Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.

Autor:	Deutschbein T; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany; Medicover Oldenburg MVZ, Oldenburg, Germany., Reimondo G; Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy., Di Dalmazi G; Endocrinology and Prevention and Care of Diabetes Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater University of Bologna, Bologna, Italy., Bancos I; Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA., Patrova J; Department of Clinical Science and Education, Södersjukhuset AB, Karolinska Institutet, Stockholm, Sweden., Vassiliadi DA; Department of Endocrinology, Diabetes, and Metabolism, National Expertise Centre for Rare Endocrine Diseases, Evangelismos Hospital, Athens, Greece., Nekić AB; Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia., Debono M; Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK., Lardo P; Endocrinology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy., Ceccato F; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy., Petramala L; Second Hypertension Unit, Department of Translational and Precision Medicine, University Sapienza, Rome, Italy., Prete A; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes, and Metabolism, Birmingham Health Partners, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK., Chiodini I; Istituto Auxologico Italiano, IRCCS, University of Milan, Milan, Italy., Ivović M; Clinic for Endocrinology, Diabetes, and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Pazaitou-Panayiotou K; Department of Endocrinology, Theagenio Cancer Hospital, Thessaloniki, Greece., Alexandraki KI; 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece., Hanzu FA; Endocrinology and Nutrition, Hospital Clinic de Barcelona, Barcelona, Spain., Loli P; Department of Endocrinology, Ospedale Niguarda Cà Granda, Milan, Italy., Yener S; Department of Endocrinology, Dokuz Eylul University School of Medicine, Izmir, Turkey., Langton K; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Dresden, Dresden, Germany., Spyroglou A; Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitäts-Spital Zürich, Zürich, Switzerland; University Hospital Munich, Ludwig-Maximilians-Universität München, Munich, Germany., Kocjan T; Department of Internal Medicine, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Endocrinology, Diabetes, and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia., Zacharieva S; Department of Endocrinology, University Hospital of Endocrinology, Medical University, Sofia, Bulgaria., Valdés N; Hospital Universitario Central de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain; Hospital Universitario de Cabueñes, Gijón, Spain., Ambroziak U; Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland., Suzuki M; Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA., Detomas M; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany., Puglisi S; Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy., Tucci L; Endocrinology and Prevention and Care of Diabetes Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater University of Bologna, Bologna, Italy., Delivanis DA; Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA., Margaritopoulos D; Department of Endocrinology, Diabetes, and Metabolism, National Expertise Centre for Rare Endocrine Diseases, Evangelismos Hospital, Athens, Greece., Dusek T; Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia., Maggio R; Endocrinology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy., Scaroni C; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy., Concistrè A; Second Hypertension Unit, Department of Translational and Precision Medicine, University Sapienza, Rome, Italy., Ronchi CL; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes, and Metabolism, Birmingham Health Partners, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK., Altieri B; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany., Mosconi C; Endocrinology and Prevention and Care of Diabetes Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Diagnostic and Interventional Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Diamantopoulos A; Department of Endocrinology, Diabetes, and Metabolism, National Expertise Centre for Rare Endocrine Diseases, Evangelismos Hospital, Athens, Greece., Iñiguez-Ariza NM; Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA., Vicennati V; Endocrinology and Prevention and Care of Diabetes Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater University of Bologna, Bologna, Italy., Pia A; Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy., Kroiss M; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany; University Hospital Munich, Ludwig-Maximilians-Universität München, Munich, Germany., Kaltsas G; 1st Department of Propaedeutic and Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece., Chrisoulidou A; Department of Endocrinology, Theagenio Cancer Hospital, Thessaloniki, Greece., Marina LV; Clinic for Endocrinology, Diabetes, and Metabolic Diseases, University Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade, Belgrade, Serbia., Morelli V; Istituto Auxologico Italiano, IRCCS, University of Milan, Milan, Italy., Arlt W; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; Centre for Endocrinology, Diabetes, and Metabolism, Birmingham Health Partners, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK; NIHR Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK., Letizia C; Second Hypertension Unit, Department of Translational and Precision Medicine, University Sapienza, Rome, Italy., Boscaro M; Endocrinology Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy., Stigliano A; Endocrinology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy., Kastelan D; Department of Endocrinology, University Hospital Centre Zagreb, Zagreb, Croatia., Tsagarakis S; Department of Endocrinology, Diabetes, and Metabolism, National Expertise Centre for Rare Endocrine Diseases, Evangelismos Hospital, Athens, Greece., Athimulam S; Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA; Division of Endocrinology, Diabetes, Bone and Mineral Disorders, Henry Ford Health System, Detroit, MI, USA., Pagotto U; Endocrinology and Prevention and Care of Diabetes Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, Alma Mater University of Bologna, Bologna, Italy., Maeder U; Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany., Falhammar H; Department of Endocrinology, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Newell-Price J; Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK., Terzolo M; Department of Clinical and Biological Sciences, San Luigi Hospital, University of Turin, Turin, Italy., Fassnacht M; Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany; Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany. Electronic address: fassnacht_m@ukw.de.
Jazyk:	angličtina
Zdroj:	The lancet. Diabetes & endocrinology [Lancet Diabetes Endocrinol] 2022 Jul; Vol. 10 (7), pp. 499-508. Date of Electronic Publication: 2022 May 06.
DOI:	10.1016/S2213-8587(22)00100-0
Abstrakt:	Background: The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing). Methods: We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800-0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50-138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants. Findings: Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53-68]; median follow-up 7·0 years [IQR 4·7-10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19-1·94) and autonomous cortisol secretion (1·77, 1·20-2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93-9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001). Interpretation: Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma. Funding: Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino. Competing Interests: Declaration of interests IB has served as a consultant for Corcept Therapeutics, Sparrow Pharmaceutics, and Spruce Biosciences; was as a member of advisory or data safety monitoring boards for Adrenas Therapeutics, Recordati, and Strongbridge Biopharma (in all cases, institution fees were provided); and reports personal honoraria from Elsevier ClinicalKey. IC reports consulting fees and honoraria from HRA Pharma Rare Diseases and Recordati; was a member of advisory or data safety monitoring boards for HRA Pharma Rare Diseases and Recordati; and has participated in clinical studies from Corcept Therapeutics. ACh reports personal support for attending meetings or travel from Sanofi; personal honoraria from Ipsen; and was a member of advisory or data safety monitoring boards for Ipsen. TDe reports personal consulting fees for being a member of advisory or data safety monitoring boards for HRA Pharma Rare Diseases and Recordati; personal honoraria from Novartis; and has participated in clinical studies from Corcept Therapeutics and HRA Pharma Rare Diseases (for these, institution fees were provided). MF has participated in clinical studies from Corcept Therapeutics and HRA Pharma Rare Diseases (for these, institution fees were provided). LM was a member of the expert panel “Focus Area Adrenal and Cardiovascular Endocrinology” from the European Society of Endocrinology, and led the working group 5 of the project “CA20122—Harmonizing clinical care and research on adrenal tumours in European countries” from the European Cooperation in Science in Technology. JN-P reports grants from Diurnal Group; and has served as a consultant for and received honoraria from HRA Pharma Rare Diseases, Crinetics Pharmaceuticals, and Recordati (in all cases, institution fees were provided). CS reports consulting fees and honoraria from HRA Pharma Rare Diseases and Recordati; was a member of advisory or data safety monitoring boards for HRA Pharma Rare Diseases and Recordati; and has served as coordinator of the Pituitary Club of the Italian Society of Endocrinology. MT reports personal consulting fees (for being a member of advisory or data safety monitoring boards for Corcept Therapeutics and HRA Pharma Rare Diseases); and has participated in clinical studies from HRA Pharma Rare Diseases (for which institution fees were provided). ST reports personal support for attending meetings or travel from Ipsen, Pfizer, and Recordati; personal honoraria from Recordati; and has participated in clinical studies from Crinetics Pharmaceuticals, Novartis, and Strongbridge Biopharma. All other authors declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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