Daily Glucocorticoid Replacement Dose in Adrenal Insufficiency, a Mini Review.

The Endocrine Society Guidelines and recent reviews of adrenal insufficiency (AI) recommend a daily glucocorticoid replacement dose of 15 to 25 mg with a midpoint of 20 mg of hydrocortisone (HC) (alternatively 3 to 5 mg prednisolone) in divided doses in otherwise healthy individuals with AI. In contrast, a daily glucocorticoid replacement dose of 4.3 to 26 mg/d HC with a midpoint of 15 mg/d is predicted from current measurements of daily cortisol production rates and oral HC bioavailability. The higher HC doses recommended in the current guidelines may result in glucocorticoid overtreatment of some AI patients and associated long-term adverse outcomes. A titration method for determination of the individual patient's daily glucocorticoid replacement dose and the impact of lower doses are reviewed. Future related research questions are identified.

Empiric Determination of the Daily Glucocorticoid Replacement Dose in Adrenal Insufficiency.

BACKGROUND: 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. HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adrenal vein sampling with and without cosyntropin stimulation for detection of surgically remediable aldosteronism.

CONTEXT AND OBJECTIVE: Bilateral adrenal vein sampling (AVS), the diagnostic standard for identifying surgically remediable aldosteronism (SRA), is commonly performed after cosyntropin stimulation (post-ACTHstim). The role of AVS without cosyntropin stimulation (pre-ACTHstim) has not been established. The selectivity index (SI), the adrenal vein (av) serum cortisol concentration divided by that in a peripheral vein, confirms av sampling. The minimally acceptable SI is controversial. The objectives of this study were to determine the role of pre-ACTHstim AVS and a predetermined SI. DESIGN: Using biochemical cure as the endpoint, we performed a retrospective head-to-head comparison of pre-ACTHstim AVS to post-ACTHstim AVS. The specificity of a predetermined minimum SI of 1.5 in pre-ACTHstim AVS was determined. PATIENTS: At a regional AVS referral centre, we analysed 32 patients who had undergone simultaneous bilateral AVS both pre- and post-ACTHstim and had returned for postadrenalectomy evaluation. MEASUREMENTS: Simultaneous bilateral AVS was performed with measurements of venous concentrations of aldosterone and cortisol. End points were postadrenalectomy plasma renin activity, serum aldosterone concentration, and number of antihypertensive medications. RESULTS: All 32 patients achieved a biochemical cure following adrenalectomy. The two AVS protocols were complementary. Notably, seven patients (22%; CI = 11-38) were found to have SRA by a lateralization index (LI) > 4 on the pre-ACTHstim AVS, but not on the post-ACTHstim AVS. SI pre-ACTHstim was divided into tertiles. Specificity was 100% in all. CONCLUSIONS: Simultaneous bilateral AVS performed both pre-ACTHstim and post-ACTHstim maximizes SRA identification. A SI of 1.5 pre-ACTHstim does not reduce specificity.