Diana Lopez, MD; Miguel Angel Luque-Fernandez, PhD, MPH, MSc; Amy Steele, BA; Gail K. Adler, MD, PhD; Alexander Turchin, MD, MS; Anand Vaidya, MD, MMSc
Note: Drs. Lopez, Luque-Fernandez, and Vaidya had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Support: Dr. Adler was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award K24 HL103845. Dr. Vaidya was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award R01 DK107407; by grant 2015085 from the Doris Duke Charitable Foundation; and by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award K23HL111771.
Disclosures: Dr. Adler reports a grant from the National Institutes of Health during the conduct of the study. Dr. Turchin reports personal fees from Novo Nordisk and Monarch Medical Technologies and grants from Sanofi and Merck outside the submitted work. Dr. Vaidya reports grants from the National Institutes of Health and the Doris Duke Charitable Foundation during the conduct of the study and personal fees from the Endocrine Society 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=M16-0547.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy 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. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol: Described in the text. Statistical code and data set: Available from Dr. Vaidya (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Anand Vaidya, MD, MMSc, Center for Adrenal Disorders, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, RFB 287, Boston, MA 02115; e-mail, email@example.com.
Current Author Addresses: Drs. Lopez, Adler, Turchin, and Vaidya: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, RFB, Boston, MA 02115.
Dr. Luque-Fernandez: Department of Epidemiology and Non-communicable Diseases Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
Ms. Steele: University of California at Davis School of Medicine, 2138 University Park Drive, Sacramento, CA 95825.
Author Contributions: Conception and design: D. Lopez, M.A. Luque-Fernandez, A. Vaidya.
Analysis and interpretation of the data: D. Lopez, M.A. Luque-Fernandez, G.K. Adler, A. Vaidya.
Drafting of the article: D. Lopez, M.A. Luque-Fernandez, G.K. Adler, A. Vaidya.
Critical revision of the article for important intellectual content: D. Lopez, M.A. Luque-Fernandez, A. Turchin, A. Vaidya.
Final approval of the article: D. Lopez, M.A. Luque-Fernandez, A. Steele, G.K. Adler, A. Turchin, A. Vaidya.
Statistical expertise: M.A. Luque-Fernandez, A. Vaidya.
Obtaining of funding: A. Vaidya.
Administrative, technical, or logistic support: A. Steele, A. Vaidya.
Collection and assembly of data: D. Lopez, A. Steele, A. Vaidya.
Lopez D, Luque-Fernandez MA, Steele A, Adler GK, Turchin A, Vaidya A. “Nonfunctional” Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes: A Cohort Study. Ann Intern Med. 2016;165:533-542. doi: 10.7326/M16-0547
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Published: Ann Intern Med. 2016;165(8):533-542.
Published at www.annals.org on 2 August 2016
Benign adrenal tumors are commonly discovered on abdominal imaging. Most are classified as nonfunctional and are considered to pose no health risk, but some are considered functional because they secrete hormones that increase risk for metabolic and cardiovascular diseases.
To evaluate the hypothesis that nonfunctional adrenal tumors (NFATs) increase risk for cardiometabolic outcomes compared with absence of adrenal tumors.
Integrated hospital system.
Participants with benign NFATs (“exposed”; n = 166) and those with no adrenal tumor (“unexposed”; n = 740), with at least 3 years of follow-up.
Medical records were reviewed from the time of abdominal imaging for development of incident outcomes (hypertension, composite diabetes [prediabetes or type 2 diabetes], hyperlipidemia, cardiovascular events, and chronic kidney disease) (mean, 7.7 years). Primary analyses evaluated independent associations between exposure status and incident outcomes by using adjusted generalized linear models. Secondary analyses evaluated relationships between NFATs and cortisol physiology.
Participants with NFATs had significantly higher risk for incident composite diabetes than those without adrenal tumors (30 of 110 [27.3%] vs. 72 of 615 [11.7%] participants; absolute risk, 15.6% [95% CI, 6.9% to 24.3%]; adjusted risk ratio, 1.87 [CI, 1.17 to 2.98]). No significant associations between NFATs and other outcomes were observed. Higher “normal” postdexamethasone cortisol levels (≤50 nmol/L) were associated with larger NFAT size and higher prevalence of type 2 diabetes.
Potential bias in the selection of participants and ascertainment of outcomes.
Participants with NFATs had a significantly higher risk for diabetes than those without adrenal tumors. These results should prompt a reassessment of whether the classification of benign adrenal tumors as “nonfunctional” adequately reflects the continuum of hormone secretion and metabolic risk they may harbor.
National Institutes of Health and Doris Duke Charitable Foundation.
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Adrenal Disorders, Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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