Methimazole Associated Neutropenia in a Preterm Neonate Treated for Hyperthyroidism

Abstract

Maternal Graves' disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves' disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves' disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroid, she was treated with methimazole, iodine, and a beta-blocker. 20 days after the initiation of methimazole, she developed neutropenia. The neutrophil counts started to improve immediately after the initiation of the weaning of methimazole. To the best of our knowledge, this is the first case reported in the literature of methimazole induced neutropenia in a preterm infant being treated for neonatal Graves' disease.

Management of Neonates Born to Mothers With Graves’ Disease

“…Less commonly, hyperthyroidism is (initially) treated with repeated doses of iodide instead of ATDs. 18,[69][70][71] In extremely ill newborns requiring admission to a NICU for respiratory or cardiac support, a short course of glucocorticoids, which inhibit thyroid hormone secretion and impair peripheral deiodination of T4 to T3, may be necessary.…”

“…To the best of our knowledge, only a single case report described the development of neutropenia in a preterm (GA 30 weeks) neonate treated with MMI who recovered after decreasing the dose. 71 Prematurity is not a contraindication to ATD use. However, in 1 study, 2 extremely preterm newborns (GA 25 weeks) demonstrated an unusually rapid (within 48 hours) decrease in fT4 levels after starting carbimazole, indicating that is important to monitor TFTs more closely in preterm newborns.…”

“…A range from 0.2 to 1 mg/kg per day divided in 1 to 3 doses, with a typical dose of 0.2 to 0.5 mg/kg per day, has been reported. 14,59,64,66,71,73 For full-term newborns, we therefore recommend initiating MMI at 0.625 mg twice daily (0.4 mg/kg per day for a 3-kg newborn). The infant should be assessed clinically and biochemically on a weekly base until stable, then every 1 to 2 weeks with titration of MMI dose as tolerated.…”

Neutropenia Associated with Methimazole Therapy in A 4.7-year Girl with Graves’ Disease.

“…To our knowledge, the cut-off point of severe neutropenia associated with antithyroid therapy is not defined, however in adults it is usually to be defined as ANC<500 cell/ ul associated with clinical manifestations like fever, sore throat and oral ulcers (5). Our case had bilateral parotitis, fever, sore throat and one oral ulcer associated with decreasing neutropenic count and reached an ANC nadir level of 431 cell/ ul.…”