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Corné A Roelen, Hans P Koppeschaar, Wouter R de Vries, Pierre M Zelissen, Yvonne E Snel, Manorath E Doerga, Jos H Thijssen and Rien A Blankenstein

Roelen CA, Koppeschaar HP, de Vries WR, Zelissen PM, Snel YE, Doerga ME, Thijssen JH, Blankenstein RA. High-affinity growth hormone binding protein, insulin-like growth factor I and insulin-like growth factor binding protein 3 in adults with growth hormone deficiency. Eur J Endocrinol 1996;135:82–6. ISSN 0804–4643

The high-affinity growth hormone binding protein (GHBP) circulates in human blood and represents the extracellular domain of the growth hormone (GH) receptor. The effects of GH deficiency on GHBP in adults are not clear. The aim of this study was to evaluate serum GHBP levels in adults with GH deficiency and to assess whether GHBP measurement may contribute to the diagnosis of adult GH deficiency, based on a two-step model. We measured insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3) and GHBP levels in serum samples of 36 patients with adult-onset GH deficiency. The GHBP levels were measured by FPLC size-exclusion chromatography; IGF-I and IGFBP-3 levels were measured by RIA. Serum GHBP levels were elevated above the upper limit of the 95% confidence interval in 26 patients, whereas IGF-I and IGFBP-3 levels were low in 10 patients and in 16 patients, respectively. The combination of low serum IGF-I and low IGFBP-3 levels was found in 10 patients. In nine patients, serum IGF-I levels were low, with elevated GHBP levels. Low serum IGF-I, low IGFBP-3 and elevated GHBP levels were found in five patients. Only four out of 36 patients had serum IGF-I, IGFBP-3 and GHBP levels that were within the 95% confidence interval of the control values. We conclude that adults with acquired GH deficiency have elevated GHBP levels in comparison to healthy subjects. We suggest that measurement of GHBP levels might contribute to the diagnosis of adult GH deficiency, though further research is required to study the additional value of GHBP measurements.

HPF Koppeschaar, Department of Endocrinology, University Hospital Utrecht, HPL00.407, PO Box 85500, 3508 GA Utrecht, The Netherlands

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Sander V Haijma, P Sytze van Dam, Wouter R de Vries, Inge Maitimu-Smeele, Carlos Dieguez, Felipe F Casanueva and Hans P F Koppeschaar

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 × 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 × 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.