EVIDENCE FOR PARTIAL GROWTH-HORMONE INSENSITIVITY AMONG PATIENTS WITH IDIOPATHIC SHORT STATURE

Objective: To determine whether some patients with idiopathic short stature have partial resistance to growth hormone (GH), Patients with idiopathic short stature have decreased serum levels of the GH receptor-related GH-binding protein (GHBP), and low GHBP levels are associated with complete GH insensitivity (Laron) syndrome, We hypothesized that patients with idiopathic short stature and low GHBP levels may also have a degree of GH insensitivity. Design: Retrospective analysis of patients in a multicenter study. Setting: Ninety-six National Cooperative Growth Study centers in the United States and Canada. Subjects: Five hundred eleven patients with idiopathic short stature who were treated with GH. All patients had a baseline height standard deviation score of less than -2 and a maximum stimulated GH level greater than 10 mu g/L, Of these, 101 (20%) had a baseline GHBP standard deviation score of -2 or less. Results: The patients with low GHBP levels, in comparison with those with normal GHBP levels, had a lower mean extracted standard deviation score for insulin-like growth factor I (-3.3 +/- 1.1 vs -2.5 +/- 1.4; p <0.0001) but higher mean 12-hour GH values (2.8 +/- 1.1 vs 2.3 +/- 1.1 mu g/L; p <0.0001). The differences between groups were statistically significant after control for age and weight-for-height standard deviation score. Among prepubertal patients, there was no significant difference between the low and normal GHBP groups in mean pretreatment or first-year growth rate (p = 0.74, 0.61 respectively) with comparable doses of GH. Conclusions: Patients with idiopathic short stature and low GHBP levels, compared with those with normal GHBP levels, had significantly lower standardized levels of insulin-like growth factor I, and higher mean 12-hour GH levels, which suggest partial GH insensitivity. There was no significant correlation of GHBP levels with the growth response to exogenous GH.