Endocrine Abstracts

Context: Cushing’s disease (CD) is rare condition burdened by several systemic complications that in turn increase mortality. The main goal of CD treatment is to promptly reduce cortisol excess, but whether remission can revert cortisol-related complications and guarantee a normal life expectancy remains debated.

Aim: To assess the prevalence of cortisol-related complications and mortality in a large monocentric cohort of CD patients followed at our centre.

Materials and methods: We reviewed clinical charts of patients with CD diagnosed between December 2001 and December 2021. Biochemical features, CD treatments history, comorbidities and deaths were recorded.

Results: 126 CD patients, with a median follow-up of 10 years were included. Median age at diagnosis was 39 years, with a prevalence of females gender (F:M=3:1), microadenomas (80.5%) and mild to moderate cortisol excess (77.5%). At last follow-up, 78/126 (61.9%) patients were in remission irrespective of previous treatment strategies. All but one patients with active CD at last follow-up were on medical treatment, achieving normalization of urinary free cortisol and circadian rhythm in about 75% and 25%, respectively. Remission proved a significant improvement in all cardiovascular (CV) comorbidities (P<0.05). Patients presenting multiple comorbidities (at least 3) at last follow-up had increased CV complications (P=0.013). CV events were also more frequent in older patients (P=0.003), smokers (P=0.02) and in persistent cases (P=0.044). Most of thromboembolic (TE) and infective events occurred during active disease. Older age (P=0.04) and dis-glycaemia (P=0.035) were related to TE events; whereas no predictors of infective complications were identified. CV events were the most frequent cause of death. SMR was increased in patients with persistent disease at last follow-up (SMR 4.99, 95%CI [2.15; 9.83], P<0.001), whilst it returns comparable to that of general population after remission (SMR 1.66, 95%CI [0.34; 4.85], P=0.543). This latter finding was confirmed irrespective of timing and number of treatments performed to achieve remission. Younger age at diagnosis (P=0.005), a microadenoma at first imaging (P=0.002) and remission status at last follow-up (P=0.027) increased survival. Conversely, an elevated number of CV risk factors at last follow-up (P=0.0057), especially arterial hypertension, increased mortality.

Conclusions: active CD patients present a poor survival outcome, but disease remission can restore life expectancy. This result seems independent of timing and modalities used to achieve remission. Nevertheless, adequate monitoring and management of persisting CD-related comorbidities is of the outmost importance to reduce both CV events and mortality