Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients

Objective: It has been gradually realized that GH may have important physiological functions in adult humans. The biochemical diagnosis of adult GHD is established by provocative testing of GH secretion. The insulin-tolerance test (ITT) is the best validated. The ITT has been challenged because of its low degree of reproducibility and lack of normal range, and is contra-indicated in common clinical situations. Furthermore, in severely obese subjects the response to the ITT frequently overlaps with those found in non-obese adult patients with GHD. Design: The aim of the present study was to evaluate the diagnostic capability of four different stimuli of GH secretion: ITT, GHRH, GHRH plus acipimox (GHRH+Ac), and GHRH plus GHRP-6 (GHRH+ GHRP-6), in two pathophysiological situations: hypopituitarism and obesity, and normal subjects. Methods: Eight adults with hypopituitarism (four female, four male) aged 41-62 years (48.8 +/- 1.4 years), ten obese normal patients (five female, five male) aged 38-62 years (48.1 +/- 2.5 years), 2 with a body mass index of 34.2 +/- 1.2 kg/m(2), and ten normal subjects (five female, five male) aged 33-62 years (48.1 +/- 2.8 years) were studied. Four tests were performed on each patient or normal subject: An ITT (0.1 U/kg, 0.15 U/kg for obese, i.v., Omin), GHRH (100 mug, Lv., 0min), GHRH (100 mug, i.v, 0min) preceded by acipimox (250mg. orally, at -270min and -60min) (GHRH+Ac); and GHRH (100ug, i.v., 0min) plus GHRP-6 (100 mug, i.v., 0min) (GHRH + GHRP-6). Serum GH was measured by radioimmunoassay. Statistical analyses were performed by Wilcoxon rank sum and by Mann-Whitney tests. Results: After the ITT the mean peak GH secretion was 1.5 +/- 0.3 mug/l for hypopituitary, 10.1 +/- 1.7 mug/l (P < 0.05 vs hypopituitary) for obese and 17.8 +/- 2.0 mug/l (P < 0.05 vs hypopituitary) for normal. GHRH-induced GH secretion was 2 +/- 0.7 mug/l for hypopituitary, 3.9 +/- 1.2 mug/l (P = NS vs hypopituitary) for obese and 22.2 +/- 3.8 mug/l (P < 0.05 vs hypopituitary) for normal. After GHRH+Ac, mean peak GH secretion was 3.3 +/- 1.4 mug/l for hypopituitary, 14.2 +/- 2.7 mug/l (P < 0.05 vs hypopituitary) for obese and 35.1 +/- 5.2 mug/l (P < 0.05 vs hypopituitary) for normal. GHRH + GHRP-6 induced mean peak GH secretion of 4.1 +/- 0.9 mug/l for hypopituitary, 38.5 +/- 6.5 mug/l (P < 0.05 vs hypopituitary) for obese and 68.1 +/- 5.5 mug/l (P < 0.05 vs hypopituitary) for normal subjects. Individually considered, after ITT, GHRH or GHRH+Ac, the maximal response in hypopituitary patients was lower than the minimal response in normal but higher than the minimal response in obese subjects. In contrast, after GHRH+GHRP-6 the maximal response in hypopituitary patients was lower than the minimal response in normal and obese subjects. Conclusions: This study suggests that, in this group of patients, although both acipimox and GHRP-6 partially reverse the functional hyposomamotropism of obesity after GHRH, but are unable to reverse the organic hyposomatotropism of hypopituitarism, the combined test GHRH+GHRP-6 most accurately distinguishes both situations, without the side effects of ITT.