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Role of Gonadotropin-Releasing Hormone and Human Chorionic Gonadotropin Stimulation Tests in Differentiating Patients with Hypogonadotropic Hypogonadism from Those with Constitutional Delay of Growth and Puberty

London Centre for Paediatric Endocrinology at Great Ormond Street Hospital for Children and University College London Hospitals (T.Y.S., A.A., P.C.H., M.T.D.), London WC1N 3JH, United Kingdom; and Developmental Endocrinology Research Group (A.M., P.C.H., M.T.D.), Institute of Child Health, University College London, London WC1N 1EH, United Kingdom

Address all correspondence and requests for reprints to: Professor Mehul T. Dattani, Professor of Pediatric Endocrinology, Developmental Endocrinology Research Group, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom. E-mail: m.dattani{at}ich.ucl.ac.uk.

Background: Delayed puberty can be due to either constitutional delay of growth and puberty (CDGP) or hypogonadotropic hypogonadism (HH). Differentiating between the two using current testing can be difficult. We assessed the utility of a GnRH test in combination with a 3-d and 19-d human chorionic gonadotropin (HCG) test to discriminate between the two conditions.

Methods: We performed a retrospective analysis of 43 boys with pubertal delay who required pubertal induction with testosterone. All were followed through puberty; 29 were subsequently diagnosed with CDGP and 14 with HH. A standard GnRH test (2.5 µg/kg) was undertaken and was followed by a short [3 d; n = 38 (13 HH, 25 CDGP)] or extended [19 d; n = 31 (12 HH, 19 CDGP)] HCG stimulation test, or both [n = 27 (11 HH, 16 CDGP)]. Receiver operating characteristic analysis was performed to assess the performance of the tests.

Results: Peak testosterone concentrations to both 3-d and 19-d HCG tests were significantly lower in patients with HH compared with CDGP. The 19-d test performed better than the 3-d test, and a combination of the LHRH, 3-d and 19 d HCG test [peak LH cutoff, 2.8 U/liter; peak 3-d testosterone cutoff, 1.04 µg/liter (3.6 nmol/liter); peak 19-d testosterone cutoff, 2.75 µg/liter (9.5 nmol/liter)] gave a sensitivity and a specificity of 100%.

Conclusions: Our data suggest that a GnRH test in combination with both a 3-d and 19-d HCG test may aid in differentiating between CDGP and HH.

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