Yasir S. Elhassan, MBBS; Fares Alahdab, MD; Alessandro Prete, MD; Danae A. Delivanis, MD, PhD; Aakanksha Khanna, MD; Larry Prokop, MLS; Mohammad H. Murad, MD, MPH; Michael W. O'Reilly, PhD; Wiebke Arlt, MD, DSc; Irina Bancos, MD
Financial Support: By grant 633983 from the European Commission Horizon 2020 program to ENSAT-HT (Dr. Arlt), grant BRC-1215-20009 from the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre (Dr. Arlt), a Clinical Research Fellowship from the MRC Arthritis UK Centre for Musculoskeletal Ageing Research (Dr. Elhassan), Sir George Alberti Research Training Fellowship number 18/0005782 from Diabetes UK (Dr. Prete), a Robert and Elizabeth Strickland Career Development Award (Dr. Bancos), a James A. Ruppe Career Development Award in Endocrinology (Dr. Bancos), and a Catalyst for Advancing in Academics from Mayo Clinic (Dr. Bancos).
Disclosures: Dr. Arlt reports a patent held by University of Birmingham Enterprises about a diagnostic test differentiating benign from malignant adrenal tumors. Dr. Bancos reports advisory board participation with HRA Pharma outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-3630.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: See the Supplement. Statistical code and data set: Available from Dr. Bancos (e-mail, Bancos.Irina@mayo.edu).
Corresponding Author: Irina Bancos, MD, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail, Bancos.firstname.lastname@example.org.
Current Author Addresses: Drs. Elhassan, Prete, and O'Reilly and Prof. Arlt: Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
Drs. Alahdab, Delivanis, Khanna, and Bancos; Mr. Prokop; and Prof. Murad: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Author Contributions: Conception and design: Y.S. Elhassan, A. Prete, M.H. Murad, M.W. O'Reilly, W. Arlt, I. Bancos.
Analysis and interpretation of the data: Y.S. Elhassan, F. Alahdab, A. Prete, M.H. Murad, M.W. O'Reilly, W. Arlt, I. Bancos.
Drafting of the article: Y.S. Elhassan, A. Prete, M.H. Murad, M.W. O'Reilly, W. Arlt, I. Bancos.
Critical revision of the article for important intellectual content: Y.S. Elhassan, F. Alahdab, A. Prete, D.A. Delivanis, L. Prokop, M.H. Murad, W. Arlt, I. Bancos.
Final approval of the article: Y.S. Elhassan, F. Alahdab, A. Prete, D.A. Delivanis, A. Khanna, L. Prokop, M.H. Murad, M.W. O'Reilly, W. Arlt, I. Bancos.
Statistical expertise: F. Alahdab, M.H. Murad.
Obtaining of funding: W. Arlt, I. Bancos.
Administrative, technical, or logistic support: M.H. Murad, I. Bancos.
Collection and assembly of data: Y.S. Elhassan, A. Prete, D.A. Delivanis, A. Khanna, L. Prokop, M.W. O'Reilly, I. Bancos.
Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear.
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.
MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction.
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.
Pairs of reviewers extracted outcomes and assessed methodological quality.
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.
Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous.
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.
Elhassan YS, Alahdab F, Prete A, Delivanis DA, Khanna A, Prokop L, et al. Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis. Ann Intern Med. [Epub ahead of print 25 June 2019]171:107–116. doi: 10.7326/M18-3630
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Published: Ann Intern Med. 2019;171(2):107-116.
Published at www.annals.org on 25 June 2019
Adrenal Disorders, Endocrine and Metabolism, Endocrine Cancer, Hematology/Oncology.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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