Overview
This lecture reviews congenital hypothyroidism in newborns, focusing on thyroid function, causes, clinical features, diagnosis, management, and outcomes, emphasizing early detection and treatment.
Thyroid Gland Function and Regulation
- The thyroid gland forms in the first trimester and migrates to the anterior neck.
- Its main function is to secrete thyroid hormones: T4 (thyroxine, a prohormone) and T3 (triiodothyronine, active form).
- Thyroid hormone production is regulated by the anterior pituitary's TSH (thyroid stimulating hormone).
- Feedback loops: Low T4/T3 triggers increased TSH; high T4/T3 suppresses TSH.
- Hypothalamus releases TRH (thyrotropin-releasing hormone), regulating the pituitary.
Causes of Congenital Hypothyroidism
- Most cases are due to thyroid gland abnormalities (dysgenesis: absent, ectopic, or malformed thyroid).
- A small percentage relate to genetic defects in hormone production or pituitary dysfunction.
- Maternal factors: antibodies (Graves disease) or medications (methimazole, PTU) can transiently suppress neonatal thyroid.
- Iodine deficiency is a preventable global cause.
- Central hypothyroidism is rare, usually involves pituitary (low TSH, low free T4), often with other pituitary hormone deficiencies.
Clinical Manifestations
- Symptoms in newborns may be subtle or absent; common signs: jaundice, poor feeding, and hypoglycemia.
- Classical features (exam-worthy): macroglossia (large tongue), persistent open posterior fontanel (>0.5 cm), umbilical hernia.
- Other symptoms: constipation, bradycardia, coldness, growth and neurodevelopmental delays.
Diagnosis and Newborn Screening
- Universal newborn screening tests for hypothyroidism, typically between days 1-7 of life.
- Most states check TSH, some check T4.
- High TSH with low free T4 suggests primary hypothyroidism; low TSH and low T4 suggests central origin.
- False positives can occur from certain drugs or illness.
- Critical to follow up on abnormal screens to ensure prompt diagnosis.
Management and Treatment
- If TSH >40 mIU/L on newborn screen: start levothyroxine immediately, before confirmation.
- If TSH 20-40 mIU/L on repeat labs: start medication.
- Initial dose: 10–15 mcg/kg/day levothyroxine (oral or IV if needed).
- Goal: normalize TSH and free T4 within 2–4 weeks; check labs every 1–2 weeks until normalized, then monthly for 6 months.
- Pediatric endocrinologist should supervise ongoing care.
- History should assess maternal thyroid disease, family history, and medications.
Outcomes
- Early treatment prevents neurodevelopmental deficits; delay increases risk for cognitive impairment.
- Lifelong medication is needed if the thyroid gland is absent or severely dysgenic; transient causes may resolve.
- Retest thyroid function at age 3 to determine if therapy can be stopped.
Key Terms & Definitions
- Congenital Hypothyroidism — Low thyroid hormone levels present at birth.
- Thyroxine (T4) — Primary hormone produced by the thyroid, mostly converted to T3 in the body.
- Triiodothyronine (T3) — Active thyroid hormone.
- TSH (Thyroid Stimulating Hormone) — Pituitary hormone stimulating thyroid hormone production.
- Thyroid Dysgenesis — Abnormal development or location of the thyroid gland.
- Central Hypothyroidism — Thyroid hormone deficiency due to pituitary or hypothalamic dysfunction.
- Levothyroxine — Synthetic thyroid hormone used for treatment.
Action Items / Next Steps
- List five symptoms of hypothyroidism.
- Describe expected lab values in a baby with a small ectopic thyroid.
- Explain why high-dose thyroid medication should be started by two weeks of life.