The GHRH/GHRP-6 test for the diagnosis of GH deficiency in elderly or severely obese men

Objective and design: Ageing and obesity result in decreased activity of the GH/IGF-I axis and concomitant impaired GH responses to secretory stimuli. We therefore determined the validity of the GH cut-off value of 15.0mg/l in the GH-releasing hormone (GHRH)/GH releasing peptide-6 (GHRP-6) test for the diagnosis of GH deficiency in elderly or severely obese men. Methods: We performed a combined GHRH/GHRP-6 test in ten elderly men (mean age 74 years; mean body mass index (BMI) 24.6 kg/m 2 ), nine obese men (mean age 47 years; mean BMI 40.6 kg/m 2 ) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m 2 ). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100mg) and GHRP-6 (93mg) were given intravenously as a bolus injection. Repeated GH measurements were performed for two hours. Results: Both peak GH levels and areas under the curve (AUC) were significantly lower in the obese than in the controls (peak 13.2 vs 53.4mg/l, P ¼ 0.001; AUC 707 vs 3250mg/l £ 120 min; P ¼ 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0mg/l; AUC 2274mg/l £ 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0mg/l associated with severe GH deficiency. All others had GH peak levels exceeding this threshold. IGFBP-3 levels were significantly lower in the elderly than in the controls (1.35 vs 2.05 mg/l, P ¼ 0.001). Baseline GH or IGF-I did not differ significantly between groups. Conclusions: GH responses following GHRH/GHRP-6 administration were significantly reduced in severely obese men, but were not significantly reduced in elderly men, despite a negative trend. Our data indicate that the cut-off GH level of 15.0mg/l after GHRH þ GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.