CoChat
Sign Up
Cited by 415Adrenal and Paraganglionic TumorsPituitary Gland Disorders and TreatmentsHormonal Regulation and Hypertension

Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing’s syndrome: a 15-year retrospective study

Di Dalmazi, Guido, Vicennati, Valentina, Garelli, Silvia, Casadio, Elena, Rinaldi, Eleonora, Giampalma, Emanuela, Mosconi, Cristina, Golfieri, Rita +3 more·2014·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(13)70211-0
Open this paper in CoChat — free account

Abstract

Background Incidental discovery of adrenal masses has increased over the past few years. Mild alterations in cortisol secretion without clinical signs of overt hypercortisolism (subclinical Cushing's syndrome) are a common finding in patients with these tumours. Although metabolic alterations and increased cardiovascular risk have been noted in patients with subclinical Cushing's syndrome, incidence of cardiovascular events and mortality in the long term have not been assessed. We aimed to ascertain the frequency of new cardiovascular events and mortality in patients with non-secreting adrenal incidentalomas, tumours of intermediate phenotype, or those causing subclinical Cushing's syndrome.Methods From January, 1995, to September, 2010, consecutive outpatients with adrenal incidentalomas who were referred to the endocrinology unit of S Orsola-Malpighi Hospital, Bologna, Italy, were enrolled into our study. Individuals were assessed every 18-30 months for the first 5 years (mean follow-up 7·5 [SD 3·2] years, range 26 months to 15 years). Cortisol concentrations after the 1 mg dexamethasone suppression test (DST) were used to define non-secreting (+50 nmol/L) and intermediate phenotype (50-138 nmol/L) adrenal incidentalomas and subclinical Cushing's syndrome (+138 nmol/L). At the end of follow-up, patients were reclassified as having either unchanged or worsened secreting patterns from baseline.Findings 198 outpatients were assessed; at the end of follow-up, 114 patients had stable non-secreting adrenal incidentalomas, 61 had either a stable intermediate phenotype or subclinical Cushing's syndrome, and 23 had a pattern of secretion that had worsened. By comparison with patients with stable non-secreting adrenal incidentalomas, the incidence of cardiovascular events was higher in individuals with a stable intermediate phenotype or subclinical Cushing's syndrome (6·7% vs 16·7%; p=0·04) and in those with worsened secreting patterns (6·7% vs 28·4%; p=0·02). Cardiovascular events were associated independently with a change (from baseline to the end of follow-up) in cortisol concentrations post DST (hazard ratio 1·13, 95% CI 1·05-1·21; p=0·001). Survival rates for all-cause mortality were lower in patients with either stable intermediate phenotype adrenal incidentalomas or subclinical Cushing's syndrome compared with those with stable non-secreting masses (57·0% vs 91·2%; p=0·005). Factors associated with mortality were age (hazard ratio 1·06, 95% CI 1·01-1·12; p=0·03) and mean concentrations of cortisol post DST (1·10, 1·01-1·19; p=0·04). Compared with patients with stable non-secreting adrenal incidentalomas, unadjusted survival for cardiovascular-specific mortality was lower in patients with either a stable intermediate phenotype or subclinical Cushing's syndrome (97·5% vs 78·4%; p=0·02) and in those with worsened secreting patterns (97·5% vs 60·0%; p=0·01). Cancer mortality did not differ between groups.Interpretation Even when clinical signs of overt hypercortisolism are not present, patients with adrenal incidentalomas and mild hypercortisolism have an increased risk of cardiovascular events and mortality.Funding None.

Integrity signals

Registry

Crossref · 10.1016/s2213-8587(13)70211-0

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In patients with adrenal incidentalomas, post-DST cortisol levels are related to cardiovascular events and all-cause mortality.

    “It was shown that in patients with adrenal incidentalomas post-DST cortisol levels are related to cardiovascular events and all-cause mortality (88).”

    From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [88]

  • Cortisol levels between 1.9 and 5.0 μg/dL may indicate possible autonomous cortisol secretion, and cortisol levels above 5.0 μg/dL are suggested to confirm autonomous cortisol secretion.

    “Levels between 1.9 and 5.0 μg/dL (50-140 nmol/L) may indicate “possible autonomous cortisol secretion,” and cortisol levels above 5.0 μg/dL (140 nmol/L) are suggested to confirm ACS (79,220).”

    From Adrenal incidentaloma (2020) · cites this paper as [79]

  • A recent systematic review showed that patients with autonomous cortisol secretion had a higher prevalence of cardiovascular events (16.7-26.8%) compared with patients with nonfunctional adrenal incidentaloma (6.7-10.4%).

    “A recent systematic review showed that ACS patients had a higher prevalence of cardiovascular events (16.7-26.8%) compared with patients with nonfunctional AI (6.7-10.4%) (79,244,245,247).”

    From Adrenal incidentaloma (2020) · cites this paper as [79]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Di Dalmazi, G., Vicennati, V., Garelli, S., Casadio, E., Rinaldi, E., Giampalma, E., Mosconi, C., Golfieri, R., Paccapelo, A., Pagotto, U., & Pasquali, R.
Affiliations
IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
ORCID
Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2014-05
Volume
2
Issue
5
Pages
396-405
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(13)70211-0
OpenAlex
W2095927474
Cited by
415
References
40
Citations by year
2026: 25 · 2025: 31 · 2024: 35 · 2023: 40 · 2022: 40 · 2021: 44 · 2020: 39 · 2019: 27 · 2018: 34 · 2017: 35 · 2016: 28 · 2015: 19 · 2014: 17
FWCI
32.67
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
adrenal incidentaloma, subclinical Cushing's syndrome, endophenotypes, cardiovascular events, mortality, cortisol secretion, dexamethasone suppression test, long-term follow-up, adrenal tumors, cardiovascular risk
MeSH terms
Adrenal Gland Neoplasms, Aged, Cardiovascular Diseases, Cushing Syndrome, Female, Follow-Up Studies, Humans, Male, Middle Aged, Phenotype, Retrospective Studies

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review