Residency · Residency · Pediatrics

Thyroid Disorders in Children

Introduction

Thyroid disorders are among the most common endocrine conditions in pediatrics. Congenital hypothyroidism is the most frequent preventable cause of intellectual disability, detected through newborn screening. Acquired hypothyroidism, most often from Hashimoto thyroiditis, and hyperthyroidism from Graves disease each present unique diagnostic and management challenges in children. Early recognition and treatment are critical for preserving neurodevelopment, growth, and metabolic health.

Thyroid Physiology

The hypothalamic-pituitary-thyroid axis regulates thyroid hormone production: TRH from the hypothalamus stimulates TSH from the anterior pituitary, which stimulates T4 and T3 production. T4 (thyroxine) is the predominant circulating hormone and is converted to the active form T3 (triiodothyronine) peripherally by deiodinases. Thyroid hormones are essential for brain development (myelination, synaptogenesis), linear growth, thermogenesis, and metabolic regulation. The fetal thyroid begins producing hormones by 12 weeks gestation, and maternal T4 crosses the placenta and is critical for early fetal brain development.

Congenital Hypothyroidism

Epidemiology and Etiology

The incidence is approximately 1 in 2,000-4,000 live births. Thyroid dysgenesis (ectopic, hypoplastic, or absent thyroid) accounts for 80-85% of cases. Dyshormonogenesis (defects in thyroid hormone synthesis) accounts for 10-15%. Central (secondary or tertiary) congenital hypothyroidism is rare and may be missed by screening programs that measure only TSH.

Newborn Screening

Universal newborn screening detects elevated TSH (primary screening in most programs) or low T4 (some programs). Confirmatory testing with serum TSH and free T4 should be done within 24-48 hours of an abnormal screen. Thyroid ultrasound assesses thyroid anatomy, and thyroid scintigraphy (I-123 or Tc-99m) can clarify the etiology if needed. False negatives can occur with delayed TSH rise, central hypothyroidism, or inadequate specimen timing.

Treatment

Levothyroxine at 10-15 mcg/kg/day should be initiated within 2 weeks of life (ideally within the first week). Tablets should be crushed in breast milk or water, and soy formula should be avoided because it interferes with absorption. The goal is to normalize free T4 within 2 weeks and TSH within 1 month. Monitoring includes TSH and free T4 at 2 weeks, monthly for 6 months, then every 2-3 months until age 3. A trial off therapy at age 3 is considered if permanent hypothyroidism has not been confirmed (eutopic, normal-appearing gland).

<image>Diagram of neonatal thyroid screening algorithm showing initial TSH measurement, confirmatory serum testing, thyroid imaging, and treatment initiation timeline with developmental milestones at risk if untreated</image>

Acquired Hypothyroidism

Hashimoto Thyroiditis (Chronic Lymphocytic Thyroiditis)

Hashimoto thyroiditis is the most common cause of acquired hypothyroidism in iodine-sufficient regions. It involves autoimmune destruction of thyroid tissue with positive anti-thyroid peroxidase (TPO) and/or anti-thyroglobulin antibodies. Peak incidence is during adolescence with a female predominance of 2:1. It is associated with other autoimmune conditions including T1DM, celiac disease, Turner syndrome, Down syndrome, and Addison disease. The presentation includes goiter (firm, nontender, "pebbly" texture), fatigue, weight gain, cold intolerance, constipation, dry skin, growth deceleration, delayed puberty, and menstrual irregularities.

Other Causes

Additional causes include iodine deficiency (globally the most common cause), medications (lithium, amiodarone, antiepileptics), post-surgical or post-radioiodine ablation, and central hypothyroidism from pituitary or hypothalamic lesions or cranial radiation.

Evaluation

TSH is elevated in primary hypothyroidism and low or normal in central hypothyroidism. Free T4 is low. Anti-TPO and anti-thyroglobulin antibodies are positive in Hashimoto thyroiditis. Thyroid ultrasound is indicated if nodularity or asymmetry is palpated.

Treatment

Levothyroxine replacement at a typical pediatric dose of 2-4 mcg/kg/day (adolescents closer to 1-2 mcg/kg/day) is the standard treatment. TSH and free T4 should be monitored every 4-6 weeks after dose changes, then every 6-12 months when stable. Some patients with Hashimoto thyroiditis present with transient hashitoxicosis (a hyperthyroid phase) before becoming hypothyroid.

<image>Clinical illustration comparing a child with untreated hypothyroidism (short stature, puffy face, dry skin, coarse hair, delayed reflexes) alongside normal thyroid anatomy and a goiter with lymphocytic infiltration seen in Hashimoto thyroiditis</image>

Hyperthyroidism

Graves Disease

Graves disease is the most common cause of hyperthyroidism in children, accounting for more than 95% of pediatric cases. It is caused by thyroid-stimulating immunoglobulins (TSI) that activate the TSH receptor. Peak incidence is in adolescent girls with a female-to-male ratio of 5:1. Symptoms include weight loss, heat intolerance, tremor, tachycardia, palpitations, anxiety, emotional lability, hyperactivity, diarrhea, proptosis, lid lag, thyroid bruit, and diffuse goiter. Thyroid storm is rare but life-threatening, presenting with extreme tachycardia, hyperthermia, and altered mental status requiring ICU management.

Evaluation

TSH is suppressed (below 0.1 mIU/L). Free T4 and/or free T3 are elevated. TSI or thyroid receptor antibodies (TRAb) are positive. Thyroid uptake scan shows diffuse increased uptake, though this is not always needed if the clinical picture is clear.

Treatment Options

Antithyroid drugs (ATDs) are the first-line treatment. Methimazole is preferred (PTU is avoided in children due to hepatotoxicity risk, except in thyroid storm or the first trimester of pregnancy). Methimazole is dosed at 0.2-0.5 mg/kg/day, with monitoring of CBC and LFTs and counseling on rare but serious side effects (agranulocytosis, hepatitis). The remission rate after 1-2 years of therapy is approximately 20-30% in children.

Radioactive iodine (RAI) ablation is a definitive therapy for children over 10 years who fail or cannot tolerate ATDs. It results in permanent hypothyroidism requiring levothyroxine. Thyroidectomy is considered for large goiters, very young children, or when RAI is contraindicated, with risks including hypoparathyroidism and recurrent laryngeal nerve injury. Beta-blockers (propranolol or atenolol) provide symptomatic relief of tachycardia and tremor while awaiting ATD effect.

<image>Comparison of a child with Graves disease showing proptosis, diffuse goiter, and tachycardia versus a child with Hashimoto thyroiditis showing goiter, growth deceleration, and fatigue, with diagnostic lab findings for each condition</image>

Thyroid Nodules and Cancer

Thyroid nodules are less common in children than adults but have a higher malignancy rate (approximately 25% versus 5%). Papillary thyroid carcinoma is the most common pediatric thyroid malignancy. Evaluation includes TSH, thyroid ultrasound (features concerning for malignancy: solid, hypoechoic, microcalcifications, irregular borders), and fine-needle aspiration (FNA) for nodules greater than 1 cm or with suspicious features. Treatment is total thyroidectomy, radioiodine ablation, and TSH suppression with levothyroxine.

Clinical Pearls

Congenital hypothyroidism treatment must begin by 2 weeks of life to prevent irreversible neurodevelopmental damage. Children with T1DM, celiac disease, Turner syndrome, and Down syndrome should be screened for thyroid disease annually. Methimazole, not PTU, is the first-line antithyroid drug in children; PTU carries a black-box warning for hepatic failure in pediatrics. A thyroid nodule in a child has a much higher probability of malignancy compared to adults, so ultrasound should always be obtained and FNA considered. Hashitoxicosis can mimic Graves disease; checking autoantibodies helps distinguish the two (TSI positive in Graves; TPO positive in Hashimoto).

References

1. Leger J, Olivieri A, Donaldson M, et al. European Society for Paediatric Endocrinology Consensus Guidelines on Screening, Diagnosis, and Management of Congenital Hypothyroidism. J Clin Endocrinol Metab. 2014;99(2):363-384.
2. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism. Thyroid. 2016;26(10):1343-1421.
3. Bauer AJ, Francis GL. Evaluation and Management of Thyroid Nodules in Children. Curr Opin Pediatr. 2016;28(4):536-544.
4. Rivkees SA. Pediatric Graves' Disease: Management in the Post-Propylthiouracil Era. Int J Pediatr Endocrinol. 2014;2014:10.

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