REVERSAL OF GLUCOCORTICOID-INDUCED GROWTH FAILURE BY HUMAN GROWTH HORMONE(hGH). † 488

Abstract

Growth failure is common during long-term treatment with glucocorticoids(GC) due to blunting of GH release, IGF-1 bioactivity, and collagen synthesis. These effects could theoretically be reversed with hGH therapy. The National Cooperative Growth Study data base (n=22,005) was searched for children meeting the following criteria: 1) pharmacologic treatment with GC and hGH≥ 12mo; 2) known type and dose of GC; 3) height measurements for ≥ 12 mo. A total of 83 patients (ALL) were identified; 45 transplant (T) recipients, 18 with inflammatory (1) diseases, 16 with reactive airway disease(A), and 4 others. Stimulated endogenous GH levels were <10ng/ml in 51% and<7ng/ml in 37% of patients. Average GC dose (prednisone equivalent; P), baseline height (bH-SDS) and growth rate (bGV), and height (deltaH-SDS) and GV(GH-GV) following 12 months of GH therapy (mean dose 0.3mg/kg/wk) were analyzed (mean+SD) for all GC-dependent patients and for each subgroup.(+=based on n=68;*= p<0.01) Table For the total group, there was a (p<0.05) negative correlation between P equivalent dose and growth response to hGH. We conclude that growth suppressing effects of GC are variably counterbalanced by hGH therapy over 12mo. The mean response is a doubling of baseline GV. Responsiveness to GH is inversely correlated with GC dose and severity, but not type, of GC-dependent disease. Possible adverse events (e.g. glucose intolerance, worsening autoimmune disease or transplant function) are being monitored and analyzed in detail. This study was funded by Genentech, Inc.