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Central Congenital Hypothyroidism due to Gestational Hyperthyroidism: Detection Where Prevention Failed

Academic Medical Center, Emma Children’s Hospital, Department of Pediatric Endocrinology, University of Amsterdam, 1100 DE Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: Marlies J. E. Kempers, M.D., Academic Medical Center, University of Amsterdam, G8-205, Emma Children’s Hospital AMC, Department of Pediatric Endocrinology, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: m.j.kempers{at}amc.uva.nl.

Much worldwide attention is given to the adverse effects of maternal Graves’ disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves’ disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves’ disease. Nine mothers were diagnosed after pregnancy, the majority after their children were detected with CCH by neonatal screening. Four mothers were diagnosed during pregnancy and treated with antithyroid drugs since diagnosis. Another four mothers were diagnosed before pregnancy, but they used antithyroid drugs irregularly; free T₄ concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T₄ concentrations (range 0.3–0.9 ng/dl, 3.9–11.5 pmol/liter); plasma TSH ranged between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen children needed T₄ supplementation. Because all mothers were insufficiently treated during pregnancy, it is hypothesized that a hyperthyroid fetal environment impaired maturation of the fetal hypothalamic-pituitary-thyroid system. The frequent occurrence of this type of CCH (estimated incidence 1:35,000) warrants early detection and treatment to minimize the risk of cerebral damage. A T₄-based screening program appears useful in detecting this type of CCH. However, the preferential and presumably best strategy to prevent CCH caused by maternal Graves’ disease is preserving euthyroidism throughout pregnancy.

Abbreviation: CH, Congenital hypothyroidism.

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