Increased risks for mortality and cardiovascular disease in primary and secondary adrenal insufficiency, and pituitary disorders have been inconsistently reported. Risk estimations have traditionally used national statistics as reference, with no matching for precise age, and time and place of clinical care of the patients and the reference population. This study evaluated risks for mortality and cardiovascular disease in patients with adrenal insufficiency of any type and, separately, primary and secondary adrenal insufficiency, by comparing with controls individually matched for sex, age, and time and place of care, using as the source of data a UK primary care database (Clinical Practice Research Datalink, CPRD). Additionally, established cardiovascular risk factors were taken into account.
The risk for mortality was increased in patients with adrenal insufficiency (HR, 1.68 [95% CI, 1.58-1.77]) including primary (HR, 1.83 [1.66-2.02]) and secondary adrenal insufficiency (HR, 1.52 [1.40-1.64]). From the first year, the mortality risk was significantly increased, in accordance with an early increase in hospitalisations from adrenal crisis. Cardiovascular disease was the leading cause of death but infections posed the greatest relative mortality risk. Risk for cardiovascular events was increased but was dependent on the presence of cardiovascular risk factors (unadjusted HR, 1.28 [1.20-1.36]; adjusted HR, 1.07 [1.01-1.14]). However, specifically for cerebrovascular disease in secondary adrenal insufficiency, risk was independently increased. Concomitant cardiovascular disease was associated with adrenal crisis-related death.
In conclusion, infections and adrenal crisis could account for the increased risk for mortality in adrenal insufficiency observed at the beginning of disease course. The risk for cardiovascular disease was also increased and could further contribute to adrenal crisis-related mortality. The interaction of the three factors: adrenal crisis, infections and cardiovascular disease, probably plays a part in the increased mortality of patients with adrenal insufficiency.