A systematic review and meta-analysis about the prevalence of functioning adrenal incidentalomas

Objective: Adrenal hyperfunction is associated with an increased risk of cardio-metabolic complications in subjects with adrenal incidentaloma. The aim of our study was to assess the prevalence of autonomous/possible autonomous cortisol secretion, primary aldosteronism, pheochromocytoma and Cushing syndrome in patients with adrenal incidentaloma. Design and method: We performed a comprehensive search of multiple databases (PubMed, Ovid MEDLINE, Web of Science) for potentially relevant studies without language restriction, up to February 2022. Studies were excluded if the diagnostic criteria used for diagnosing the hormonal alteration were not available or not in agreement with the available guidelines; in case of duplicate reports or if the studies were performed on selected cohorts of patients/specific populations. Results: We included 36 studies in the final analysis. The overall prevalence of functioning adrenal incidentalomas was 27.5%. Autonomous cortisol secretion/possible autonomous cortisol secretion, with a prevalence of 11.7% (95% C.I. 8.6, 15.7), was the most frequent hormonal alteration, while primary aldosteronism occurred in 4.4% of the patients (95% C.I. 3.1, 6.2). Subgroup analysis showed that primary aldosteronism was more prevalent in patients from Asia compared with patients from Europe/America, on the contrary, autonomous cortisol secretion/possible autonomous cortisol secretion had a lower prevalence in Asian countries. At meta-regression analysis, the prevalence of autonomous cortisol secretion/possible autonomous cortisol secretion was influenced by the proportion of female patients, while the prevalence of primary aldosteronism was positively associated with the proportion of patients with hypertension and the publication year. Finally, pheochromocytoma and Cushing syndrome prevalence were 3.8% (95% C.I. 2.8, 5.0) and 3.1% (95% C.I. 2.3, 4.3), respectively. Conclusions: We confirmed a wide heterogeneity among studies, that was partially explained by the differences in the populations included, such as the female gender and the geographical regions where patients were recruited; moreover, the year of the study publication plays a potential role in the observed effect, thus underlying an increasing awareness of these hormonal alterations in the latest years.