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CLINICAL STUDY |
1 Department of Clinical Endocrinology, University Medical Centre, Utrecht, 2 Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands, 3 Department of Sports Medicine, 4 Laboratory for Endocrinology, University Medical Centre, Utrecht, The Netherlands and 5 Department of Medical Physiology, University of Santiago de Compostela, Santiago de Compostela, Spain
(Correspondence should be addressed to P Sytze van Dam, Department of Internal Medicine, Onze Lieve Vrouwe Gasthuis, PO Box 95 500, 1090HM Amsterdam, The Netherlands; Email: p.s.vandam{at}olvg.nl)
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 15.0 µg/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/m2), nine obese men (mean age 47 years; mean BMI 40.6 kg/m2) and seven healthy male controls (mean age 51 years, mean BMI 24.3 kg/m2). After assessment of fasting plasma GH, IGF-I and IGF-binding protein-3 (IGFBP-3), GHRH (100 µg) and GHRP-6 (93 µg) 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 53.4 µg/l, P = 0.001; AUC 707 vs 3250 µg/l x 120 min; P = 0.001). Mean GH response in the elderly was lower than in the controls (peak 35.0 µg/l; AUC 2274 µg/l x 120 min), but this was not statistically significant. In contrast, GH peak levels in seven obese men remained below the cut-off level of 15.0 µg/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 = 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 15.0 µg/l after GHRH + GHRP-6 administration for the diagnosis of severe GH deficiency cannot be used in severely obese men.
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