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

Abstract

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), 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., 0 min), GHRH (100 microg, i.v., 0 min), GHRH (100 microg, i.v., 0 min) preceded by acipimox (250 mg, orally, at -270 min and -60 min) (GHRH+Ac); and GHRH (100 microg, i.v., 0 min) plus GHRP-6 (100 microg, i.v., 0 min) (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 microg/l for hypopituitary, 10.1+/-1.7 microg/l (P<0.05 vs hypopituitary) for obese and 17.8+/-2.0 microg/l (P<0.05 vs hypopituitary) for normal. GHRH-induced GH secretion was 2+/-0.7 microg/l for hypopituitary, 3.9+/-1.2 microg/l (P=NS vs hypopituitary) for obese and 22.2+/-3.8 microg/l (P<0.05 vs hypopituitary) for normal. After GHRH+Ac, mean peak GH secretion was 3.3+/-1.4 microg/l for hypopituitary, 14.2+/-2.7 microg/l (P<0.05 vs hypopituitary) for obese and 35.1+/-5.2 microg/l (P<0.05 vs hypopituitary) for normal. GHRH+GHRP-6 induced mean peak GH secretion of 4.1+/-0.9 microg/l for hypopituitary, 38.5+/-6.5 microg/l (P<0.05 vs hypopituitary) for obese and 68.1+/-5.5 microg/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.