Cardiometabolic profile and urinary metabolomic alterations in non-functioning adrenal incidentalomas: A review

Background The incidence of adrenal incidentalomas (AIs) has increased over the last 20 years, most of which are apparently non-functioning adrenal adenomas. However, increased evidence supports the existence of an association between non-functioning adrenal incidentalomas (NFAI) and an unfavourable cardio-metabolic profile. Methods This study offers a comprehensive review of the available evidence supporting a higher cardiometabolic risk in NFAIs compared to controls without adrenal tumours. Moreover, it summarises the studies focused on the differential urinary metabolomic profile of NFAI and controls without adrenal lesions. Results This adverse metabolic profile of patients with NFAI includes a higher prevalence of insulin resistance, obesity, hypertension, hyperglycaemia, dyslipidaemia, and cardiovascular alterations and mortality compared to healthy controls without adrenal tumours. Although the pathophysiology that explains the association between NFAI and the parameters of metabolic syndrome and cardiovascular risk is a relatively unexplored field of study, some evidence supports that there are a series of incipient alterations in cortisol metabolism not detected with the classical tests that led to this detrimental profile. These alterations may be potentially detected by a comprehensive metabolomics approach. Several studies detected a shift towards an increase of urinary cortisol metabolites excretion in NFAIs compared to controls without adrenal tumours. Conclusion In view of the higher cardiometabolic risk in NFAI than in controls without adrenal tumours, and the detected alterations in metabolomics profile of NFAI, I propose that the term of NFAI should be changed for another term that best fits to its linked cardiometabolic profile.