ESPE Abstracts

Background: Neonatal hyperthyroidism is almost always transient and related to the passage of maternal thyroid stimulating immunoglobulins (TSI). Positive TSI levels in a neonate is often diagnostic of neonatal Graves disease. The manifestation of symptoms has not been well characterized in premature infants.

Clinical Case: A female infant was delivered at 27×4/7 weeks gestational age, with a birth weight of 827 g. Her mother was diagnosed with Graves disease 2 weeks prior to delivery, but was not started on any medications. Thyroid function tests obtained on the infant on DOL 2, showed a low TSH of 0.003 μIU/ml and normal FT4 of 1.4 ng/dl. TSI levels were negative. By DOL 7, the infant developed tachycardia. Repeat labs revealed a TSH of 0.005 μIU/ml and FT4 of 4.3 ng/dl. Methimazole was started at 0.4 mg/kg per day, as well as propranolol at 0.5 mg/kg per day divided into three doses. Four days after methimazole was started, TSH remained low, but FT4 normalized to 1.3 ng/dl and tachycardia resolved. By DOL 14, elevated liver enzymes led to discontinuation of methimazole. On DOL 18, tachycardia reoccurred, and FT4 had again increased to 4.7 ng/dl. TSI was again negative and liver enzymes had normalized. Methimazole and propranolol were restarted at lower doses (0.25 mg/kg per day and 0.4 mg/kg per day respectively). Within 3 days of therapy, FT4 normalized to 1.3 ng/dl. Other studies revealed a high thyroglobulin level of 131.9 ng/ml (2.8–40.9), negative thyroglobulin antibodies, high anti-TPO antibodies of 37.4 IU/ml and high thyrotropin receptor antibodies at 40% (normal<17%). Methimazole was continued for 7 weeks. FT4 remained normal, and TSH continued to be suppressed. By DOL 45, methimazole was stopped. Repeat labs done 1 week later showed a TSH of 0.013 μIU/ml and FT4 1.3 ng/dl. Thyrotropin receptor antibody was 20% at that time. Methimazole was restarted at 0.15 mg 3 times/week. One week later, she had a TSH of 0.022 μIU/ml and FT4 of 1.0 ng/dl. Methimazole was discontinued.

Conclusion: This patient had TSI-negative neonatal Graves that was very sensitive to methimazole. The suspected cause for this infant’s neonatal hyperthyroidism was the thyrotropin receptor antibodies, stimulating the TSH receptor. Patient’s FT4 normalized almost immediately after starting methimazole. It was not until her thyroid receptor autoantibody levels declined that methimazole could be discontinued. In TSI negative patients with suspected Graves disease, another lab study to be considered would be thyrotropin receptor antibody.