SUN-517 Methimazole-Induced Neutropenia in Premature Twins with Graves’ Disease

Abstract

Introduction: Neonatal Graves’ disease (NGD) occurs in approximately 1-5% of infants born to women with Graves’ disease. It is caused by trans-placental crossing of thyroid stimulating immunoglobulin (TSI) antibodies during third trimester. Hyperthyroidism during pregnancy can lead to craniosynostosis, goiter, premature bone maturation, developmental delay or even heart failure in the neonate. Neonatal Hyperthyroidism is usually transient and resolves in few weeks. Treatment consists of beta blockers and Methimazole. Studies in adults recommend discontinuing of Methimazole if patients develop neutropenia. However due to lack of alternatives, we present a case of continued use of Methimazole with neutropenia in newborn twins.Case Report:33 weeks gestational age mono-chorionic/di-amniotic twins born to a 34-year-old woman with poorly controlled hyperthyroidism. Mother diagnosed with Graves’ disease during 2nd trimester with poor control throughout pregnancy. At the time of delivery, maternal TSH was <0.005uIU/mL(0.358-3.74uIU/mL) and FT4 2.18ng/dL(0.76-1.46ng/dL). Antenatal ultrasound at 32 weeks showed homogeneous enlargement of fetal thyroid glands with increased vascularity in both twins. Babies found to have diffuse goiter and exophthalmos at birth. Thyroid tests remained normal for first 3 days of life. By day 3, babies labs showed TSH <0.005uIU/mL, FT4 -8 ug/dL and TSI >700%. Baseline CBC showed ANC of 4.95K/mm3. Babies were started on Methimazole 0.5mg/kg/day and Propranolol 2mg/kg/day. TFTs fluctuated throughout their stay in NICU and they developed neutropenia with ANC 1.23K/mm3 on day 20 of life. Methimazole was initially discontinued then restarted at 0.25 mg/kg/day 3 days later. There is no recommended protocol for restarting Methimazole. Further follow up showed persistent neutropenia despite multiple dose adjustments in Methimazole, including dosing every other day. ANC was maintained around 800-1100K/mm3. At age 2 months, Methimazole was discontinued completely after TSI antibodies decreased to 400%. ANC remained low until 6 months of life, even after discontinuing Methimazole. Both babies ultimately developed central hypothyroidism and were started on l-thyroxine.Discussion:NGD can range anywhere from transient hyperthyroidism to persistent central hypothyroidism. Early diagnosis and treatment is crucial to prevent significant morbidity and mortality. Methimazole is the only approved treatment at this age, and management of Methimazole-induced neutropenia has not been established. Adult studies recommend discontinuing Methimazole in context of neutropenia; we took an approach of decreasing dose gradually. Further studies are needed to establish step-wise approach in managing Methimazole-induced neutropenia.