Six controversial issues on subclinical Cushing’s syndrome

Subclinical Cushing\u2019s syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality. The subclinical Cushing\u2019s syndrome is not rare, being estimated to be between 0.2\u20132 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing\u2019s syndrome screening, diagnosis and treatment. The Altogether to Beat Cushing\u2019s syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing\u2019s syndrome viewpoint regarding the following controversial issues on Subclinical Cushing\u2019s syndrome (SCS): (1) Who has to be screened for subclinical Cushing\u2019s syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushing\u2019s syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushing\u2019s syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushing\u2019s syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushing\u2019s syndrome surgically or conservatively treated? Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing\u2019s syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing\u2019s syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing\u2019s syndrome