Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study. Issue 7 (July 2022)

• Record Type: Journal Article
• Authors: Deutschbein, Timo; Reimondo, Giuseppe; Di Dalmazi, Guido; Bancos, Irina; Patrova, Jekaterina; Vassiliadi, Dimitra Argyro; Nekić, Anja Barač; Debono, Miguel; Lardo, Pina; Ceccato, Filippo; Petramala, Luigi; Prete, Alessandro; Chiodini, Iacopo; Ivović, Miomira; Pazaitou-Panayiotou, Kalliopi; Alexandraki, Krystallenia I; Hanzu, Felicia Alexandra; Loli, Paola; Yener, Serkan; Langton, Katharina; Spyroglou, Ariadni; Kocjan, Tomaz; Zacharieva, Sabina; Valdés, Nuria; Ambroziak, Urszula; Suzuki, Mari; Detomas, Mario; Puglisi, Soraya; Tucci, Lorenzo; Delivanis, Danae Anastasia; Margaritopoulos, Dimitris; Dusek, Tina; Maggio, Roberta; Scaroni, Carla; Concistrè, Antonio; Ronchi, Cristina Lucia; Altieri, Barbara; Mosconi, Cristina; Diamantopoulos, Aristidis; Iñiguez-Ariza, Nicole Marie; Vicennati, Valentina; Pia, Anna; Kroiss, Matthias; Kaltsas, Gregory; Chrisoulidou, Alexandra; Marina, Ljiljana V; Morelli, Valentina; Arlt, Wiebke; Letizia, Claudio; Boscaro, Marco; Stigliano, Antonio; Kastelan, Darko; Tsagarakis, Stylianos; Athimulam, Shobana; Pagotto, Uberto; Maeder, Uwe; Falhammar, Henrik; Newell-Price, John; Terzolo, Massimo; Fassnacht, Martin;
• Is Part Of: Lancet. Volume 10:Issue 7(2022)
• Page Start: 499
• Page End: 508
• Publication Date: 2022-07
• Subjects: Diabetes -- Periodicals; Endocrinology -- Periodicals; Endocrine glands -- Diseases -- Periodicals; 616.4
• DOI: 10.1016/S2213-8587(22)00100-0
• Languages: English
• ISSNs: 2213-8587

Abstract

Summary: 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.