A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency

Abstract

Objective: The international, first-line diagnostic test for adult GH deficiency is the insulin tolerance test (ITT), which is contraindicated in some patients due to severe adverse events. Alternatives such as GH-releasing hormone combined with arginine or GH-releasing peptides (GHRP) have been proposed. We validated the use of GHRP-2 for diagnosing adult GH deficiency (GHD). Methods: Seventy-seven healthy subjects and 58 patients with peak GH<3 μg/l by ITT were enrolled. After overnight fasting, a 100 μg dose of GHRP-2 was administered intravenously; blood samples were taken during the subsequent 2 h and GH measured by immunoradiometric assay. Results: Serum GH peak occurred within 60 min after GHRP-2 administration in all subjects. GH responses to GHRP-2 were not affected by gender, but were slightly lower in elderly subjects and those with adiposity, although these did not influence diagnosis of GHD. Repeated tests showed favourable reproducibility. Peak GH concentrations after GHRP-2 were significantly (P<0.001) lower in patients (1.36±2.60 μg/l) than the healthy group (84.6±60.9 μg/l) with no difference between hypothalamic and pituitary diseases. Serum GH concentration at the point where sensitivity of response crossed with specificity ranged from 15 to 20 μg/l. A cut-off value of 15 μg/l for diagnosing GHD with GHRP-2 corresponded to the diagnostic value of 3 μg/l in the ITT. Conclusions: The GHRP-2 provocative test showed favourable reproducibility and was mildly influenced by age and adiposity. Severe GH deficiency could be diagnosed with high reliability using a 15 μg/l (9 μg/l when GH calibrated with recombinant World Health Organization 98/574 standard) cut-off for peak GH concentration.