Maternal Graves Disease and Abnormal CYP2D6 Genotype with Fetal Hyperthyroidism

Abstract

<jats:sec><jats:title>Objective:</jats:title><jats:p> Fetal hyperthyroidism is a rare yet potentially fatal complication of past or present maternal Graves disease (GD). Our objective was to present a unique case of fetal hyperthyroidism in a mother with a prior history of GD and a cytochrome P450 2D6 (CYP2D6) polymorphism. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> The clinical course in addition to serial laboratory and imaging results are presented. These include thyroid-stimulating hormone, free thyroxine, and thyrotropin receptor antibody levels, as well as fetal ultrasound, doppler fetal heart rate, and cordocentesis testing. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> A 27-year-old with a history of GD previously treated with radioiodine and a known cytochrome P450 polymorphism was referred to an endocrinology clinic at 17 weeks gestation for evaluation and management of fetal thyrotoxicosis. Despite close follow-up with a multidisciplinary care team and an aggressive “block and replace” treatment approach, progressive disease resulted in intrauterine fetal demise at 28 weeks gestation. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> To our knowledge, this is the first published case report of fetal hyperthyroidism accompanied by a maternal CYP2D6 polymorphism. We hypothesize that the maternal CYP2D6 poor metabolizer phenotype prevents formation of antithyroid drug (ATD) metabolites and thus decreases the efficacy of ATD treatment. We suggest this as an area of future research. </jats:p></jats:sec>

Fetal Hyperthyroidism Secondary to Maternal Basedow–Graves' Disease

“…The most common management scenario in children of mothers with maternal hyperthyroidism due to Graves' disease is neonatal hyperthyroidism with several cases being described in the literature. Due to the severe consequences of fetal hyperthyroidism 8 , screening during pregnancy is mandatory in mothers with a history of active Graves' disease or those who have been treated with radioiodine and/or thyroidectomy 4 . Laboratory work-up with TRAbs and thyroid function levels immediately after pregnancy diagnosis is suggested in the literature 4,9 .…”