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This version published online on October 17, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-0689
A more recent version of this article appeared on January 1, 2007
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Submitted on March 29, 2006
Accepted on October 10, 2006

Early assessment of hypothalamic-pituitary-gonadal function in patients with congenital hypothyroidism of central origin

David A. van Tijn MD*, Eelco J. Schroor MD, PhD, Henriette A. Delemarre-van de Waal MD, PhD, Jan J.M. de Vijlder PhD, and Thomas Vulsma MD, PhD, MSc

Department of Pediatric Endocrinology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Pediatrics, subdivision Endocrinology, VU University Medical Center, Amsterdam, The Netherlands; Current address: Department of Pediatrics, Isala Clinics, Zwolle, The Netherlands

* To whom correspondence should be addressed. 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 gonadotropin-releasing hormone (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. 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. Department of Pediatric Endocrinology, Emma Children's Hospital, Academic Medical Center, University of Amsterdam (referral center).

Patients. Fifteen neonates (5 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.

Results. GnRH tests at 3 months of age showed a pattern indicative of endogenous GnRH stimulation in 9 infants and a blunted response in 6. Baseline Gn and sex hormone concentrations except estradiol (P = 0.053) were significantly different between responders and non-responders.

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.
Key words: hypothalamus-pituitary-gonad axis • gonadotropin deficiency • multiple pituitary hormone deficiency • GnRH test • hypogenitalism • cryptorchidism • posterior pituitary ectopia • neonatal screening • congenital hypothyroidism of central origin (CH-C)




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D. A. van Tijn, J. J. M. de Vijlder, and T. Vulsma
Role of the Thyrotropin-Releasing Hormone Stimulation Test in Diagnosis of Congenital Central Hypothyroidism in Infants
J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 410 - 419.
[Abstract] [Full Text] [PDF]


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