THE EFFECTS OF GLUCOCORTICOID REPLACEMENT THERAPY ON GROWTH, BONE-MINERAL DENSITY, AND BONE TURNOVER MARKERS IN CHILDREN WITH CONGENITAL ADRENAL-HYPERPLASIA

Even with current so called physiologic doses of glucocorticoid replac ement therapy, children with congenital adrenal hyperplasia (CAH) ofte n show relative short stature and delayed bone maturation, an observat ion that suggests possible long-term effects on bone metabolism of dai ly transient post-absorptive hypercortisolemia. In 28 patients with 21 -hydroxylase or 17 alpha-hydroxylase deficiency (16 females and 12 mal es, ages 4.9-22 yr) who had received oral cortisol 10-15 mg/M-2/day fo r 4.7-22 yr, we studied cortisol bioavailability, growth, bone maturat ion, vertebral bone mineral density, and various markers of bone forma tion and resorption. Patients were grouped according to mean on-therap y serum 170H-progesterone or progesterone levels as tight control (170 HP < 10 nmol/L), fair control (170HP 10-40 nmol/L or progesterone 1.0- 1.5 nmol/L), or poor control (170HP > 40 nmol/L). There was no differe nce in peak postabsorptive serum cortisol or area under the concentrat ion-time curve, and only three patients had a peak serum cortisol of m ore than 700 nmol/L. There was no difference in present height Z-score (-0.96; -0.24; -0.6), height Z-score at age 2 yr (-1.5; +0.4; -1.3), or current growth velocity Z-score (-0.1; +1.2; -2.2) between the grou ps, but bone maturation Z-score was significantly delayed (-1.63) in t he tight control group and advanced (+0.8)in the poor control group. P resent height was highly correlated (r = 0.8) with height at age 2 yr. Serum calcium, phosphorus, alkaline phosphatase, parathormone, and 25 OH-vitamin D levels were all normal. There was no difference between t he groups in age-corrected vertebral bone mineral density, and no diff erence in serum osteocalcin, procollagen peptide, or collagen C-termin al telopeptide, nor in urinary amino-terminal telopeptide. The data su ggest that current methods of cortisol replacement do not-significantl y influence bone formation, resorption or density during childhood and therefore should not contribute to adult osteoporosis. The possibilit y remains that hypercortisolemia during in fancy produces the short st ature and delayed bone maturation that are present by the age 2 yr.