Endocrine Abstracts

Background: Subclinical Cushing’s syndrome (SCS) is defined as alterations in hypothalamic–pituitary–adrenal axis without classic signs or symptoms of glucocorticoid excess. It is still controversial whether SCS leads to metabolic and cardiovascular diseases, and if the degree of subclinical hypercortisolism may predict these clinical outcomes.

Aim: To evaluate the prevalence of hypertension, type-2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke, osteoporosis, and osteoporotic fractures, and the relationship of these outcomes to increasing patterns of subclinical hypercortisolism, in patients with adrenal adenomas classified as non-secreting (NSA) and SCS.

Methods: Using the 1-mg dexamethasone suppression test (DST) as primary diagnostic tool, 348 patients were classified as above: 203 were defined NSA and 19 SCS, using the most stringent cut-off values (<50 and >138 nmol/l respectively). Patients with cortisol post-DST between 50 and 138 nmol/l were considered intermediate phenotypes and classified as minor (n=71) and major (n=55) using plasma ACTH and/or urinary free cortisol as additional diagnostic tools.

Results: SCS patients showed higher prevalence of T2D, CHD, osteoporosis, and osteoporotic fractures, respect to NSA. Intermediate phenotypes showed also higher prevalence of CHD and T2D, respect to NSA. The prevalence of all clinical outcomes was not different between intermediate phenotype patients, which were therefore considered as a single group (IP) for multivariate logistic regression analysis. This analysis was performed to evaluate the relationships between potential risk factors (including the cortisol secreting pattern) and the adverse clinical outcomes: both IP and SCS secreting patterns showed a significant association with CHD (odds ratio – OR 4.09; 95% CI 1.47–11.38 and OR 6.10; 95% CI 1.41–26.49 respectively), independently of other potential risk factors. SCS was also independently associated with osteoporosis (OR 5.94; 95% CI 1.79–19.68).

Conclusion: Patterns of increasing subclinical hypercortisolism in adrenal adenomas are associated with increased prevalence of adverse metabolic and cardiovascular outcomes, independently of other potential risk factors.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.