto thyroiditis, it is autoimmune, but here TSH-receptor stimulating antibodies (TRAb/TSI) activate the thyroid rather than destroying it, producing excess T4 and T3 with a suppressed TSH.

Presentation contrasts sharply with hypothyroidism: weight loss despite increased appetite, heat intolerance, tremor, anxiety, tachycardia (or new-onset atrial arrhythmia in adolescents), proximal muscle weakness, and a diffuse, often bruiting goiter. Exophthalmos and pretibial myxedema occur less often in children than in adults but remain classic associations. Growth may accelerate initially, but prolonged excess thyroid hormone can advance bone age and compromise final adult height.

Diagnosis: suppressed TSH with elevated free T4 (and often T3); positive TRAb/TSI confirms Graves in most cases. A thyroid uptake scan showing diffuse increased uptake helps distinguish Graves from subacute thyroiditis (low uptake) or an autonomously functioning nodule.

Treatment: methimazole (an antithyroid drug) is first-line in children, titrated to normalize free T4 while keeping TSH suppressed early in therapy. Propranolol controls adrenergic symptoms (tachycardia, tremor) while thyroid hormone levels fall. Definitive therapy with radioactive iodine or thyroidectomy is reserved for relapse, poor adherence, or specific clinical scenarios — not first-line in most pediatric cases. Thyroid storm (fever, delirium, cardiovascular collapse in severe hyperthyroidism) is rare but life-threatening; treat with high-dose antithyroid drugs, beta-blockade, iodine (given after antithyroid drug loading), and supportive ICU care.

Exam contrast: Hashimoto causes a firm goiter with growth deceleration and positive anti-TPO antibodies; Graves causes a hyperdynamic picture with weight loss, tachycardia, and suppressed TSH with stimulating receptor antibodies.

Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders of adrenal steroidogenesis. 21-hydroxylase deficiency (CYP21A2 gene) accounts for approximately 90-95% of all CAH cases and is the form tested most heavily. Because it is autosomal recessive, incidence rises where consanguineous marriage is common — again directly relevant to the Arab Board population.

Pathophysiology: 21-hydroxylase normally converts precursors toward cortisol and aldosterone. Its deficiency blocks both pathways, so precursors are shunted into androgen synthesis, producing cortisol +/- aldosterone deficiency together with androgen excess.

Salt-wasting crisis: typically presents in the first 1-2 weeks of life with vomiting, poor feeding, dehydration, hyponatremia, hyperkalemia, hypoglycemia, and shock — a true adrenal crisis if unrecognized.

Ambiguous genitalia: in affected girls (46,XX), in-utero androgen excess virilizes the external genitalia — clitoromegaly and labial fusion — while the internal reproductive organs remain normal female (ovaries and uterus intact), because anti-Müllerian hormone is never produced. This combination — virilized external genitalia with normal internal female organs — is a classic exam identifier. Affected boys (46,XY) typically look phenotypically normal at birth, sometimes with subtle genital hyperpigmentation, so a salt-wasting crisis in the second week of life may be their first clue — a key trap, since normal-appearing genitalia can falsely reassure.

Diagnosis: markedly elevated 17-hydroxyprogesterone (17-OHP), the precursor that accumulates just before the enzymatic block; many national programs include CAH in newborn screening.

Treatment: hydrocortisone to replace cortisol and suppress excess ACTH-driven androgen production; fludrocortisone plus sodium supplementation for salt-wasting forms; stress-dose glucocorticoids during illness, fever, or surgery to prevent an adrenal crisis.

Non-classic CAH is a separate, milder allelic variant of 21-hydroxylase deficiency that does not cause salt-wasting or genital ambiguity at birth. It typically presents later — with premature pubarche, hirsutism, acne, or menstrual irregularity in a child or adolescent — and is diagnosed by a baseline or ACTH-stimulated 17-OHP that is elevated but well below classic-range values. Distinguishing it from classic CAH matters clinically: non-classic disease usually needs only low-dose glucocorticoid therapy for symptom control, not routine mineralocorticoid replacement or stress dosing for salt-wasting risk.