Natural History of Adrenal Incidentalomas with and without Mild Autonomous Cortisol Excess A Systematic Review and Meta-analysis

Yasir S. Elhassan, Fares Alahdab, Alessandro Prete, Danae A. Delivanis, Aakanksha Khanna, Larry Prokop, Mohammad H. Murad, Michael W. O'Reilly, Wiebke Arlt, Irina Bancos

Research output: Contribution to journalReview article

5 Scopus citations


Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear. Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality. Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction. Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up. Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality. Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8 months. Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE. Limitation: Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous. Conclusion: During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalAnnals of internal medicine
Issue number2
StatePublished - Jul 16 2019


ASJC Scopus subject areas

  • Internal Medicine

Cite this

Elhassan, Y. S., Alahdab, F., Prete, A., Delivanis, D. A., Khanna, A., Prokop, L., Murad, M. H., O'Reilly, M. W., Arlt, W., & Bancos, I. (2019). Natural History of Adrenal Incidentalomas with and without Mild Autonomous Cortisol Excess A Systematic Review and Meta-analysis. Annals of internal medicine, 171(2), 107-116.