• Valentina Morelli, Giuseppe Reimondo, Roberta Giordano, Silvia Della Casa, Caterina Policola, Serena Palmieri, Antonio S Salcuni, Alessia Dolci, Marco Mendola, Maura Arosio, Bruno Ambrosi, Alfredo Scillitani, Ezio Ghigo, Paolo Beck-Peccoz, Massimo Terzolo, and Iacopo Chiodini.
• Department of Clinical Sciences and Community Health (V.M., S.P., A.D., M.A., P.B.-P., I.C.), University of Milan, 20122 Milan, Italy; Unit of Endocrinology and Diabetology (V.M., S.P., P.B.-P., I.C.), Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy; Division of Internal Medicine I (G.R., M.T.), Ospedale San Luigi, 10043 Orbassano, Italy; Department of Biological and Clinical Sciences (G.R., R.G., M.T.), University of Turin, 10124 Turin, Italy; Catholic University (S.D.C., C.P.), Unit of Endocrinology and Metabolism, 00168 Rome, Italy; Unit of Endocrinology (A.S.S., A.S.), Ospedale "Casa Sollievo della Sofferenza," IRCCS, 71013 San Giovanni Rotondo, Foggia, Italy; Unit of Endocrine Diseases and Diabetology (A.D., M.A.), Ospedale San Giuseppe, Gruppo Multimedica, 20123 Milan, Italy; Department of Biomedical Sciences for Health (M.M., B.A.), University of Milan, Unit of Endocrinology and Diabetology, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Milan, Italy; and Division of Endocrinology, Diabetology, and Metabolism (E.G.), Department of Medical Sciences, University of Turin, 10124 Turin, Italy.
• J. Clin. Endocrinol. Metab. 2014 Mar 1; 99 (3): 827-34.

ContextThe long-term consequences of subclinical hypercortisolism (SH) in patients with adrenal incidentalomas (AIs) are unknown.Setting And PatientsIn this retrospective multicentric study, 206 AI patients with a ≥5-year follow-up (median, 72.3 mo; range, 60-186 mo) were enrolled.Intervention And Main Outcome MeasuresAdrenocortical function, adenoma size, metabolic changes, and incident cardiovascular events (CVEs) were assessed. We diagnosed SH in 11.6% of patients in the presence of cortisol after a 1 mg-dexamethasone suppression test >5 μg/dL (138 nmol/L) or at least two of the following: low ACTH, increased urinary free cortisol, and 1 mg-dexamethasone suppression test >3 μg/dL (83 nmol/L).ResultsAt baseline, age and the prevalence of CVEs and type 2 diabetes mellitus were higher in patients with SH than in patients without SH (62.2 ± 11 y vs 58.5 ± 10 y; 20.5 vs 6%; and 33.3 vs 16.8%, respectively; P < .05). SH and type 2 diabetes mellitus were associated with prevalent CVEs (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0; and OR, 2.0; 95% CI, 1.2-3.3, respectively), regardless of age. At the end of the follow-up, SH was diagnosed in 15 patients who were without SH at baseline. An adenoma size >2.4 cm was associated with the risk of developing SH (sensitivity, 73.3%; specificity, 60.5%; P = .014). Weight, glycemic, lipidic, and blood pressure control worsened in 26, 25, 13, and 34% of patients, respectively. A new CVE occurred in 22 patients. SH was associated with the worsening of at least two metabolic parameters (OR, 3.32; 95% CI, 1.6-6.9) and with incident CVEs (OR, 2.7; 95% CI, 1.0-7.1), regardless of age and follow-up.ConclusionSH is associated with the risk of incident CVEs. Besides the clinical follow-up, in patients with an AI >2.4 cm, a long-term biochemical follow-up is also required because of the risk of SH development.

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