Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys.

Abstract

The differentiation of constitutional delayed puberty (CDP) from gonadotrophin deficiency (GD) in boys at referral poses a difficult challenge. The effectiveness of the GnRH agonist (GnRH-a) test in distinguishing between the two conditions was evaluated and compared with findings of the GnRH and hCG stimulation tests. PATIENTS, METHODS AND DESIGN: The study sample included 32 prepubertal boys aged 14 years or older. Thirteen entered spontaneous puberty within 1 year of referral (group A) and 19 remained prepubertal (group B). All underwent the GnRH test (Relefact, Hoechst AG, 0.1 mg/m2 i.v. in one bolus), GnRH-a test (Decapeptyl, Ferring GmbH, 0.1 mg/m2 s.c.) and hCG stimulation (Chorigon, Teva, 1500 units i.m. on three alternate days) at 1-week intervals. All tests were performed at referral at 0800 h. Blood samples were collected before testing and at 30 and 60 min (GnRH test) or 4 h (GnRH-a) for LH and FSH determination, and before testing and at 4 h (GnRH-a) or on the seventh day (hCG) after stimulation for serum testosterone measurement. The LH response to GnRH-a and the testosterone response to hCG stimulation were significantly higher in group A (LH, mean +/- SD 20.4 +/- 7.5 mIU/ml, range 10.8-32.6; testosterone, mean +/- SD 18.0 +/- 5.9 nmol/l, range 9.4-26, P < 0.0001) than in group B (LH, mean +/- SD 2.3 +/- 2.0 mIU/ml, range 0.7-6.9; testosterone, mean +/- SD 1.0 +/- 0.7 nmol/l, range 0.7-3.2), with no overlap between the groups. The cut-off for the LH response to GnRH-a was 8.0 mIU/ml, and for the testosterone response to hCG, 8 nmol/l. There were also significant differences between the groups in mean basal serum LH and FSH (LH, 1.1 +/- 0.5 vs. 0.6 +/- 0.2 mIU/ml, P < 0.05; FSH, 2.2 +/- 2.0 vs. 0.4 +/- 0.3 mIU/ml, P < 0.02) and their response to GnRH (LH, 11.4 +/- 4.4 vs. 2.7 +/- 1.1 mIU/ml, P < 0.0001; FSH, 5.1 +/- 3.4 vs. 2.5 +/- 2.4 mIU/ml, P < 0.0001), and mean serum testosterone level at 4 h after GnRH-a administration (1.9 +/- 1.0 vs. 0.9 +/- 0.4 nmol/l, P = 0.002), but all showed a great overlap in range. Mean age, testicular volume and basal serum testosterone levels were similar in the two groups at referral. One year later, the testicular volume of group A (5.0-12.0 ml) was significantly larger than that of group B (1.0-3.0 ml, P < 0.0001), which remained unchanged on re-examination 3.0 +/- 0.5 years later. The GnRH-agonist test and the repeated-injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.