MON-447 Impact Of Cortisone And Glucocorticoid Metabolites On Bone Turnover Markers in Male Patients With Hypopituitarism

Background: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known on the effect of glucocorticoids on bone remodeling when used as replacement therapy in patients with adrenal insufficiency. Enhanced intracellular conversion of cortisone to active cortisol, by 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism may contribute to a deleterious effect on bone health in this patient group. Study Design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-hour serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-hour urine collection for measurement of urinary corticosteroid metabolites by GC-MS. Serum cortisone and cortisol were analysed by LC-MS/MS. Results: Dose related and circadian variations in serum cortisone were seen to parallel those for cortisol. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20mg/10mg) [670.5 (IQR 621-809.2)] compared to those on dose C (10mg/5mg) [562.8 (IQR 520.1-619.6), p=0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC[1-49] (r=-0.42, p=0.03), and PINP (r=-0.49, p=0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC[1-49] (r= -0.41, p=0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r=-0.39, p=0.04), and OC[1-49] (r=-0.35, p=0.06). Conclusion: Serum cortisone and total urinary total cortisol metabolites are associated with alterations in bone turnover markers suggesting an important role of tissue-specific metabolism of glucocorticoids on bone metabolism in patients receiving HC replacement therapy.