TREATMENT OF GLUCOCORTICOID-INDUCED GROWTH SUPPRESSION WITH GROWTH-HORMONE

Growth failure is common during long term treatment with glucocorticoi ds (GC) due to blunting of GH release, insulin-like growth factor I (I GF-I) bioactivity, and collagen synthesis. These effects could theoret ically be reversed with GH therapy. The National Cooperative Growth St udy database (n = 22,005) was searched for children meeting the follow ing criteria: 1) pharmacological treatment with GC and GK for more tha n 12 months, 2) known type and dose of GC, and 3) height measurements for more than 12 months. A total of 83 patients were identified. Monit oring of glucose, insulin, IGF-I, IGF-binding protein-3, type 1 procol lagen, osteocalcin, and glycosylated hemoglobin levels was performed i n a subset of patients. Stimulated endogenous GH levels mere less than 10 mu g/L in 51% of patients and less than 7 mu g/L in 37% of patient s. The mean GC dose, expressed as prednisone equivalents, was 0.5 +/- 0.6 mg/kg.day. Baseline evaluation revealed extreme short stature (mea n height sn score = -3.7 +/- 1.2), delayed skeletal maturation (mean d elay, 3.1 yr), and slowed growth rates (mean, 3.0 +/- 2.5 cm/yr). Afte r 12 months of GH therapy (mean dose, 0.29 mg/kg.weeks), mean growth r ate increased to 6.3 +/- 2.6 cm/yr, and height so score improved by 0. 21 +/- 0.4 (P < 0.01). During the second year of GH therapy (n = 44), the mean growth rate was 6.3 +/- 2.0 cm/yr. Prednisone equivalent dose and growth response to GH therapy were negatively correlated (r = -0. 264; P < 0.05). Plasma concentrations of IGF-I, IGF-binding protein-3, procollagen, osteocalcin, and glycosylated hemoglobin increased with GH therapy, whereas glucose and insulin levels did not change. The fol lowing conclusions were reached. The growth-suppressing effects of GC are counterbalanced by GH therapy; the mean response is a doubling of baseline growth rate. Responsiveness to GH is negatively correlated wi th GC dose. Glycosylated hemoglobin levels increased slightly, but glu cose and insulin levels were not altered by GH therapy.