A term infant born to a mother with gestational diabetes and a history of hypothyroidism presented with seizures on the 6th day of life that responded to L-thyroxine, in a report from The Children’s National Medical Center, Washington, DC. The mother had not required thyroid replacement therapy during or for 9 years before this pregnancy. She was taking daily antidepressants for major depression. Birth complications included meconium in the amniotic fluid, cesarean section for abnormal fetal heart rate, neonatal respiratory distress, and treatment in the neonatal intensive care unit. The Apgar scores were 8 and 9 at 1 and 5 minutes. Birth weight was at the 10-25th %, length <10th %, and head circumference of 34 cm (25-50th %). Cranial sutures were wide and the posterior fontanel measured 4 cm. Oxygen saturation was 95%, and respiratory distress resolved in a few hours. Rhythmic jerking started in the right arm on day 6 and became generalized. Seizures were unresponsive to an initial phenobarbital bolus, and were controlled by addition of lorazepam and phenytoin. Lumbar puncture showed normal CSF, and blood electrolytes, glucose, and amino acids and urine organic acids were normal. EEG, CT scan, and MRI were normal. Thyroid function studies on day 9 were as follows: TSH 0.67 (N: 0.4-4.7 uIU/mL); free T4 0.5 (N: 0.7-1.8 ng/dL); free T3 1.41 (N: 1.5-3.5 pg/mL). On day 15 after L-thyroxine 25 ug/day, the TSH was 0.71 and free T4 1.4. Maternal TSH and T4 were normal. Seizures stopped and antiepileptic medications were discontinued, with one relapse at 2 months associated with hypothyroidism (hoarse cry, wide fontanel, delayed bone age, temperature instability). Seizures responded to an increase in thyroxine. The neurologic evaluation at 6 months follow-up was normal. [1]

COMMENT. Multiple factors may have contributed to the seizures in this case (hypoxic-ischemic encephalopathy, maternal diabetes and antidepressants) in addition to hypothyroidism. The authors argue against alternative causes and find the response to thyroxine and successful withdrawal of AEDs to be strongly supportive of an association. The expected rise in TSH with congenital hypothyroidism may be delayed in some newborns, and the initial low TSH and low free T4 are compatible with the diagnosis. (Nelson Pediatrics gives newborn normal values: TSH 1.0-9.1 and T4 2.0-4.9). The routine neonatal metabolic screening may be normal, as in this infant, and this finding should not discourage further testing for possible hypothyroidism as a cause of neonatal seizures refractory to therapy. Seizures are known to complicate myxedema in adults but are rare with congenital hypothyroidism.