Mortality in Cushing's syndrome: systematic analysis of a large series with prolonged follow-up

Abstract

Objective: In this study, we aim to assess the long-term survival and causes of death in a retrospective cohort study on patients with all aetiologies of endogenous Cushing's syndrome (CS) (except adrenal cancer), presenting to two large tertiary endocrine referral centres, and to identify variables predicting mortality. Results: In total, 418 subjects were identified (311 with Cushing's disease (CD), 74 with adrenal Cushing's (AC) and 33 with ectopic Cushing's (EC)). In CD, the probability of 10-year survival was 95.3% with 71.4% of the deaths attributed to cardiovascular causes or infection/sepsis. SMRs were significantly high overall (SMR 9.3; 95% CI, 6.2-13.4, P!0.001), as well as in all subgroups of patients irrespective of their remission status. In AC, the probability of 10-year survival was 95.5% and the SMR was 5.3 (95% CI, 0.3-26.0) with PZ0.2. Patients with EC had the worst outcome with 77.6% probability of 5-year survival. Conclusions: In this large series of patients with CS and long-term follow-up, we report that in CD the mortality is significantly affected, even after apparently successful treatment. The SMR of patients with AC was high, but this was not statistically significant. The implicated pathophysiological mechanisms for these findings need to be further elucidated aiming to improve the long-term outcome.

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

“…Cushing syndrome (CS) is a clinical state of prolonged exposure to inappropriately high levels of exogenous or endogenous glucocorticoids and is associated with significant morbidity and mortality (1)(2)(3)(4)(5). Surgical resection of the causal tumor(s) remains the first-line therapy for endogenous CS.…”

A critical reappraisal of bilateral adrenalectomy for ACTH-dependent Cushing's syndrome

“…These patients typically suffer from ectopic Cushing's syndrome. They might develop, in addition to classical Cushing's stigmata, life-threatening complications of hypercortisolism, such as bacteraemia and sepsis (27,28,29), thromboembolic complications, intractable hypokalaemic hypertension, heart failure, gastrointestinal haemorrhage, psychosis, debilitating myopathy, uncontrolled hyperglycaemia or a combination of these conditions (30). Serum cortisol levels generally reach 41 mg/dl (1100 nmol/l) and may be even higher than 100 mg/dl (2700 nmol/l).…”

The degree of urinary hypercortisolism is not correlated with the severity of cushing’s syndrome

“…Patients with persistent or recurrent disease show a dramatically increased mortality compared to the general population, while patients who obtain the surgical remission seem to have a mortality rate similar to that of general population, even though some discrepancies have been reported [13]. Indeed, different retrospective studies reported a maintained increased mortality compared to general population, even in patients who achieved the remission [14][15][16], due to the persistence of several comorbidities and strongly dependent on the duration of exposure to glucocorticoid excess.…”