title: Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study.
abstract: BACKGROUND
  Subclinical Cushing's syndrome (SCS) is defined as alterations in hypothalamic-pituitary-adrenal axis without classic signs/symptoms of glucocorticoid excess. Whether SCS leads to metabolic and cardiovascular diseases is still controversial.
  
  
  OBJECTIVE
  To evaluate the prevalence of hypertension, type 2 diabetes (T2D), coronary heart disease (CHD), ischemic stroke, osteoporosis, and fractures, and their relationship to increasing patterns of subclinical hypercortisolism, in patients with nonsecreting adrenal adenomas (NSA) and SCS.
  
  
  METHODS
  Using the 1 mg dexamethasone suppression test (DST), 348 patients were classified as follows: 203 were defined as NSA and 19 SCS, using the most stringent cutoff values (<50 and >138 nmol/l respectively). Patients with cortisol post-DST (50-138 nmol/l) were considered as intermediate phenotypes and classified as minor (n=71) and major (n=55) using plasma ACTH and/or urinary free cortisol as additional diagnostic tools.
  
  
  RESULTS
  SCS patients showed higher prevalence of T2D, CHD, osteoporosis, and fractures with respect to NSA. Intermediate phenotypes also showed higher prevalence of CHD and T2D with respect to NSA. The prevalence of all clinical outcomes was not different between intermediate phenotype patients, which were therefore considered as a single group (IP) for multivariate logistic regression analysis: both IP and SCS-secreting patterns showed a significant association with CHD (odds ratio (OR), 4.09; 95% confidence interval (CI), 1.47-11.38 and OR, 6.10; 95% CI, 1.41-26.49 respectively), independently of other potential risk factors. SCS was also independently associated with osteoporosis (OR, 5.94; 95% CI, 1.79-19.68).
  
  
  CONCLUSIONS
  Patterns of increasing subclinical hypercortisolism in adrenal adenomas are associated with increased prevalence of adverse metabolic and cardiovascular outcomes, independently of other potential risk factors.
authors.affiliation: Endocrinology Unit, Department of Clinical Medicine, S. Orsola-Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Via Massarenti 9, Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Di Dalmazi
authors.forename: Valentina
authors.initials: V
authors.lastname: Vicennati
authors.forename: Eleonora
authors.initials: E
authors.lastname: Rinaldi
authors.forename: Antonio Maria
authors.initials: AM
authors.lastname: Morselli-Labate
authors.forename: Emanuela
authors.initials: E
authors.lastname: Giampalma
authors.forename: Cristina
authors.initials: C
authors.lastname: Mosconi
authors.forename: Uberto
authors.initials: U
authors.lastname: Pagotto
authors.forename: Renato
authors.initials: R
authors.lastname: Pasquali
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003480:Cushing Syndrome / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D003937:Diagnosis, Differential; D003940:Diagnostic Techniques, Endocrine; D018450:Disease Progression; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D006854:Hydrocortisone