Glucocorticoid replacement therapy: are patients over treated and does it matter?

Background And Objectives: Adequate assessment of patients on glucocorticoid replacement therapy is of great importance to avoid the consequences of under or over treatment, but no simple test is available for this. The aims of this study were (1) to assess adequacy of glucocorticoid replacement in hypoadrenal patients, (2) to correlate serum cortisol levels (cortisol day curve) with 24-hour urine free cortisol excretion and (3) to assess the impact of glucocorticoid dose optimization on markers of bone formation and bone resorption.

Design: Cross-sectional study of current replacement therapy and a prospective study of the effect of dose alteration on bone turnover markers.

Patients: Thirty-two consecutive patients on replacement glucocorticoid therapy (12 Addison's disease, 20 hypopituitarism) from a University teaching hospital out-patient department.

Measurements: Serum and urinary cortisol, osteocalcin, N-telopeptide of type I collagen (NTX) and bone mineral density.

Results: 28/32 (88%) patients required a change of therapy; 24/32 (75%) a total reduction in dose, 18/32 (56%) a change in replacement therapy regimen or drug and 14/32 (44%) both changes. The mean daily dose of hydrocortisone was reduced from 29.5 +/- 1.2 to 20.8 +/- 1.0 mg. A significant correlation was found between peak cortisol and 24-hour urine free cortisol/ creatinine (Spearman correlation r = 0.60, P < 0.0001; n = 51). Following hydrocortisone dose reduction, median osteocalcin increased from 16.7 micrograms/l (range 8.2-65.7) to 19.9 micrograms/l (8.2-56.3); P < 0.01, with no change in the NTX/creatinine ratio.

Conclusions: A high proportion of patients on conventional corticosteroid replacement therapy are over treated or on inappropriate replacement regimens. To reduce the long term risk of osteoporosis, corticosteroid replacement therapy should be individually assessed and over replacement avoided.