Effect of corticoid therapy on growth hormone secretion

Exogenous corticoids are known to be potent inhibitors of linear growth in children. We investigated the mechanisms underlying growth failure by evaluating growth hormone (GH) release during short-term high-dose prednisone treatment (40 mg/m2/day given orally in 3 divided doses) and 7 days after steroid withdrawal in 7 prepubertal children (4 males, 3 females, age range 3-12 years), affected by acute lymphoblastic leukemia. Patients also received weekly administrations of vincristine (1.5 mg/m2 i.v.), daunomycin (20 mg/m2 i.v.) and L-asparaginase (6,000 IU/m2 i.m.). Corticoid therapy suppressed GH secretion during deep sleep as well as in response to arginine, insulin and GH-releasing hormone (GHRH) administration. A significant recovery of GH responsiveness after drug discontinuation was observed during deep sleep (14.03 +/- 3.47 vs. 1.49 +/- 0.43 ng/ml, p < 0.025) as well as in response to arginine (13.63 +/- 2.73 vs. 4.95 +/- 1.54 ng/ml, p < 0.025) and GHRH (32.62 +/- 4.59 vs. 7.27 +/- 3.52 ng/ml, p < 0.005) but not to insulin (7.12 +/- 0.88 vs. 4.47 +/- 0.96 ng/ml, p = NS). Insulin-like growth factor 1 levels during deep sleep (0.61 +/- 0.13 IU/ml/min) were found to be low in the course of steroid therapy and did not increase after drug withdrawal (0.41 +/- 0.07 IU/ml/min). Our preliminary data suggest that recovery of adrenergic response to insulin does not immediately follow corticosteroid discontinuation.