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 Corn\l=e'\ 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 Department of Endocrinology. University Hospital Utrecht, The Netherlands; Department of Medical Physiology and Sports Medicine1, Utrecht University, The Netherlands 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\p=n-\6. ISSN 0804\p=n-\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 As a result of the characterization of circulating growth hormone (GH) forms (1), and as an extension of a GH binding protein (GHBP) found in liver cytosol (2), a high-affinity low-capacity protein that specifically binds human GH has been isolated. Soon after the character¬ ization of this GHBP, it appeared that this protein and the extracellular domain of the GH receptor were identical (3). Studies investigating GHBP levels in Laron-type dwarfism (4) and pygmies (5, 6) led to the conclusion that the level of circulating GHBP can be considered to be a measure for the tissue GH receptor concentration. Low GHBP levels were found in patients with active acromegaly (7, 8) and in children with idiopathic GH deficiency (9-11). Treatment of these disorders led to an increase in GHBP levels, suggesting that endogenous GH is a modulator of serum GHBP levels. On the contrary, Martha et al. (12) studied 43 GH-deficient children, and found normal GHBP levels and no influence of GH replacement therapy on GHBP levels. Data regarding GHBP levels in patients with adult-onset GHD are scarce and based on a relatively small number of subjects. Ho et al. (13) and Rajkovic et al. (14) found that the plasma GHBP levels in patients with adult-onset GHD were no different from the controls and did not observe any effect of GH replacement therapy on plasma GHBP levels. Davila et al (15) found also no statistically significant difference in plasma GHBP activity between a GH-deficient group and a control group. Taken together, these results show that the relationship between GH and GHBP is not clear. In this study, we report on the findings in 36 patients with adult-onset GH deficiency, regarding plasma GHBP, insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) levels. Subjects and material Thirty-six patients (22 men and nine premenopausal and five postmenopausal women) with a mean age of 45 years (range 20-60 years), body mass index (BMI)