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Sex-Specific Impact of Congenital Hypothyroidism due to Thyroid Dysgenesis on Skeletal Maturation in Term Newborns

Service d’Endocrinologie Pédiatrique (G.V.V., L.B., J.L.), Hôpital Robert Debré, 75019 Paris, France; and Institut National de la Santé et de la Recherche Médicale U149, Recherche Épidémiologique en Santé Périnatale et Santé des Femmes (B.L., K.S.), 94800 Villejuif, France

Address all correspondence and requests for reprints to: Guy Van Vliet, M.D., Service d’Endocrinologie, Hôpital Sainte-Justine, 3175 Côte Sainte-Catherine, Montréal H3T 1C5, Québec, Canada. E-mail: gvanvliet{at}justine.umontreal.ca.

Newborns with severe congenital hypothyroidism (often defined by the absence of knee epiphyses at diagnosis) are still at risk of loss of intellectual potential despite early treatment. Although there is no significant sexual dimorphism in the age at appearance and size of the knee epiphyses in normal newborns, it was our clinical impression that these epiphyses were more often absent in hypothyroid newborn males than in affected females. Using the large French database of congenital hypothyroidism, we studied the presence or absence of knee epiphyses at diagnosis, as well as the length of gestation and the birth weight of 1827 term newborns with athyreosis or ectopic thyroid. Boys were twice as likely as girls to have absent epiphyses [odds ratio, 2.1 (95% confidence interval, 1.6–2.7), P < 0.001, after adjustment for etiology, plasma free T₄ concentration, and presence or absence of clinical signs at diagnosis, gestational age and birth weight]. Compared with the general population of French newborns, those with congenital hypothyroidism were more often born after a prolonged gestation (42 wk) and with a high birth weight (9% were above the 95th centile, as opposed to the expected 5%), regardless of sex. We conclude that the impact of congenital hypothyroidism on fetal skeletal maturation is sexually dimorphic. This may result from less efficient conversion of T₄ to T₃ by growth plate chondrocytes in males.

G.V.V. was supported by the Conseil National des Universités (France) as Professeur Associé at Université Paris VII-Denis Diderot and by the sabbatical leave program of the European Society for Paediatric Endocrinology (funded by Eli Lilly \|[amp ]\| Co.).

Abbreviations: CH, Congenital hypothyroidism; CHTD, CH due to thyroid dysgenesis.

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