title: Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed.
abstract: 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 T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T(4) 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 T(4) 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 1:35000) warrants early detection and treatment to minimize the risk of cerebral damage. A T(4)-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.
authors.affiliation: Academic Medical Center, Emma Children's Hospital, Department of Pediatric Endocrinology, University of Amsterdam, 1100 DE Amsterdam, The Netherlands. m.j.kempers@amc.uva.nl
authors.forename: Marlies J E
authors.initials: MJ
authors.lastname: Kempers
authors.forename: David A
authors.initials: DA
authors.lastname: van Tijn
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
authors.forename: Jan J M
authors.initials: JJ
authors.lastname: de Vijlder
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Wiedijk
authors.forename: Thomas
authors.initials: T
authors.lastname: Vulsma
mesh_terms: D013956:Antithyroid Agents / Q000627:therapeutic use; D005260:Female; D005312:Fetal Blood; D006111:Graves Disease / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D006980:Hyperthyroidism / Q000151:congenital* / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use
chemical_list: D013956:Antithyroid Agents; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D013974:Thyroxine