Autonomous cortisol secretion – Mortality, morbidity and diagnostics

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Up to half of patients with adrenal adenomas found as incidentalomas show biochemical signs of subtle cortisol hypersecretion without having clinical signs or symptoms of Cushing’s syndrome. A condition called autonomous cortisol secretion (ACS). Previous studies have indicated that ACS might be associated with increased mortality.

Explore if ACS is an independent risk factor for increased mortality. Evaluate low ACTH as a diagnostic marker of ACS. Investigate the prevalence of smoking in patients with adrenal adenomas.

Cohort and cross-sectional studies. Adult patients referred to two Swedish endocrine centres because of an adrenal adenoma, found as an incidentaloma, between 2005 and 2015 were enrolled. Mortality data were obtained from the Cause of Death Register. Patients were grouped according to predefined levels of cortisol after a 1-mg dexamethasone suppression test (cortisolDST); non-functional adrenal adenoma (NFAA), defined as cortisolDST
1048 patients were followed for 6.4 years. Compared with NFAA mortality was not increased in cortisolDST 50-82 nmol/L, hazard ratio (HR) 1.17 (95% CI, 0.79-1.73)), while cortisolDST 83-137 and ≥138 nmol/L were associated with a significant increase in mortality, HR 2.33 (1.53-3.53) and 2.87 (1.74-4.74). Mortality did not differ significantly between 632 patients with NFAA and matched controls (3:1) when followed for 6.6 years, HR 1.13 (0.87-1.46). Studying 198 patients with unilateral adrenal adenomas and 100 healthy controls, low ACTH (
ACS is an independent risk factor for increased mortality, while NFAAs do not pose a relevant risk. The risk associated with ACS seems to become clinically relevant when the cortisolDST level is ≥83 nmol/L. Low ACTH is of limited value in diagnosing ACS, in part due to its high prevalence in patients with NFAA. Additionally, there appears to be a link between smoking, adrenal adenomas, and ACS.
Original languageEnglish
Awarding Institution
  • Department of Clinical Sciences, Lund
  • Löndahl, Magnus, Supervisor
  • Lindgren, Ola, Assistant supervisor
  • Olsen, Henrik, Assistant supervisor
Award date2023 May 17
Place of PublicationLund
ISBN (Print)978-91-8021-401-8
Publication statusPublished - 2023

Bibliographical note

Defence details
Date: 2023-05-17
Time: 09:00
Place: Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Zoom: 
External reviewer(s)
Name: Olsson, Tommy
Title: professor
Affiliation: Umeå University

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Free keywords

  • adrenal incidentaloma (AI)
  • Adrenal adenoma
  • Cortisol
  • autonomous cortisol secretion (ACS)
  • Mortality


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