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Autonomous cortisol secretion – Mortality, morbidity and diagnostics

Kjellbom, Albin LU orcid (2023) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Context
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.

Objectives
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.

Methods
Cohort and cross-sectional studies. Adult patients referred to two Swedish endocrine centres because of an adrenal adenoma, found as an incidentaloma, between 2005... (More)
Context
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.

Objectives
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.

Methods
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
Results
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 (
Conclusions
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.
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author
supervisor
opponent
  • professor Olsson, Tommy, Umeå University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
adrenal incidentaloma (AI), Adrenal adenoma, Cortisol, autonomous cortisol secretion (ACS), Mortality
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2023:61
pages
60 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Zoom: https://lu-se.zoom.us/j/64599862377?pwd=NHBPNy9UNEphWnNsc3VYREErTlhBQT09
defense date
2023-05-17 09:00:00
ISSN
1652-8220
1652-8220
ISBN
978-91-8021-401-8
language
English
LU publication?
yes
id
19d911da-48ea-4575-b678-b86301d3d66c
date added to LUP
2023-04-13 12:10:46
date last changed
2023-10-24 03:07:44
@phdthesis{19d911da-48ea-4575-b678-b86301d3d66c,
  abstract     = {{Context<br/>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.<br/><br/>Objectives<br/>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.<br/><br/>Methods<br/>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 <br/>Results<br/>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 (<br/>Conclusions<br/>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.<br/>}},
  author       = {{Kjellbom, Albin}},
  isbn         = {{978-91-8021-401-8}},
  issn         = {{1652-8220}},
  keywords     = {{adrenal incidentaloma (AI); Adrenal adenoma; Cortisol; autonomous cortisol secretion (ACS); Mortality}},
  language     = {{eng}},
  number       = {{2023:61}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Autonomous cortisol secretion – Mortality, morbidity and diagnostics}},
  url          = {{https://lup.lub.lu.se/search/files/144074249/Albin_Kjellbom_WEBB.pdf}},
  year         = {{2023}},
}