Abstract
BackgroundDespite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, primary adrenal insufficiency (AI) is associated with an increased mortality, mainly due to cardiovascular disease. The role of MC replacement is not known. Therefore, we assessed whether renin concentrations during routine GC and MC substitution therapy are associated with heart function and morphology.MethodsThirty two patients with primary AI were included in a cross-sectional case–control study. In total, 17 patients and 34 healthy controls (age: 48 ± 12 vs. 46 ± 18 years; BMI: 23 ± 3 vs. 24 ± 3 kg/m2) underwent magnetic resonance spectroscopy and imaging measurements to assess cardiac function, morphology, ectopic lipids, and visceral/subcutaneous fat mass. Patients were divided according to their actual plasma renin concentration at the study visit (Actual-Reninlow vs. Actual-Reninhigh) and their median plasma renin concentration of previous visits (Median-Reninlow vs. Median-Reninhigh).ResultsEjection fraction was higher (67 ± 5 vs. 55 ± 3%; p = 0.001) and left ventricular mass was lower (60 ± 9 vs. 73 ± 10 g/m2; p = 0.025) in Actual-Reninhigh. Median-Reninhigh was associated with lower cardiac mass (64 ± 9 vs. 76 ± 11 g/m2; p = 0.029). Blood pressure, glucose, and lipid metabolism, as well as ectopic lipid content, pericardial fat mass, and visceral/subcutaneous fat were not different between the groups. Compared with controls, ejection fraction was significantly lower in patients with AI (56 ± 4 vs. 63 ± 8%; p = 0.019). No differences were found in patients with ≤20 mg compared with >20 mg of hydrocortisone per day.ConclusionsHigher renin concentrations are associated with more favorable cardiac function and morphology in patients with primary AI.
Highlights
Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, primary adrenal insufficiency (AI) is associated with an increased mortality, mainly due to cardiovascular disease
In contrast to reports of retrospective cohort studies indicating that regular GC and MC substitution therapy might normalize life expectancy, with excess mortality only in patients diagnosed at a younger age [2], other evidence hints at a more than twofold increase in mortality in affected patients compared with the general population, mainly due to increased risk of cardiovascular disease [3, 4]
All patients were on stable GC replacement therapy and 30 patients were on stable MC
Summary
Despite adequate glucocorticoid (GC) and mineralocorticoid (MC) replacement therapy, primary adrenal insufficiency (AI) is associated with an increased mortality, mainly due to cardiovascular disease. In contrast to reports of retrospective cohort studies indicating that regular GC and MC substitution therapy might normalize life expectancy, with excess mortality only in patients diagnosed at a younger age [2], other evidence hints at a more than twofold increase in mortality in affected patients compared with the general population, mainly due to increased risk of cardiovascular disease [3, 4]. In contrast to conventional therapy, when GC is administered two to three times daily to mimic the physiological cortisol rhythm, studies investigating modified-release preparations of hydrocortisone report significant improvements in body mass index (BMI), glucose, and lipid metabolism [6, 7]
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