Effect of surgical versus conservative management on cardiovascular outcomes in patients with bilateral adrenal tumours and cortisol excess: an international, retrospective cohort study
Nowak, Elisabeth Viëtor, Charlotte L Feelders, Richard A Hofland, Johannes Castro, Marta Araujo Ojeda, César Minguéz Pascual-Corrales, Eider Salama, Bahaa Bancos, Irina Sandooja, Rashi
Nowak, Elisabeth
Viëtor, Charlotte L
Feelders, Richard A
Hofland, Johannes
Castro, Marta Araujo
Ojeda, César Minguéz
Pascual-Corrales, Eider
Salama, Bahaa
Bancos, Irina
Sandooja, Rashi
Affiliation
Ludwig Maximilian University Hospital; Ludwig Maximilian University of Munich; Erasmus Medical Center; Erasmus University Medical Center; New York University Langone Medical Center; Hospital Universitario Ramón y Cajal; Instituto de Investigación Ramón y Cajal; Mayo Clinic; University of Nebraska Medical Center; University Hospital of Würzburg; Medical University of Warsaw; University of Turin; Hospital Universitario Central de Asturias Oviedo; Instituto de Investigación Sanitaria del Principado de Asturias; Instituto de Salud Carlos III; University of Oviedo; University Hospital of Padova; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; University of Milan; Grande Ospedale Metropolitano Niguarda; University of Birmingham; University Hospitals Birmingham NHS Foundation Trust; National Institute for Health and Care Research Birmingham Biomedical Research Centre; Prince of Songkla University; Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Auxiologico Italiano; Jagiellonian University Medical College; S Luigi Gonzaga Hospital; University of Turin; Aretaieio Hospital; National and Kapodistrian University of Athens; Karolinska University Hospital; Karolinska Institutet; Medical University of Gdańsk; University Clinical Center Gdańsk; Theagenio Cancer Hospital; University Hospital of Bordeaux; Clinica San Carlo; European Reference Network Center on Rare Endocrine Conditions; Laikon General Hospital; Centro Hospitalar Universitário de São João; University of Porto; Hospital Clínic of Barcelona; University Barcelona; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; Technische Universität; University Hospital and Medical Faculty Carl Gustav Carus; Henry Ford Health; Endocrinology in Charlottenburg; Athens General Hospital "G Gennimatas"; Changi General Hospital; Duke University-National University of Singapore Medical School; Medicover Oldenburg MVZ
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Publication date
2026-01-21
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Abstract
Background: Treatment for patients with bilateral adrenal tumours and cortisol excess is not standardised and poses a therapeutic dilemma. Untreated cortisol excess is associated with cardiometabolic morbidity and mortality, but bilateral adrenalectomy causes adrenal insufficiency and possibly life-threatening adrenal crises. Data on cardiovascular outcomes by treatment modality are scarce. In this study we aimed to evaluate mid-term and long-term clinical and biochemical outcomes in patients with bilateral adrenal tumours and cortisol excess by treatment strategy and diagnosis.
Methods: This retrospective, international cohort study (in 30 centres across 10 countries in Europe plus Singapore and the USA) included patients with bilateral adrenal tumours of 10 mm or larger, post-dexamethasone serum cortisol concentration of 50 nmol/L or higher, and at least 36 months of follow-up, with data collection beween Feb 2, 2024, and Jan 31, 2025. Patients were excluded if they had adrenocorticotropin hormone (ACTH)-dependent cortisol excess, ACTH-dependent nodular adrenal hyperplasia, partial glucocorticoid resistance syndrome, a diagnosis inconsistent with benign adrenocortical lesions, or received systemic oral or intravenous glucocorticoids other than replacement therapy following adrenalectomy. Primary endpoints were all-cause mortality and clinical and biochemical remission rates. Secondary endpoints were the incidence of cardiovascular events, prevalence of vascular and metabolic comorbidities, and incidence of adrenal crises.
Findings: Of 629 patients who were diagnosed between Jan 1, 2000, and Jan 31, 2022, 105 (17%) had Cushing's syndrome and 524 (83%) had mild autonomous cortisol secretion (MACS), median age was 62 years (IQR 54·0-68·0), and 426 (68%) were female. 85 (81%) of 105 patients with Cushing's syndrome underwent surgery, and 384 (73%) of 524 patients with MACS received non-specific symptomatic treatment (ie, never underwent adrenalectomy or received steroidogenesis inhibitors). Over a median follow-up of 6·8 years, biochemical remission was achieved in 46 (45%) of 102 patients with Cushing's syndrome and in 67 (13%) of 517 patients with MACS. In both groups, 7% of patients died (Cushing's syndrome: seven of 105; MACS: 38 of 524) and 12% (13 of 105) of patients with Cushing's syndrome and 16% (82 of 524) of those with MACS had at least one cardiovascular event, without substantial differences across treatments. Smoking emerged as key modifiable mortality and cardiovascular risk factor in all patients, and in patients with MACS who only received non-specific symptomatic therapy, post-dexamethasone cortisol was also associated with increased mortality. Bilateral adrenalectomy led to full biochemical remission, few non-fatal adrenal crises, and improved arterial hypertension. Unilateral adrenalectomy and steroidogenesis inhibitors yielded heterogeneous biochemical outcomes and no substantial comorbidity improvement. Non-specific symptomatic treatment in MACS was associated with worsening of all investigated comorbidities.
Interpretation: Although mortality and cardiovascular event rates were similar across treatments, surgery led to better biochemical control and more favourable comorbidity outcomes.
Citation
Nowak E, Viëtor CL, Feelders RA, Hofland J, Castro MA, Ojeda CM, Pascual-Corrales E, Salama B, Bancos I, Sandooja R, Fassnacht M, Altieri B, Detomas M, Bobrowicz M, Ambroziak U, Gladka A, Giordano R, Bioletto F, Parasiliti-Caprino M, Torre EM, Rivas-Otero D, González-Vidal T, Ceccato F, Tizianel I, Torchio M, Palmieri S, Mangone A, Mantovani G, Chiodini I, Favero V, Prete A, Suntornlohanakul O, Morelli V, Chiodaroli M, Trofimiuk-Müldner M, Hubalewska-Dydejczyk A, Puglisi S, Reimondo G, Alexandraki KI, Spyroglou A, Falhammar H, Kłosowski P, Chrisoulidou A, Tabarin A, Loli P, Angelousi A, Pignatelli D, Hanzu F, Fuld S, Pamporaki C, Athimulam S, Quinkler M, Markou A, Puar T, Deutschbein T, Hoffmann VS, Reincke M. Effect of surgical versus conservative management on cardiovascular outcomes in patients with bilateral adrenal tumours and cortisol excess: an international, retrospective cohort study. Lancet Diabetes Endocrinol. 2026 Jan 21:S2213-8587(25)00302-X. doi: 10.1016/S2213-8587(25)00302-X. Epub ahead of print.
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Article