Endocrine Abstracts

Subclinical Cushing’s syndrome, defined as evidence of alterations of the HPA axis in patients without stigmata of hypercortisolism, is a frequent finding among patients with adrenal incidentalomas. It is well-known that this condition is associated with several co-morbidities, such as hypertension in 2/3 of the cases, diabetes in 1/3, and dyslipidemia, which impair the cardiovascular risk profile of those patients. Recently, different independent reports on the natural history of subclinical hypercortisolism have highlighted an association of this disease with severe cardiovascular outcomes. Specifically, during a long-term follow-up surveillance period, patients with subclinical hypercortisolism show an increased incidence of cardiovascular events, mainly coronary heart disease and stroke, with respect to patients with non-functioning adrenal incidentalomas. Interestingly, an even higher risk of cardiovascular diseases was reported in patients with increased cortisol secretion during follow-up. Moreover, patients with subclinical hypercortisolism also have a reduced survival rate than those with non-functioning tumors, mainly due to cardiovascular events and infectious complications. Increased cortisol levels were independently associated to the increased cardiovascular events and mortality of those patients. It is clear that the hypercortisolism driven by these tumors, although of mild entity, plays a pivotal role in contributing to the worsened cardiovascular profile, when sustained and prolonged for several years. However, although all these data together do not provide enough evidence that the surgical treatment is the best therapeutic option for all patients with subclinical hypercortisolism, they give clues on the existence of different subtypes of diseases that must be better stratified according to the cardiovascular risk and assigned to different follow-up strategies. In this context, randomized trials focused on the efficacy of surgery on cardiovascular outcomes, on one side, and pre-operative steroid profiling with mass spectrometry, on the other side, will be extremely useful in achieving a sub-classification of patients with subclinical hypercortisolism that could benefit from either medical or surgical treatment.