Treatment of Glucocorticoid-Induced Growth Suppression with Growth Hormone

Abstract

Growth failure is common during long term treatment with glucocorticoids (GC) due to blunting of GH release, insulin-like growth factor I (IGF-I) bioactivity, and collagen synthesis. These effects could theoretically be reversed with GH therapy. The National Cooperative Growth Study database (n = 22,005) was searched for children meeting the following criteria: 1) pharmacological treatment with GC and GH for more than 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. Monitoring of glucose, insulin, IGF-I, IGF-binding protein-3, type 1 procollagen, osteocalcin, and glycosylated hemoglobin levels was performed in a subset of patients. Stimulated endogenous GH levels were less than 10 microg/L in 51% of patients and less than 7 microg/L in 37% of patients. The mean GC dose, expressed as prednisone equivalents, was 0.5 +/- 0.6 mg/kg day. Baseline evaluation revealed extreme short stature (mean height SD score = -3.7 +/- 1.2), delayed skeletal maturation (mean delay, 3.1 yr), and slowed growth rates (mean, 3.0 +/- 2.5 cm/yr). After 12 months of GH therapy (mean dose, 0.29 mg/kg x weeks), mean growth rate increased to 6.3 +/- 2.6 cm/yr, and height SD 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 following 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 with GC dose. Glycosylated hemoglobin levels increased slightly, but glucose and insulin levels were not altered by GH therapy.

Dexamethasone reduces ATDC5 chondrocyte cell viability by inducing autophagy

“…Although compensatory growth often follows the cessation of GC therapy, children with systemic chronic inflammatory diseases subjected to long-term GC treatment may have reduced final height (14,15). Normalizing height in these children, even with concomitant therapy with high-dose recombinant GH, is not straightforward (16)(17)(18). Moreover, permanent growth impairment has been reported in children receiving alternate-day GC treatment (19,20).…”

Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age

“…This suggests that GR gene polymorphisms do not have a substantial effect on the sensitivity to GH in this group. The growth retarding effect of GCs, known from corticosteroid treatment, is caused by the inhibition of endogenous GH secretion, collagen synthesis, cartilage sulfation, chondrocyte mitosis, GH receptor binding, and insulin-like growth factor 1 activity (33). It should, however, be noted that growth retardation is only seen when supraphysiological doses of corticosteroids are used.…”

IGFs and IGF-binding proteins in short children with steroid-dependent nephrotic syndrome on chronic glucocorticoids: changes with 1 year exogenous GH

“…The recent report from the large National Cooperative Growth Study showed that, whereas there was a general trend in that the higher the glucocorticoid dose the more severe the growth retardation, children on an identical glucocorticoid dose could have growth velocities ranging from 0 to 15 cm/year (22). Such a wide and varying range of growth velocities may be the result of the differing underlying pathologies in the study patients rather than the glucocorticoid dosage.…”