SAT-020 Empiric Determination of Daily Glucocorticoid Replacement Doses in Adrenal Insufficiency

Background: The Endocrine Society’s recommended adult daily glucocorticoid replacement dose (DGRD) for adrenal insufficiency (AI) is 15-25 mg cortisol/d. Adjusted for body surface area (BSA), the midpoint is 11.1 mg cortisol/m(2)/d. This is 1.6 times the reported mean daily cortisol production rate (FPR) of 7.0 mg/m(2)/d (range = 2.7-14). Prolonged glucocorticoid over-treatment may cause osteoporosis, diabetes, hypertension and immune suppression. Hypothesis. We tested the hypothesis that a carefully titrated DGRD would approximate the reported FPR without clinically adverse effects. Methods: We empirically determined the DGRD in 22 otherwise healthy adults with AI (17 primary, 5 secondary; 16 women, 6 men) by titrating the DGRD to the lowest dose tolerated as judged by BMI, BP, serum sodium concentration and AI symptoms. Patients received either hydrocortisone (HC) or prednisone. The HC equivalence of prednisone was assumed to be 4 to 1. P < 0.01 was considered statistically significant. BSA was calculated by the Mosteller formula and the Schlich formula that accounts for gender. Results. The DGRD (mean ± SD), expressed as HC equivalent dose and adjusted for BSA (Mosteller formula), was 7.6 ± 3.7 mg/m(2)/d (range 2.0-14.3). This closely approximated the reported mean FPR of 7.0 mg/m(2)/d, and was significantly (p < 0.01) less than the midpoint of the Endocrine Society’s recommended DGRD (11.1 mg/m(2)/d). As with the reported FPR there was a trend of DGRD/BSA to correlate with age (r(2) = 0.20; p = 0.03). To be certain that the DGRD was not biased by residual cortisol secretion, we compared the DGRD in the 11 patients who had undergone bilateral adrenalectomy to those with other AI causes. The DGRD in the adrenalectomy group was 7.8 ± 4.2 mg/m(2)/d and was not significantly different than the DGRD of those with other AI causes (7.4 ± 3.3 mg/m(2)/d). We looked for evidence of over and under replacement by examining the correlation DGRD with BMI, BP, and serum sodium concentration. There were no significant positive correlations. Five patients had minimal hyponatremia with the lowest value being 135 mmol/L (lower nl limit = 137 mmol/L). There was a significant negative correlation of BMI with DGRD/BSA (r(2) = 0.33; p = 0.005), indicating that obesity was not caused by over replacement, and that individuals with endogenous obesity maintained an elevated BMI on a low DGRD. When using the Schlich BSA formula to account for gender, no statistical differences or correlations were altered. Summary: The empirically determined DGRD closely approximated the reported FPR, was significantly lower than the currently recommended DGRD, and was without adverse side effects. Conclusion. A DGRD that is equivalent to FPR, but lower than the Endocrine Society’s DGRD, is adequate for most otherwise healthy patients with AI.