Snapshot A 6-week-old girl presents with lethargy, difficulty feeding, and hypotonia. Her parents report that she was healthy and did not have any apparent symptoms at birth. This is her first time seeing a doctor. On exam, she appears jaundiced and has a large tongue that is protruding. Introduction Clinical definition thyroid hormone deficiency present at birth cretinism refers to the state of developmental delay secondary to untreated congenital hypothyroidism Genetics defects in T4 or triiodothyronine (T3) synthesis Epidemiology Demographics most common neonatal endocrine disorder 2:1 female-to-male ratio Risk factors gestational age > 40 weeks ETIOLOGY Pathogenesis thyroid hormone is critical for normal brain growth and myelination during the first trimester, the fetus is dependent on maternal thyroxine (T4) with gradual fetal thyroid secretion after major etiologies include most common in developed countries login to view 2 more bullets most common in underdeveloped countries login to view 1 more bullet maternal antithyroid antibodies that cross the placenta is a rare cause Presentation Symptoms normal APGAR, asymptomatic at birth presents at 6-12 weeks poor feeding failure to thrive lethargy constipation Physical exam low body temperature large anterior fontanelle jaundice coarse facies with macroglossia umbilical hernia hypotonia developmental delay mottled, dry skin Studies Diagnostic testing diagnostic approach screening at 3 days old or within 7 days of birth login to view 2 more bullets labs login to view 2 more bullets imaging login to view 6 more bullets Differential Neonatal hypothyroxinemia distinguishing factor ↓ thyroid hormone but TSH is not elevated, occurs in premature or ill infants Pediatric hypopituitarism distinguishing factor loss of other axes in addition to ↓ T4 including ↓ cortisol, ↓ sex steroids, ↓ growth hormone, and ↓ antidiuretic hormone DIAGNOSIS Diagnostic criteria ↑ TSH and ↓ T4 imaging can help differentiate etiology Treatment Management approach early diagnosis via neonatal screening allows for early intervention routine clinical and laboratory monitoring formal developmental and psychoneurological evaluations First-line levothyroxine replacement Complications Intellectual disability Growth failure Prevention Prevention by newborn screening by law Dietary iodine supplementation can prevent endemic cretinism but is not indicated for sporadic congenital hypothyroidism Prognosis Early diagnosis and treatment improves outcomes and patients can develop normally The most common preventable cause of intellectual disability