Mortality in Patients With Nonfunctional Adrenal Tumors

Abstract

ImportanceIt is unclear if nonfunctional adrenal adenomas (NFAAs) are associated with increased mortality.ObjectiveTo analyze mortality and causes of death in patients with NFAA.Design, Setting, and ParticipantsA national retrospective register-based case-control study was conducted and included 17 726 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 124 366 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.ExposuresDiagnosis of NFAA.Main Outcomes and MeasuresThe 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.ResultsAmong 17 726 cases, 10 777 (60.8%) were women, and the median (IQR) age was 65 (57-73) years; among 124 366 controls, 69 514 (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]; P < .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; P < .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.Conclusions and RelevanceThe 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.

Nonfunctional Adrenal Adenomas and Increased Risk of Mortality

“…To the Editor We read with interest the retrospective case-control study by Patrova et al, who demonstrated that nonfunctional adrenal adenoma (NFAA) was associated with an increased overall mortality and mortality owing to cardiovascular disease and cancer. With the lack of data on adrenal hormone measurements, the authors speculated that the development of even slightly elevated cortisol may result in increased cardiovascular disease.…”

“…Screening and confirmation of hyperaldosteronism has traditionally been dichotomous and complex with great variability in reported diagnostic criteria and prevalence . The conclusions of the article would have been further enhanced by reporting the number of patients excluded because they had received renin and aldosterone measurements to support the diagnosis of primary aldosteronism syndrome.…”

“…Similarly, subclinical aldosteronism has been associated with increased cardiovascular disease . We support the authors’ suggestion of the need to determine which patients with NFAA require greater follow-up, including adrenal hormone measurements—and suggest that most likely they would be those with evidence of subclinical or autonomous hormone secretion.…”

Nonfunctional Adrenal Adenomas and Increased Risk of Mortality

“…To the Editor We read with great interest the article by Patrova et al on the risk of mortality in patients with nonfunctional adrenal tumors. This study addresses a topic of pivotal importance in adrenal disease that has been the subject of intense research interest in recent years.…”

“…However, in the article by Patrova et al, the use of NFAA can be misleading. In this population-based retrospective cohort study, the exclusion criteria for hormonal activity were based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision ( ICD-10 ) classification codes, according to which patients with Cushing syndrome ( ICD-10 code, E24.0), congenital adrenal hyperplasia (E25.0), primary aldosteronism (E26.0), and pheochromocytoma (E27.5) were excluded from the analyses.…”