EVIDENCE FOR PARTIAL GROWTH-HORMONE INSENSITIVITY AMONG PATIENTS WITHIDIOPATHIC SHORT STATURE

Objective: To determine whether some patients with idiopathic short st ature have partial resistance to growth hormone (GH), Patients with id iopathic 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 ha ve a degree of GH insensitivity. Design: Retrospective analysis of pat ients 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 o f -2 or less. Results: The patients with low GHBP levels, in compariso n with those with normal GHBP levels, had a lower mean extracted stand ard 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 we re statistically significant after control for age and weight-for-heig ht 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) w ith comparable doses of GH. Conclusions: Patients with idiopathic shor t stature and low GHBP levels, compared with those with normal GHBP le vels, had significantly lower standardized levels of insulin-like grow th 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.