Prevalence of functioning adrenal incidentalomas: a systematic review and meta-analysis.

CONTEXT: Adrenal hyperfunction is associated with an increased risk of cardio-metabolic complications in subjects with adrenal incidentaloma (AI). Reliable prevalence estimates of functioning AIs are important to direct resources allocations. OBJECTIVE: To assess the prevalence of autonomous/possible autonomous cortisol secretion (ACS), primary aldosteronism (PA), pheochromocytoma (PHEO) and Cushing syndrome (CS) in patients with AI. DATA SOURCES: 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. STUDY SELECTION: Of the 1,661 publications evaluated at title and abstract levels, 161 were examined as full text and 36 were included. DATA EXTRACTION: Study level clinical data were extracted by three independent reviewers. DATA SYNTHESIS: The overall prevalence of functioning AIs was 27.5% (95% C.I., 23.0, 32.5). ACS/possible ACS, with a prevalence of 11.7% (95% C.I. 8.6, 15.7), was the most frequent hormonal alteration, while PA occurred in 4.4% of the patients (95% C.I. 3.1, 6.2). Subgroup analysis showed that PA was more prevalent in patients from Asia compared with patients from Europe/America, on the contrary, ACS/possible ACS had a lower prevalence in Asian countries. At meta-regression analysis, the prevalence of ACS/possible ACS was influenced by the proportion of female patients, while the prevalence of PA was positively associated with the proportion of patients with hypertension and the publication year. Finally, PHEO and CS prevalence were 3.8% (95% C.I. 2.8, 5.0) and 3.1% (95% C.I. 2.3, 4.3) respectively. CONCLUSIONS: This meta-analysis provides extensive data on the prevalence of functioning AIs and the factors affecting heterogeneity in prevalence estimates.