Endocrine Abstracts

Cortisol and cortisone are interconverted by type 1 and type 2 11ßhydroxysteroid dehydrogenase (11ßHSD) isoenzymes. The type 1 isoenzyme is a widely expressed reductase that converts cortisone to cortisol regulating glucocorticoid tissue exposure. Its activity is inhibited by GH and IGF-I, being increased in GH deficiency (GHD) and decreased in acromegaly. In our experience rhGH therapy unmasked a central hypoadrenal state in adults with organic GHD, likely by normalizing 11ßHSD1 activity and reducing cortisone to cortisol conversion.

Aim of this study was to evaluate the hypothalamus-pituitary-adrenal (HPA) axis in 9 children (5M and 4F, mean age 12.0±1.1 (S.E.) yrs, mean height SDS −2.1±0.4) with idiopathic isolated GHD. Measurements were performed at baseline and on rhGH therapy (mean duration: 12±3 months, mean dose: 0.03±0.01 mg/kg bw/day). HPA function was assessed by basal serum cortisol levels and after 1 mcg ACTH test (n=4 patients) or insulin tolerance test (ITT, n=5 patients). Central hypoadrenalism was excluded for both tests by the presence of either a peak of cortisol >500 nmol/L or a cortisol absolute delta >200 nmol/L. Serum IGF-I levels normalized on rhGH. Mean basal serum cortisol levels on rhGH, though showing a slight decrease, did not significantly differ from those recorded at baseline (215±28 vs 256±52 nmol/L, respectively, P=NS). The serum cortisol peak either after 1 mcg ACTH and after ITT was the same on rhGH therapy and at baseline (515±126 vs 574±131 nmol/L, respectively, P=NS). Plasma ACTH levels did not vary significantly. In conclusion, according to the diagnostic criteria, no child became central hypoadrenal on rhGH, contrary to what observed in adult patients with organic GHD and multiple pituitary deficits. This finding further supports the view that only in patients with organic multiple pituitary hormone deficiency GH deficiency may mask the presence of a hidden central hypoadrenalism.