Cardiovascular status in endogenous cortisol excess: the prospective CV-CORT-EX study.

Objective: Cushing´s syndrome (CS) results in increased cardiovascular morbidity and mortality. Subtype-specific differences and possible reversibility after biochemical cure are not well investigated.

Design: Prospective cohort study evaluating the cardiovascular status in different forms of endogenous cortisol excess.

Methods: Patients with overt CS (n=40, 47±13 years, 75% women; 18 pituitary, 13 adrenal, 9 ectopic), biochemically cured CS (n=56, 53±12 years, 79% women; 30 pituitary, 21 adrenal, 5 ectopic), and adrenal incidentalomas with mild autonomous cortisol secretion (MACS) (n=18, 62±11 years, 56% women) underwent comprehensive biochemical, metabolic, and cardiovascular assessment. Results were compared with a representative sample of the general population of Würzburg (n=4965, 55±12 years, 52% women).

Results: Overt CS was associated with left ventricular (LV) remodeling along with hypertrophy and impaired longitudinal systolic/diastolic function at echocardiography. In 20 CS patients followed for a median of 8 (quartiles: 6, 11) months after biochemical remission, hypertension and hyperglycemia were better controlled, while cardiac alterations only partially improved. Patients with previous CS (median time of biochemical remission: 95 (36, 201) months) had worse diastolic function than the general population (LV relaxation velocity e´ 0.08 (0.07, 0.10) ms-1 vs 0.10 (0.08, 0.12) ms-1, p<0.001). In MACS, cardiac remodeling was even more pronounced than in individuals with metabolic syndrome.

Conclusions: In patients with overt CS, cured CS, and MACS, we found a sizable and significant deviation from the general population mean regarding cardiac structure and function. Even mild cortisol excess is associated with glucocorticoid-induced cardiac alterations which appear to persist despite long-term biochemical remission.