Endocrine Abstracts

Background: Patients with Addison’s disease (AD) and hypopituitarism have increased mortality, mainly from vascular disease. Both diseases are characterised by DHEA(S) deficiency yet this is not usually corrected. It is unclear whether treatment of these conditions with DHEA improves vascular risk.

Objective: To evaluate the effects of DHEA on arterial stiffness and endothelial function in subjects with AD and hypopituitarism.

Methods: Ethical and MHRA approval was obtained for this study of 40 subjects with adrenal insufficiency free of known cardiovascular disease and on full standard hormone replacement (20 AD; 20 hypopituitarism; ISRCT number 46268487). Subjects were assigned to consecutive 12-week treatment periods of DHEA 50 mg or placebo in a randomised, double-blind, crossover design, separated by an 8 week washout. Primary outcome parameters were measures of arterial stiffness (augmentation index (AIx), central blood pressure, brachial and aortic pulse wave velocity (b/aPWV)) and endothelial function. Serum androgens, anthropometry, lipids, HOMA-IR, high sensitivity CRP, adiponectin and plasminogen activator inhibitor-1 were also assessed.

Results: Despite normalisation of DHEAS, androstenedione and testosterone (females), DHEA replacement did not affect AIx, aPWV, central BP or endothelial function. A small increase in the time of travel of the reflected wave (T_R) and reduction in bPWV, both consistent with reduced arterial stiffness in the brachial tree, was observed with DHEA therapy but these did not quite achieve significance (T_R: +3.7 ms, P=0.07, 95% CI for the difference −0.25 to +7.61; bPWV: −0.37 m/s, P=0.07, 95% CI for the difference −0.75 to +0.03). DHEA did not affect any anthropometric/metabolic measures, apart from a small reduction in HDL cholesterol (−0.08 mmol/l, P=0.007, 95% CI for the difference −0.13 to −0.02).

Conclusions: Short-term DHEA supplementation does not improve vascular function in patients with AD or hypopituitarism hence factors other than DHEA(S) deficiency must account for the excess vascular mortality in these conditions.