{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T12:30:29Z","timestamp":1791721829754,"version":"4.3.4"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:sec id=\"ab-ioi230038-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>It is unclear if nonfunctional adrenal adenomas (NFAAs) are associated with increased mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi230038-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To analyze mortality and causes of death in patients with NFAA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi230038-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>A national retrospective register-based case-control study was conducted and included 17\u202f726 patients with a diagnosis of adrenal adenoma in Sweden from 2005 to 2019 who were identified and followed up until death or 2020 as well as 124\u202f366 controls without adrenal adenoma. Individuals with diagnoses indicating adrenal hormonal excess or cancer were excluded. Follow-up started after 3 months of cancer-free survival following the date of the NFAA diagnosis. Sensitivity analyses were performed in subgroups of individuals for whom it was assumed that controls would also have undergone computed tomography: those with acute appendicitis (for whom it was assumed that there was no concern of cancer) and in patients with a combination of gallbladder, biliary tract, and pancreas disorders and 6-month and 12-month cancer-free survival following the date of the NFAA diagnosis. The data were analyzed in 2022.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi230038-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>Diagnosis of NFAA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi230038-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary outcome was all-cause mortality among patients with NFAA after adjustment for comorbidities and socioeconomic factors. Secondary outcomes were mortality due to cardiovascular diseases and cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi230038-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 17\u202f726 cases, 10\u202f777 (60.8%) were women, and the median (IQR) age was 65 (57-73) years; among 124\u202f366 controls, 69\u202f514 (55.9%) were women, and the median (IQR) age was 66 (58-73) years. Among cases, overall mortality during the follow-up period (median, 6.2 years [IQR, 3.3-9.6 years]) was higher compared with controls (hazard ratio [HR] 1.43; 95 CI, 1.38-1.48; adjusted HR [aHR], 1.21; 95% CI, 1.16-1.26). The relative association of NFAA with overall mortality was similar in women and men (aHR, 1.22 [95% CI, 1.15-1.28] vs 1.19 [95% CI, 1.11-1.26];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001 in both groups). In contrast, NFAA was associated with a larger increase in mortality among individuals younger than 65 years (aHR, 1.44; 95% CI, 1.31-1.58) than in older individuals (aHR, 1.15; 95% CI, 1.10-1.20;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001  for interaction). Mortality due to cardiovascular diseases was increased (aHR, 1.21; 95% CI, 1.13-1.29), as was mortality due to cancer (aHR, 1.54; 95% CI, 1.42-1.67). The association between NFAA and mortality remained significant and of similar magnitude in all sensitivity analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-ioi230038-10\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>The results of this case-control study suggest that NFAA was associated with an increased overall mortality and mortality of cardiovascular disease and cancer. The increase was more pronounced among younger individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamainternmed.2023.2442","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T11:34:47Z","timestamp":1687779287000},"page":"832","source":"Crossref","is-referenced-by-count":39,"title":["Mortality in Patients With Nonfunctional Adrenal Tumors"],"prefix":"10.1001","volume":"183","author":[{"given":"Jekaterina","family":"Patrova","sequence":"first","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Endocrinology, S\u00f6dersjukhuset, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buster","family":"Mannheimer","sequence":"additional","affiliation":[{"name":"Department of Clinical Science and Education, S\u00f6dersjukhuset, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Endocrinology, S\u00f6dersjukhuset, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatan D.","family":"Lindh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Falhammar","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"8","key":"ioi230038r1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.7326\/M16-0547","article-title":"\u201cNonfunctional\u201d adrenal tumors and the risk for incident diabetes and cardiovascular outcomes: a cohort study.","volume":"165","author":"Lopez","year":"2016","journal-title":"Ann Intern Med"},{"issue":"8","key":"ioi230038r2","doi-asserted-by":"publisher","first-page":"870","DOI":"10.4158\/EP15618.OR","article-title":"Clinical outcomes in adrenal incidentaloma: experience from one center.","volume":"21","author":"Patrova","year":"2015","journal-title":"Endocr Pract"},{"issue":"2","key":"ioi230038r3","doi-asserted-by":"publisher","first-page":"G1","DOI":"10.1530\/EJE-16-0467","article-title":"Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.","volume":"175","author":"Fassnacht","year":"2016","journal-title":"Eur J Endocrinol"},{"issue":"6","key":"ioi230038r4","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1210\/endrev\/bnaa008","article-title":"Adrenal incidentaloma.","volume":"41","author":"Sherlock","year":"2020","journal-title":"Endocr Rev"},{"issue":"5","key":"ioi230038r5","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/S2213-8587(13)70211-0","article-title":"Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing\u2019s syndrome: a 15-year retrospective study.","volume":"2","author":"Di Dalmazi","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"2","key":"ioi230038r6","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1210\/jc.85.2.637","article-title":"A survey on adrenal incidentaloma in Italy.","volume":"85","author":"Mantero","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"ioi230038r7","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1210\/js.2019-00090","article-title":"Cardiovascular outcomes in autonomous cortisol secretion and nonfunctioning adrenal adenoma: a systematic review.","volume":"3","author":"Park","year":"2019","journal-title":"J Endocr Soc"},{"issue":"4","key":"ioi230038r8","doi-asserted-by":"publisher","first-page":"M33","DOI":"10.1530\/EJE-15-0464","article-title":"Cushing\u2019s syndrome: update on signs, symptoms and biochemical screening.","volume":"173","author":"Nieman","year":"2015","journal-title":"Eur J Endocrinol"},{"issue":"12","key":"ioi230038r9","doi-asserted-by":"publisher","first-page":"4462","DOI":"10.1210\/jc.2014-3007","article-title":"Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas.","volume":"99","author":"Debono","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"ioi230038r10","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s12902-020-00599-0","article-title":"The prevalence and characteristics of non-functioning and autonomous cortisol secreting adrenal incidentaloma after patients\u2019 stratification by body mass index and age.","volume":"20","author":"Podbregar","year":"2020","journal-title":"BMC Endocr Disord"},{"issue":"3","key":"ioi230038r11","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1210\/jc.2013-3527","article-title":"Long-term follow-up in adrenal incidentalomas: an Italian multicenter study.","volume":"99","author":"Morelli","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"ioi230038r12","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1530\/EJE-11-1039","article-title":"Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study.","volume":"166","author":"Di Dalmazi","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"ioi230038r13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1210\/js.2019-SAT-368","article-title":"SAT-368 natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: a systematic review and meta-analysis.","volume":"3","author":"Elhassan","year":"2019","journal-title":"J Endocr Soc"},{"issue":"8","key":"ioi230038r14","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.7326\/M20-7946","article-title":"Association between mortality and levels of autonomous cortisol secretion by adrenal incidentalomas: a cohort study.","volume":"174","author":"Kjellbom","year":"2021","journal-title":"Ann Intern Med"},{"issue":"2","key":"ioi230038r15","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s12020-017-1400-8","article-title":"Increased mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: a 13-year retrospective study from one center.","volume":"58","author":"Patrova","year":"2017","journal-title":"Endocrine"},{"issue":"5","key":"ioi230038r16","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1111\/cen.2018.89.issue-5","article-title":"Nonfunctioning adrenal incidentaloma: a novel predictive factor for metabolic syndrome.","volume":"89","author":"Ribeiro Cavalari","year":"2018","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"3","key":"ioi230038r17","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s40618-022-01933-0","article-title":"Congenital adrenal hyperplasia in patients with adrenal tumors: a population-based case-control study.","volume":"46","author":"Sahlander","year":"2023","journal-title":"J Endocrinol Invest"},{"issue":"11","key":"ioi230038r18","doi-asserted-by":"publisher","first-page":"6245","DOI":"10.1007\/s00330-019-06202-y","article-title":"The relationship between adrenal incidentalomas and mortality risk.","volume":"29","author":"Taya","year":"2019","journal-title":"Eur Radiol"},{"issue":"7","key":"ioi230038r19","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/S2213-8587(22)00100-0","article-title":"Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.","volume":"10","author":"Deutschbein","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"1","key":"ioi230038r20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S1043-2760(01)00519-7","article-title":"Hyperplasia versus adenoma in endocrine tissues: are they different?","volume":"13","author":"Derwahl","year":"2002","journal-title":"Trends Endocrinol Metab"},{"issue":"5","key":"ioi230038r21","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1093\/geronb\/gbq049","article-title":"Frontiers in the use of biomarkers of health in research on stress and aging.","volume":"65","author":"Piazza","year":"2010","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"ioi230038r22","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fendo.2019.00054","article-title":"Adrenal aging and its implications on stress responsiveness in humans.","volume":"10","author":"Yiallouris","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"ioi230038r23","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s40618-016-0558-x","article-title":"Follow-up of patients with adrenal incidentaloma, in accordance with the European society of endocrinology guidelines: could we be safe?","volume":"40","author":"Morelli","year":"2017","journal-title":"J Endocrinol Invest"},{"issue":"10","key":"ioi230038r24","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1001\/jamasurg.2022.3544","article-title":"American Association of Endocrine Surgeons guidelines for adrenalectomy: executive summary.","volume":"157","author":"Yip","year":"2022","journal-title":"JAMA Surg"}],"container-title":["JAMA Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/articlepdf\/2806462\/jamainternal_patrova_2023_oi_230038_1690819335.41401.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T11:01:45Z","timestamp":1691406105000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamainternalmedicine\/fullarticle\/2806462"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamainternmed.2023.2442","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742693310.793600687","asserted-by":"object"}]},"ISSN":["2168-6106"],"issn-type":[{"value":"2168-6106","type":"print"}],"subject":[],"published":{"date-parts":[[2023,8,1]]}}}