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Early Assessment of Hypothalamic-Pituitary-Gonadal Function in Patients with Congenital Hypothyroidism of Central Origin

Department of Pediatric Endocrinology (D.A.v.T., J.J.M.d.V., T.V.), Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands; and Department of Pediatrics (E.J.S., H.A.D.v.d.W.), Subdivision Endocrinology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands

Address all correspondence and requests for reprints to: David A. van Tijn, M.D., Department of Pediatric Endocrinology, Emma Children’s Hospital, G8-205, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail: tijn1{at}planet.nl.

Context: Early recognition of gonadotropic dysfunction could enable well-timed growth and maturation and prevent damage to gonads and external genitalia. The adaptation of the Dutch neonatal screening program for congenital hypothyroidism in the mid 1990s resulted in enhanced detection of congenital hypothyroidism of central origin (CH-C), with high likelihood of multiple pituitary hormone deficiency, including gonadotropin (Gn) deficiency.

Objective: We analyzed GnRH test results and baseline Gn and sex hormone measurements in 15 infants with CH-C to examine these diagnostic tools for assessment of the integrity of the hypothalamus-pituitary-gonad axis in young infants.

Design: In a nationwide prospective study (1994–1996), patients were referred to our department if neonatal CH screening results were indicative of CH-C. When CH-C was confirmed, GnRH tests and baseline Gn and sex hormone measurements took place at the age of 3 months, when euthyroid status had been accomplished by T₄ supplementation, and if necessary, cortisol supplementation was installed.

Setting: The study took place at the Department of Pediatric Endocrinology, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam (referral center).

Patients: The study included 15 neonates (five girls and 10 boys) with CH-C, detected by neonatal screening, in whom investigation of the hypothalamus-pituitary-gonad axis could be performed at 3 months of age.

Main Outcome Measures: Results of GnRH tests and baseline Gn and sex hormone measurements were assessed.

Results: GnRH tests at 3 months of age showed a pattern indicative of endogenous GnRH stimulation in nine infants and a blunted response in six. Baseline Gn and sex hormone concentrations except estradiol (P = 0.053) were significantly different between responders and nonresponders.

Conclusions: The GnRH test and baseline measurements of Gn and sex hormone serum concentrations at 3 months of age are promising options in the assessment of hypothalamic-pituitary-gonadal function in infants with CH-C of both sexes.

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