# European survey on metabolic and cardiovascular risk in Cushing syndrome

## TL;DR

This survey explores how European experts manage metabolic and cardiovascular risks in Cushing syndrome patients, highlighting practice variations and the need for specific guidelines.

## Contribution

The study provides insights into current practices and gaps in managing cardiovascular risks in Cushing syndrome across European reference centers.

## Key findings

- Most experts consider Cushing syndrome patients at high cardiovascular risk regardless of remission status.
- There is significant variation in the use of provocative testing for diabetes and approaches to dyslipidaemia and overweight.
- Screening for asymptomatic vascular disease is not consistently performed across centers.

## Abstract

Cushing’s syndrome (CS) is associated with increased metabolic and cardiovascular (CV) risk factors and morbidities. Evidence-based guidelines for the management of these issues in active or remitted CS are not available, so best practice is derived from guidelines developed for the general population. We aimed to evaluate the awareness and practice variation for CV comorbidities of CS across Reference Centres (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN).

A dedicated online survey was distributed from June 2022 to December 2022 to Endo-ERN RCs with recognized expertise in adrenal and/or pituitary diseases.

19 centres provided complete responses to the survey, accounting for an estimated pool of around one thousand chronically cared CS patients across Europe. Most ERN experts consider patients with CS at high CV risk irrespectively of remission status. Preoperative cortisol-lowering treatment was a common practice, especially for severe cases, and deemed effective in reducing CV risk by many. Most comorbidities were regularly evaluated at diagnosis and during follow-up, although a lack of provocative testing to diagnose diabetes (used only in 26% of RCs) was evidenced. A strict glycaemic control was encouraged although its target differed. On the contrary, a less stringent approach to dyslipidaemia and overweight emerged. Preferred initial compounds for patients presenting comorbidities were angiotensin converting enzyme inhibitors, metformin and statins; lifestyle changes were preferred over drugs to control weight excess after cure. Screening for asymptomatic vascular disease was performed routinely and regularly repeated during follow-up by only half of the centres. Important heterogeneity in some responses emerged, especially regarding the effect of remission or medical treatment on comorbidities and CV risk.

Our survey highlights the awareness of ERN experts on management of metabolic and CV risk factors or disease in CS. Most of them use the current European guidelines and apply strategies for high CV risk patients, although not all these recommendations were fully followed. Since several CV risk factors seem to persist after disease remission, they should be adequately and promptly addressed. Population-specific studies are required to identify the optimal management of CV and metabolic comorbidities of CS patients.

The online version contains supplementary material available at 10.1007/s40618-025-02663-9.