Empiric Determination of the Daily Glucocorticoid Replacement Dose in Adrenal Insufficiency

For the treatment of adrenal insufficiency (AI) in adults, the Endocrine Society's recommended daily glucocorticoid replacement dose (DGRD) is 15 to 25 mg hydrocortisone (HC), which is approximately 1.7 times the reported mean daily cortisol production rate. Prolonged glucocorticoid overtreatment causes multiple morbidities.

We tested the hypotheses that the DGRD, empirically determined by individual patient titration, is lower than that of the Endocrine Society guidelines and tolerated without evidence of glucocorticoid under-replacement.

We empirically determined the DGRD in 25 otherwise healthy adults with AI by titrating the DGRD to the lowest dose tolerated as judged by body mass index, blood pressure, serum sodium concentration and AI symptoms. Patients received either HC or prednisone (PRED). The HC equivalent of PRED was assumed to be 4:1.

The mean empirically determined DGRD, expressed as HC equivalent, was significantly less than the midpoint of the Endocrine Society's recommended DGRD (7.6 ± 3.5 mg/m² vs 11.8 mg/m²; P < 0.001). The DGRD in the adrenalectomy group was not significantly different than the DGRD of those with other AI causes (7.9 ± 4.0 mg/m² vs 7.3 ± 3.1 mg/m²; P = ns), demonstrating that the empirically determined DGRD was not biased by residual cortisol secretion. There was no evidence of glucocorticoid under-replacement as determined by measured biometrics and AI symptoms.

We conclude that an empirically determined DGRD is significantly lower than that of the Endocrine Society guidelines and tolerated without evidence of glucocorticoid under-replacement.