OBJECTIVE: The aim of the study was to evaluate the IGF-I generation test (IGF-I gen) as a possible indirect test of Growth Hormone (GH) secretory status. METHODS: Sixty-five GH deficient (GHD 1 and 2) and 86 control children were studied. Children in the GHD-1 subgroup (n=33) had low GH values (<10μg/L) after clonidine and levo-dopa while those in the GHD-2 subgroup (n=32) had normal GH values after pharmacologic provocation but low 24-hour GH secretory rates compared to 187 Normal Statured (NS) children. Of the 86 controls, who underwent IGF-I gen, 50 were NS and 36 Short-Statured (SS). Serum IGF-I was measured prior to and daily during hGH administration (hGH 0.033 mg/kg/day x 4 days). RESULTS: The prepubertal and pubertal GHD-1 and GHD-2 children had low baseline IGF-I values but their peak IGF-I values during the IGF-I gen reached those of the controls. The percent increase of IGF-I during the test was greater in the GHD groups than in the controls; in the prepubertal groups: 516±58% in the GHD-1, 433±50 % in the GHD-2, 106±12 % in the NS, and 102±18 % in the SS (p=0.001); in the pubertal groups: 191±28 % in the GHD-1, 141±20 % in the GHD-2, 48±8 % in the NS, and 61±17 % in the SS (p=0.003). CONCLUSIONS: The IGF-I response during the IGF-I gen seems to reflect the GH status in children.

Background: The combined growth hormone-releasing hormone and growth hormone-releasing peptide-6 (GHRH + GHRP-6) test is most potent in evaluating GH secretion. Aims: To assess its capability in children with GH deficiency and low spontaneous GH secretion (GH neurosecretory dysfunction). Methods: 35 children with GH <10 µg/l after levo-dopa/clonidine (GHD), 15 with normal provocative tests but abnormal 24-hour spontaneous GH secretion (GHND), and 20 controls (C) were given 1 µg/kg of GHRH and GHRP-6 i.v. and GH (µg/l) was measured at –15, 0, 5, 10, 15, 30, 45 and 60 min. Results: Six were nonresponders to the combined test, with significantly lower peak GH 20.7 (7.8–31.8) than C and the rest of the patients (responders). Peak GH was similar between prepubertal (PP) controls 167 ± 88, GHD 202 ± 110 and GHND 155 ± 83. Pubertal (P) controls had higher peak GH 328 ± 149 than P-GHD 203 ± 105 and P-GHND 186 ± 105. While P-C had higher peak GH than PP-C, PP and P children had similar responses within the GHD and GHND groups. Conclusions: The GHRH + GHRP-6 test detects children with severe GH insufficiency. Patients with GHD respond similarly to those with GHND, indicating a possible hypothalamic GH neuroregulatory dysfunction in GHD. Responders to the combined test may be eligible for treatment with a synthetic GH secretagogue.