The DOI matches its Crossref record; 48 of the 53 references it cites were found in a registry or an index; none of the 44 sources its claims cite is checked for support yet.
Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas
Open accessAbstract
CONTEXT: Incidental benign adrenocortical adenomas, adrenal incidentalomas are found in 4.5% of abdominal computed tomography scans, with the incidence increasing to 10% in patients older than 70 years of age. These incidentalomas frequently show evidence of excess cortisol secretion but without overt Cushing's syndrome. The mortality rate is increased in Cushing's syndrome. OBJECTIVE: This study sought to investigate whether patients with adrenal incidentalomas have an increased mortality. DESIGN: This was a retrospective, longitudinal cohort study. SETTING: The study was carried out in an Endocrine Investigation Unit in a University Teaching Hospital. PATIENTS: Two hundred seventy-two consecutive patients with an incidental adrenal mass underwent a dedicated diagnostic protocol, which included dexamethasone testing for hypercortisolism between 2005 and 2013. Overall survival was assessed in 206 patients with a benign, adrenocortical adenoma. MAIN OUTCOME MEASURES: Survival analysis was carried out by using Kaplan-Meier curves and the effect of dexamethasone cortisol estimated by Cox-regression analysis. Cause-specific mortality was ascertained from death certificates and compared with local and national data. RESULTS: Eighteen of 206 patients died and the mean time (SD) from diagnosis to death was 3.2 (1.7) years. Seventeen of 18 patients who died had a post dexamethasone cortisol >1.8 μg/dL and there was a significant decrease in survival rate with increasing dexamethasone cortisol levels (P = .001). Compared with the <1.8 μg/dL group, the hazard ratio (95% confidence interval) for the 1.8-5 μg/dL group was 12.0 (1.6-92.6) whereas that of the >5 μg/dL group was 22.0 (2.6-188.3). Fifty percent and 33% of deaths were secondary to circulatory or respiratory/infective causes, respectively. CONCLUSIONS: PATIENTS with adrenal incidentalomas and a post-dexamethasone serum cortisol >1.8 μg/dL have increased mortality, mainly related to cardiovascular disease and infection.
Overview
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Written from the paper’s full text.
TL;DR
In a retrospective cohort of 206 patients with benign adrenocortical incidentalomas, higher post-dexamethasone serum cortisol was associated with increased mortality. Patients with cortisol >1.8 g/dL had markedly worse survival, mainly from circulatory and respiratory/infective causes.
Key findings
- Eighteen of 206 patients died; mean (SD) time from diagnosis to death was 3.2 (1.7) years.
- Seventeen of 18 patients who died had a post-dexamethasone cortisol >1.8 g/dL, and survival decreased with increasing cortisol levels (log-rank trend test, P = .001).
- Compared with the <1.8 g/dL group, hazard ratios (95% CI) were 12.0 (1.6–92.6) for the 1.8–5 g/dL group and 22.0 (2.6–188.3) for the >5 g/dL group.
- Causes of death were 50% circulatory and 33% respiratory/infective; malignancy accounted for 6%, lower than the local/national incidence of 29%.
Methods
- Retrospective, longitudinal cohort study of 272 consecutive patients with incidental adrenal masses referred to an Endocrine Investigation Unit between January 2005 and July 2013; final survival analysis included 206 patients with benign adrenocortical adenoma.
- Patients underwent a dedicated diagnostic protocol including a 1-mg overnight dexamethasone suppression test; cortisol groups were <1.8 g/dL, 1.8–5 g/dL, and >5 g/dL.
- Survival was assessed with Kaplan-Meier curves and log-rank trend tests; hazard ratios were estimated by Cox regression. Cause-specific mortality came from death certificates and was compared with local Sheffield and UK national data; a subanalysis excluded patients with extra-adrenal malignancy (n = 190).
Limitations
- Stated: small number of deaths and retrospective design preclude causative extrapolation; only an initial dexamethasone suppression test was available; dexamethasone levels were not measured; vaccination records were unavailable; hypercortisolism could be secondary to conditions such as alcoholism, depression, or psychotic disease, though no deaths from suicide or alcohol-related issues occurred.
- Stated: multivariable modeling was limited by the small number of events, yielding unstable models and imprecise coefficients.
- Evident from the text: single-center design, no prospective randomized intervention, and inability to determine whether patients died because of or with hypercortisolism.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The neutrophil to lymphocyte ratio was significantly higher in patients with a serum cortisol Ͼ1.8 g/dL post dexamethasone (P ϭ .014).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients with bilateral disease also had a higher post-dexamethasone serum cortisol level, although this relationship was less pronounced (median, 2.25 g/dL [62 nmol/L] bilateral vs 1.8 g/dL [51 nmol/L] unilateral; P ϭ .019).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the hazard ratio (95% confidence interval) for the 1.8 -5g/dL group was 12.0 (1.6 -92.6)”
- Also stated in: § Results · plain
“The hazard ratio (95% confidence interval) for the 1.8 -5-g/dL group was 12.0 (1.6 -92.6) whereas that of the Ͼ5 g/dL group was 22.0 (2.6 -188.3) using the Ͻ1.8-g/dL group as reference.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: A single baseline overnight dexamethasone suppression test adequately classifies long-term cortisol exposure for mortality risk.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Seventeen of 18 patients who died had a post dexamethasone cortisol Ͼ1.8 g/dL”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: A single baseline overnight dexamethasone suppression test adequately classifies long-term cortisol exposure for mortality risk.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there was a significant decrease in survival rate with increasing dexamethasone cortisol levels (P ϭ .001).”
- Also stated in: § Results · boosted
“These show a significant decrease in survival rate that worsens with increasing post-dexamethasone cortisol cutoffs (log-rank trend test, P ϭ .001).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Patients lost to follow-up do not differ systematically in mortality risk from those included in the final analysis.
- Rests on an assumption: A single baseline overnight dexamethasone suppression test adequately classifies long-term cortisol exposure for mortality risk.
- Rests on an assumption: The cohort of patients referred to a single UK endocrine unit is representative of patients with adrenal incidentalomas generally.
- Also stated in: § Results · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eighteen of 206 patients died and the mean time (SD) from diagnosis to death was 3.2 (1.7) years.”
- Also stated in: § Results · plain
“between January 2005 and July 2013 there were 18 deaths.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Patients lost to follow-up do not differ systematically in mortality risk from those included in the final analysis.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the mean time (SD) from diagnosis to death was 3.2 (1.7) years.”
- Also stated in: § Results · plain
“the mean (SD) time from diagnosis to death was 3.2 (1.7) years.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Strength:plain· not yet calibratedn = 18Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas that of the Ͼ5 g/dL group was 22.0 (2.6 -188.3)”
- Also stated in: § Results · plain
“The hazard ratio (95% confidence interval) for the 1.8 -5-g/dL group was 12.0 (1.6 -92.6) whereas that of the Ͼ5 g/dL group was 22.0 (2.6 -188.3) using the Ͻ1.8-g/dL group as reference.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: A single baseline overnight dexamethasone suppression test adequately classifies long-term cortisol exposure for mortality risk.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Patients with adrenal incidentalomas and a post-dexamethasone serum cortisol Ͼ1.8 g/dL have increased mortality, mainly related to cardiovascular disease and infection.”
- Also stated in: § Results · plain
“There was 1/95 (1%) death in the group with post-dexamethasone serum cortisol Ͻ1.8 g/dL.”
- Also stated in: § Results · plain
“Twelve of 92 (13%) and 5/19 (26%) patients in the 1.8 -5 g/dL and Ͼ5 g/dL groups died, respectively.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Patients lost to follow-up do not differ systematically in mortality risk from those included in the final analysis.
- Rests on an assumption: A single baseline overnight dexamethasone suppression test adequately classifies long-term cortisol exposure for mortality risk.
- Rests on an assumption: The cohort of patients referred to a single UK endocrine unit is representative of patients with adrenal incidentalomas generally.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Post-dexamethasone serum cortisol was correlated with size of adenoma (Spearman's ϭ 0.35, P Ͻ .001) and age (Spearman's ϭ 0.32; P Ͻ .001).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 26
- Probably not a substantial claim. 26
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which were higher than the 31% circulatory and the 14% respiratory/infective causes recorded locally in Sheffield, and nationally in the United Kingdom.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Death certificates accurately identify the underlying cause of death.
- Rests on an assumption: Local and national mortality data are comparable to the study cohort.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fifty percent and 33% of deaths were secondary to circulatory or respiratory/infective causes, respectively.”
- Also stated in: § Results · plain
“In our cohort there were 50% circulatory and 33% respiratory/ infective causes of death”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Death certificates accurately identify the underlying cause of death.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Conversely, 6% of our patients died directly resulting from malignancy, a percentage much lower than the local and national incidence of 29% (Figure 3).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Death certificates accurately identify the underlying cause of death.
- Rests on an assumption: Local and national mortality data are comparable to the study cohort.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no relationship between the presence of hypertension (P ϭ .8),dyslipidemia (P ϭ .5),nor diabetes (P ϭ .6)and mortality.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no significant difference in post-dexamethasone serum cortisol between sexes (median 1.88 g/dL [52 nmol/L] women vs 1.92 g/dL [53 nmol/L] men; P ϭ .72).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Post-dexamethasone serum cortisol was correlated with size of adenoma (Spearman's ϭ 0.35, P Ͻ .001) and age (Spearman's ϭ 0.32; P Ͻ .001).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fasting glucose levels were similar in patients who survived or died.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean (95% confidence interval) survival for the post-dexamethasone groups were as follows: cortisol Ͻ1.8, 1.8 -5, and Ͼ5 g/dL was 8.4 (8.2-8.6), 7.3 (6.8 -7.8), and 6.9 (5.6 -8.3) years, respectively.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In our study, however, the mean time to death was 3.2 years.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesThe quote only partly states this claim.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were 15 deaths in total: none with serum cortisol 1.8 g/dL; 10 with serum cortisol 1.8 -5 g/dL (10/85[12%]); and five with a serum cortisol Ͼ5 g/dL (5/16[31%]).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Patients lost to follow-up do not differ systematically in mortality risk from those included in the final analysis.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were observed in the cohort of patients excluding those with extra-adrenal malignancy in whom there were 53, 27, and 7% deaths from circulatory, respiratory/infection, and malignant causes, respectively.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Death certificates accurately identify the underlying cause of death.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data show an increased mortality both from cardiovascular disease and infections in patients with adrenal incidentaloma and low-grade excess cortisol.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The association between post-dexamethasone cortisol category and mortality is not due to unmeasured confounding.
- Rests on an assumption: The recorded causes of death accurately reflect the underlying causes.
None of the sources cited for this claim have been checked yet.
In the paper
“Adrenal incidentalomas secreting excess cortisol are associated with multiple complications including diabetes, hypertension, visceral obesity, low bone mineral density, vertebral fractures, a predisposition to thrombosis (2,15,25,26), and cardiovascular disease (8,15).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [2]
- Not checked yetcites [15]
- Not checked yetcites [25]
- Not checked yetcites [26]
- Not checked yetcites [8]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Cross-sectional data show that increased total cortisol exposure, measured in salivary cortisol samples, a marker of free cortisol, is associated with the development of atherosclerosis in the elderly, independent of the presence of other cardiovascular risk factors (34).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [34]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Locally, all patients diagnosed with adrenal incidentalomas, after radiological investigation, were referred for investigation to the endocrinology unit irrespective of underlying diagnosis and health status.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“An important effect of glucocorticoids is to reduce Th-1 responses needed to counter bacterial infection, and reduce the Th-1:Th-2 cell ratio (41), and lower cellular immunity (42).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [41]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Overt endogenous Cushing's syndrome and use of excess exogenous glucocorticoids are associated with increases in cardiovascular events and mortality from cardiovascular disease or infection (11)(12)(13)(14).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
What the sources say
- Not checked yetcites [11]
- Not checked yetcites [12]
- Not checked yetcites [13]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Changes in cortisol exposure may distort lymphocyte rhythms resulting in impaired immune function.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data, on a consecutive series of patients, extend these observations.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“In most highly selected surgical studies patients with adrenal incidentalomas secreting excess cortisol have experienced improvement in their cardiovascular risk pro-file when compared with patients treated conservatively (30,31), but this finding is not universal (32).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [30]
- Not checked yetcites [31]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“A post-dexamethasone cortisol Ͼ1.8 g/dL is in keeping with a diagnosis of cortisol excess as recommended by Endocrine Society guidelines (20).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Study procedures
What the sources say
- Not checked yetcites [20]
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Nevertheless, a number of studies have shown an increased risk of cardiovascular disease in patients with adrenal incidentalomas (8,9), and a recent study has suggested increased mortality from cardiovascular causes (10).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
What the sources say
- Not checked yetcites [8]
- Not checked yetcites [9]
- Not checked yetcites [10]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The small number of events hampers the extent of modeling, which can be undertaken and the precision of the estimates, but nonetheless the data strongly suggest that hypercortisolemia in the context of an adrenal incidentaloma is detrimental.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“We did, however, carefully ascertain our subjects to define the benign adrenocortical adenoma and assess the significance of the presence of this and excess cortisol as evidenced by dexamethasone testing.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“When excluding patients on drugs that induce CYP3A4 (n ϭ 5) and inhibit CYP3A4 (n ϭ 8) results were similar.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Glucocorticoids also stimulate apoptosis of eosinophils (43) and impair neutrophil apoptosis (44).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [43]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, 21 patients were lost to follow-up.The final survival analysis was carried out on 206 patients (primary analysis).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Setting and participants
Strength:plain· not yet calibratedn = 21Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“which were higher than the 31% circulatory and the 14% respiratory/infective causes recorded locally in Sheffield, and nationally in the United Kingdom.”
- Also stated in: § Results · plain
“a percentage much lower than the local and national incidence of 29% (Figure 3).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
What the sources say
- Not checked yetcites [18]
- Not checked yetcites [19]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Also stated in: § Results · plain
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Dexamethasone levels were not measured, but recent data suggest that measuring dexamethasone levels does not improve the diagnostic performance of the 1-mg overnight dexamethasone-suppression test (45).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A higher neutrophil/lymphocyte ratio in our patients who failed to suppress serum cortisol after dexamethasone might be an indicator of such a relationship.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Under normal circumstances in the young there is a circadian change to the total number of lymphocytes and some lymphocyte subpopulations such as CD3 (total T cells), CD4 (T-helper), and CD20 (total B-cells) with higher levels at night when cortisol levels are lowest, whereas CD8 (T-suppressor and cytotoxic) and CD16 (natural killer) cells are higher at 1200 h (40).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [40]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“This effect may also be explained by the binding of glucocorticoids to glucocorticoid and mineralocorticoid receptors in cardiovascular tissues such as the heart and vascular walls, enhancing contractility of vascular smooth muscle by increasing sensitivity to noradrenaline and decreasing endothelium-dependent vasodilatation (37).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [37]
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Patients with overt Cushing's syndrome have increased mortality due mainly to cardiovascular disease and infection (27).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [27]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Low-grade excess cortisol secretion in adrenal incidentalomas has also been associated with an increased prevalence of insulin resistance, hypertension, and visceral obesity (15)”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Abstract
What the sources say
- Not checked yetcites [15]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“For example, nonsuppression on dexamethasone testing and higher baseline serum cortisol levels has been associated with cardiovascular disease death in patients with mood disorders (33).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [33]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Hypercortisolism and increased sensitivity to glucocorticoids in patients with glucocorticoid receptor polymorphisms have also been associated with severe atherosclerosis and coronary artery disease (36).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
What the sources say
- Not checked yetcites [36]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The model assumption (proportional hazards) was not contradicted by the assessment of residuals, although again the formal tests are limited by the low death rate.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, multivariable modeling was limited by the small number of events (24), which would yield unstable models and imprecise coefficients.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“The average overall life expectancy for the local and national population during this time period was approximately 78 years for men and 82 years for women (18).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Results
What the sources say
- Not checked yetcites [18]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was approved and registered as an institutional case-notes review at Sheffield Teaching Hospitals National Health Service Foundation Trust (Registration No. 5133).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Setting and participants
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The study is reported as recommended by the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines, that recommend parameters to be included in a complete and accurate report of an observational study (17).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Setting and participants
What the sources say
- Not checked yetcites [17]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“It is important to note that our subjects only had an initial dexamethasone suppression test, and this is a limitation of the study.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In the United Kingdom it is recommended for all patients age 65 years and over to receive the flu and pneumococcal vaccines but we did not have any records of this and cannot comment on whether this may have influenced infection-related mortality.”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Hazard ratios could not be calculated because no patients from the Ͻ1.8-g/dL group died (subanalysis).”
§ Cortisol as a Marker for Increased Mortality in Patients with Incidental Adrenocortical Adenomas > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Death certificates accurately identify the underlying cause of death.
“The primary cause of death was ascertained from death certificates obtained from the General Register Office in the United Kingdom so that all-cause and cause-specific mortality could be determined.”
“Death certificates were coded using the 10th revision of the International Classification of Disease (ICD-10).”
The paper relies on this without support.
Patients lost to follow-up do not differ systematically in mortality risk from those included in the final analysis.
“In addition, 21 patients were lost to follow-up.The final survival analysis was carried out on 206 patients (primary analysis).”
The paper relies on this without support.
Local and national mortality data are comparable to the study cohort.
“The cause-specific mortality in the adrenal incidentaloma patients was compared with local incidence figures in 2010 obtained from the Sheffield Director of Public Health Report, 2011 (18).”
The paper relies on this without support.
A single baseline overnight dexamethasone suppression test adequately classifies long-term cortisol exposure for mortality risk.
“Only a baseline overnight dexamethasone suppression test is carried out in our unit (although we do acknowledge that in some cases post-dexamethasone cortisol levels may worsen (10) or normalize (22) on followup).”
The paper relies on this without support.
The cohort of patients referred to a single UK endocrine unit is representative of patients with adrenal incidentalomas generally.
“A retrospective, longitudinal, cohort study was performed on a consecutive series of 272 patients diagnosed with adrenal incidentalomas between January 2005 and July 2013, and referred to the Endocrine Investigation Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals National Health Service Foun-dation Trust, Sheffield, United Kingdom, a University Hospital.”
The paper relies on this without support.
The association between post-dexamethasone cortisol category and mortality is not due to unmeasured confounding.
“When adjusting for age the relationship between postdexamethasone cortisol category and mortality remained identical.”
The paper relies on this without support.
The life expectancy at birth of the general population is a valid comparator for the age at death of patients with adrenal incidentalomas.
“In addition, the age of death for patients with adrenal incidentalomas was lower than the life expectancy at birth of the general population (men/women, 74/72 vs 78/82 y) (18).”
The paper relies on this without support.
The recorded causes of death accurately reflect the underlying causes.
“Graphs show a higher rate of mortality from circulatory and infective/respiratory (resp) causes in the adrenal incidentaloma group of patients between January 2005 and July 2013.”
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 the citing paper
“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 [220]
In the citing paper
“A study with up to 15 years of follow-up in patients with ACS has documented increased cardiovascular morbidity (43% vs 8.8%, P < .005) and mortality (22.6% vs 2.5%, P < .02) in ACS patients compared with nonfunctioning AI.”
From Adrenal incidentaloma (2020) · cites this paper as [220]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Endocrine Society guideline cites the wrong reference
MinorThe text attributes the cortisol cutoff to Endocrine Society guidelines numbered (20), but reference 20 is a patient follow-up study. The reference list identifies the Endocrine Society guideline as reference 18.
“A post-dexamethasone cortisol Ͼ1.8 g/dL is in keeping with a diagnosis of cortisol excess as recommended by Endocrine Society guidelines (20).”
“20. Bernini GP, Moretti A, Oriandini C, Bardini M, Taurino C, Salvetti A. Long-term morphological and hormonal follow-up in a single unit on 115 patients with adrenal incidentalomas. Br J Cancer. 2005;92:1104 -1109.”
Local mortality data cite an unrelated reference
MinorThe cited reference 18 is an Endocrine Society guideline, not the Sheffield Director of Public Health Report named in the text.
“The cause-specific mortality in the adrenal incidentaloma patients was compared with local incidence figures in 2010 obtained from the Sheffield Director of Public Health Report, 2011 (18).”
“18. Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cush- ing's syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:1526 -1540.”
Citations
Cites
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Modeling Survival Data: Extending the Cox Model
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The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline.
Nieman, L. K., Biller, B. M. K., Findling, J. W., Newell-Price, J., Savage, M. O., Stewart, P. M., & Montori, V. M. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0125 · Cited by 2,718
Self-citationThe Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation
Chrousos, G. P. (1995) · New England Journal of Medicine · doi:10.1056/nejm199505183322008 · Cited by 2,579
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Self-citationA Survey on Adrenal Incidentaloma in Italy
Mantero, F. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.2.637 · Cited by 907
Flagged first, then by citations
5 of the 53 references couldn’t be matched to a known paper.
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Items 101–200 of 268
A multidisciplinary approach to the management of adrenal incidentaloma
Voltan, G., Boscaro, M., Armanini, D., Scaroni, C. M., & Ceccato, F. (2021) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2021.1948327 · Cited by 27
“This threshold is supported by studies demonstrating that patients with serum cortisol >50 nmol/L post 1-mg DST have an increased cardiovascular morbidity or mortality [40,41].”
BackgroundFalcetta, P., Orsolini, F., Benelli, E., Agretti, P., Vitti, P., Cosmo, C. D., & Tonacchera, M. (2020) · Endocrine · doi:10.1007/s12020-020-02476-1 · Cited by 25
Goddard, G. M., Ravikumar, A., & Levine, A. C. (2015) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2015.02.009 · Cited by 24
The impact of an adrenal incidentaloma algorithm on the evaluation of adrenal nodules
Eldeiry, L. S., Alfisher, M. M., Callahan, C. F., Hanna, N. N., & Garber, J. R. (2018) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2018.07.001 · Cited by 26
Emerging diagnostic methods and imaging modalities in cushing’s syndrome
Wright, K. E., van Rossum, E. F. C., Zan, E., Werner, N. L., Harris, A. G., Feelders, R. A., & Agrawal, N. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1230447 · Cited by 27
Khadembashiri, M. M., Mohseni, S., Harandi, H., Sani, M. P., Khadembashiri, M. A., Atlasi, R., SeyedAlinaghi, S., Mohajeri‐Tehrani, M. R., & Larijani, B. A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1374711 · Cited by 24
Is Follow-up of Adrenal Incidentalomas Always Mandatory?
Reimondo, G., Muller, A., Ingargiola, E., Puglisi, S., & Terzolo, M. (2020) · Endocrinology and Metabolism · doi:10.3803/enm.2020.35.1.26 · Cited by 23
Frugé, A. D., Cases, M. G., Howell, C. R., Tsuruta, Y., Smith-Johnston, K., Moellering, D. R., & Demark‐Wahnefried, W. (2017) · Cancer Causes & Control · doi:10.1007/s10552-017-0989-5 · Cited by 23
Araujo-Castro, M., García Cano, A., Jiménez Mendiguchía, L., Escobar-Morreale, H. F., & Valderrábano, P. (2021) · Scientific Reports · doi:10.1038/s41598-021-00011-4 · Cited by 24
Management of adrenal incidentalomas: Working through uncertainty
Cambos, S., & Tabarin, A. (2020) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2020.101427 · Cited by 22
Castro, M. A., Guevara, M. I., Gutiérrez, M. C., Ramírez, P. A. P., Gimeno, P. G., Hanzu, F. A., & Lamas, C. (2020) · Endocrinología Diabetes y Nutrición (English ed ) · doi:10.1016/j.endien.2020.08.010 · Cited by 22
Alba, E. L., Japp, E., Fernandez-Ranvier, G. G., Badani, K. K., Wilck, E. J., Ghesani, M. V., Wolf, A., Wolin, E. M., Corbett, V., Steinmetz, D., et al. (2022) · Journal of the Endocrine Society · doi:10.1210/jendso/bvac073 · Cited by 23
“8 μg/dL has been shown to exclude excess cortisol production from an adrenal incidentaloma [3].”
BackgroundFavero, V., Aresta, C., Parazzoli, C., Cairoli, E., Eller-Vainicher, C., Palmieri, S., Salcuni, A. S., Arosio, M., Persani, L., Scillitani, A., et al. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-01836-1 · Cited by 22
Costa, D., Conceição, F. L., Leite, N. C., Ferreira, M. T., Salles, G. F., & Cardoso, C. R. L. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.05.006 · Cited by 22
Attenuation Value in Adrenal Incidentalomas: A Longitudinal Study
Ceccato, F., Tizianel, I., Voltan, G., Maggetto, G., Boschin, I. M., Quaia, E., Crimì, F., & Scaroni, C. M. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.794197 · Cited by 21
“A consistent cohort of patients present a subclinical autonomous cortisol secretion (ACS), without the full-blown clinical picture of overt hypercortisolism (6, 7).”
BackgroundMortality Not Increased in Patients With Nonfunctional Adrenal Adenomas: A Matched Cohort Study
Kjellbom, A., Lindgren, O., Danielsson, M., Olsen, H., & Löndahl, M. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad074 · Cited by 21
Eller-Vainicher, C., Morelli, V., Aresta, C., Salcuni, A. S., Falchetti, A., Carnevale, V., Persani, L., Scillitani, A., & Chiodini, I. (2020) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaa079 · Cited by 20
“In recent years several studies have shown that in patients with incidentally discovered adrenal masses (AIs) but without the classical signs and symptoms of cortisol excess, the presence of a less severe hypercortisolism (previously called autonomous cortisol excess, possible autonomous cortisol excess, or subclinica…”
BackgroundComorbidities in Mild Autonomous Cortisol Secretion – A Clinical Review of Literature
Czapla-Iskrzycka, A., Świątkowska−Stodulska, R., & Sworczak, K. (2022) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1827-4113 · Cited by 20
Olsen, H., Kjellbom, A., Löndahl, M., & Lindgren, O. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01029 · Cited by 21
Remde, H., Kranz, S., Morell, S. M., Altieri, B., Kroiß, M., Detomas, M., Faßnacht, M., & Deutschbein, T. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1123132 · Cited by 19
“Median time from initial diagnosis to surgery was 5 (0-148) months, and median postoperative follow-up was 72 (6-214) months.”
BackgroundDo the diagnostic criteria for subclinical hypercortisolism exist?
Tabarin, A. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.03.013 · Cited by 18
Approach to the Patient with Subclinical Cushing’s Syndrome
Ivović, M., Marina, L., Šojat, A. S., Tančić‐Gajić, M., Arizanović, Z., Kendereški, A., & Vujović, S. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200813134328 · Cited by 18
Recent Advances on Subclinical Hypercortisolism
Zavatta, G., & Dalmazi, G. D. (2018) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2018.01.003 · Cited by 17
Issa, B. G., Hanna, F., Fryer, A. A., Ensah, G., Ebere, I., Marshall, D., & Keevil, B. G. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad242 · Cited by 17
Adrenal incidentaloma: cardiovascular and metabolic effects of mild cortisol excess
Kelsall, A., Iqbal, A., & Newell-Price, J. D. C. (2020) · Gland Surgery · doi:10.21037/gs.2019.11.19 · Cited by 15
“Several retrospective studies have suggested increased prevalence of cardiovascular and metabolic risk factors associated with MCE including hypertension, increased left ventricular mass, impaired glucose tolerance, increased visceral fat and mortality (11-17).”
BackgroundSelf-citationWang, D., Ji, Z., Li, H., & Zhang, Y. (2017) · Cancer Biomarkers · doi:10.3233/cbm-170531 · Cited by 16
“Other studies have shown that the incidence of cardiovascular accidents and related mortality risk in patients with SCS were higher than those in the general population [16].”
Adipokine and cytokine levels in non-functioning adrenal incidentalomas (NFAI)
Babińska, A., Kaszubowski, M. F., & Sworczak, K. (2018) · Endocrine Journal · doi:10.1507/endocrj.ej18-0066 · Cited by 16
“Debono showed that patients with adrenal incidentalomas and cortisol over 50 nmol/L after 1 mg DXM test, have increased mortality, mainly related to cardiovascular disease and infection [23].”
BackgroundInfluentialRowe, N. E., Kumar, R., Schieda, N., Siddiqi, F. S., McGregor, T. B., McAlpine, K., Violette, P. D., Bathini, V., Eng, M. K., & Izard, J. (2023) · Canadian Urological Association Journal · doi:10.5489/cuaj.8248 · Cited by 18
The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome
Kim, H. K., Yoon, J. H., Jeong, Y. A., & Kang, H. (2016) · Endocrinology and Metabolism · doi:10.3803/enm.2016.31.4.592 · Cited by 15
Three-year follow up of adrenal incidentalomas in a New Zealand centre
Goh, Z., Phillips, I., Hunt, P. J., Soule, S., & Cawood, T. J. (2020) · Internal Medicine Journal · doi:10.1111/imj.14332 · Cited by 14
Sagara, R., Inoue, T., Sonoda, N., Yano, C., Motoya, M., Umakoshi, H., Sakamoto, R., & Ogawa, Y. (2021) · Journal of Diabetes Investigation · doi:10.1111/jdi.13653 · Cited by 14
Cardiac Hypertrophy and Related Dysfunctions in Cushing Syndrome Patients—Literature Review
Kanzaki, A., Kadoya, M., Katayama, S., & Koyama, H. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11237035 · Cited by 16
Ren, X., Nan, M., & Zhang, X. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1399311 · Cited by 14
Favero, V., Parazzoli, C., Bernasconi, D. P., & Chiodini, I. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-024-02440-0 · Cited by 16
“However, the risk of cardiometabolic comorbidities in patients with NFAI is still debated, since, so far, most of the available studies have compared patients with NFAI with patients with MACS, with the formers being considered a control group without cortisol excess [4, 6, 36, 37].”
Babińska, A., Kaszubowski, M. F., Kmieć, P., & Sworczak, K. (2018) · Steroids · doi:10.1016/j.steroids.2018.08.011 · Cited by 14
“monstrated in many human malignancies, mainly in the cancers of the breast, reproductive organs, colon and rectum [7].”
Adrenal Incidentaloma: Picking out the High-Risk Patients
Dalmazi, G. D. (2018) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-0713-0598 · Cited by 14
“…by the observation that patients belong ing to three different classes of increasing severity of hypercorti solism (cortisol after DST < 1.8 µg/dL, between 1.8 and 5 µg/dL and > 5 µg/dL, respectively) are at parallel increased risk of allcause and cardiovascularrelated mortality [15].”
InfluentialAutonomous hypercortisolism: definition and clinical implications
Reimondo, G., Puglisi, S., Pia, A. R., & Terzolo, M. (2018) · Minerva Endocrinology · doi:10.23736/s0391-1977.18.02884-5 · Cited by 14
Wada, N., Shibayama, Y., Yoneda, T., Katabami, T., Kurihara, I., Tsuiki, M., Ichijo, T., Ogawa, Y., Kawashima, J., Sone, M., et al. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00131 · Cited by 14
When to Intervene for Subclinical Cushing's Syndrome
Hsieh, L. B., MacKinney, E. C., & Wang, T. S. (2019) · Surgical Clinics of North America · doi:10.1016/j.suc.2019.04.011 · Cited by 14
Markers of Subclinical Cardiovascular Disease in Patients with Adrenal Incidentaloma
Szychlińska, M., Baranowska-Jurkun, A., Matuszewski, W., Wołos-Kłosowicz, K., & Bandurska-Stankiewicz, E. M. (2020) · Medicina · doi:10.3390/medicina56020069 · Cited by 14
Ohno, Y., Sone, M., Inagaki, N., Takeda, Y., Kurihara, I., Tsuiki, M., Ichijo, T., Wada, N., Katabami, T., Ogawa, Y., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-02790 · Cited by 14
The use of prednisolone versus dual-release hydrocortisone in the treatment of hypoadrenalism
Choudhury, S., Tan, T., Lazarus, K., & Meeran, K. M. (2021) · Endocrine Connections · doi:10.1530/ec-20-0473 · Cited by 14
Chen, A., Radhakutty, A., Drake, S. M., Kiu, A., Thompson, C. H., & Burt, M. G. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad665 · Cited by 12
Evaluation of Adrenal Incidentaloma
Hu, J., Kassu, R. A., Titanji, B. N., & Kebebew, E. (2024) · Surgical Clinics of North America · doi:10.1016/j.suc.2024.02.012 · Cited by 11
Cortisol: Analytical and clinical determinants
Vega‐Beyhart, A., Castro, M. A., Hanzu, F. A., & Casals, G. (2022) · Advances in clinical chemistry · doi:10.1016/bs.acc.2022.11.005 · Cited by 12
Cardiovascular status in endogenous cortisol excess: the prospective CV-CORT-EX study
Morbach, C., Detomas, M., Sahiti, F., Hoffmann, K., Kroiß, M., Gelbrich, G., Frantz, S., Hahner, S., Heuschmann, P. U., Faßnacht, M., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae145 · Cited by 10
Rotolo, L., Galante, G., Coscia, K., Bissi, V., Tucci, L., Mezzullo, M., Gambineri, A., Vicennati, V., Zavatta, G., Pagotto, U., et al. (2025) · European Journal of Endocrinology · doi:10.1093/ejendo/lvaf141 · Cited by 11
Work-up of the Incidental Adrenal Mass
Baltzer, P., Clauser, P., Klatte, T., & Walz, J. C. (2015) · European Urology Focus · doi:10.1016/j.euf.2015.12.003 · Cited by 10
“In addition, diagnosis of asymptomatic functional adrenal masses or adrenocortical carcinoma has not lead to an increased survival nor to a better prognosis for the patients diagnosed with such lesions [8,57,58].”
BackgroundPuvaneswaralingam, S., Kjellbom, A., Lindgren, O., Löndahl, M., & Olsen, H. (2020) · Clinical Endocrinology · doi:10.1111/cen.14357 · Cited by 11
Miao, S., Lü, L., Li, L., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.777964 · Cited by 10
“The exclusion criteria were as follows: (1) an enlarged left ventricle and decreased myocardial systolic function resulting from other identified causes, such as long-term poorly controlled hypertension, diabetes, valvular heart disease, congenital or ischemic heart disease; (2) left ventricular wall thickening caused…”
BackgroundMethodBoström, A. E. D., Andersson, P. S. G., Chatzittofis, A., Savard, J., Rask‐Andersen, M., Öberg, K. G., Arver, S., & Jokinen, J. (2022) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2022.105765 · Cited by 10
“Dysregulation of the HPA-axis in humans has also been implicated in sarcopenia (Gupta and John, 2014), longevity (Debono et al., 2014) and prospectively associated with mortality, mainly due to cardiovascular disease and infections (Debono et al., 2014; Jussi Jokinen et al., 2007; Jussi Jokinen and…”
BackgroundInfluentialBonaventura, I., Tomaselli, A., Angelini, F., Ferrari, D., Alcubierre, D. D., Hasenmajer, V., Sbardella, E., Cozzolino, A., Paganini, A. M., Isidori, A. M., et al. (2024) · Journal of Endocrinological Investigation · doi:10.1007/s40618-023-02283-1 · Cited by 11
“Given the observed increase in cardiometabolic morbidity and mortality in patients with MACS [12–15], it stands to reason that the normalization of hypercorti-solism, whether through medical treatment or surgery, should also be considered for these patients.”
BackgroundHigh prevalence of smoking in patients with adrenal incidentalomas: causality or case selection?
Olsen, H., Kjellbom, A., Löndahl, M., & Lindgren, O. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0033 · Cited by 10
Approach to the Patient with an Incidental Adrenal Mass
He, X., Peter, P. R., & Auchus, R. J. (2021) · Medical Clinics of North America · doi:10.1016/j.mcna.2021.06.009 · Cited by 11
Morelli, V., Polledri, E., Mercadante, R., Zhukouskaya, V. V., Palmieri, S., Beck‐Peccoz, P., Spada, A., Fustinoni, S., & Chiodini, I. (2015) · Endocrine · doi:10.1007/s12020-015-0763-y · Cited by 10
Are comorbidities of patients with adrenal incidentaloma tied to sex?
Puglisi, S., Nekić, A. B., Morelli, V., Alessi, Y., Fosci, M., Pani, A., Zibar, K., Palmieri, S., Ferraù, F., Pia, A. R., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1385808 · Cited by 9
DeFronzo, R. A., Auchus, R. J., Bancos, I., Blonde, L., Busch, R. S., Buse, J. B., Findling, J. W., Fonseca, V. A., Frías, J. P., Hamidi, O., et al. (2024) · BMJ Open · doi:10.1136/bmjopen-2023-081121 · Cited by 11
The impact of mild autonomous cortisol secretion and proposed interventions
Iriarte-Durán, M. B., Donato, S., Herrera-Martínez, A. D., Vega, A., Casinello, J. M. J., Marazuela, M., & Castro, M. A. (2025) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2025.2480704 · Cited by 10
“To date, seven studies have investigated mortality in patients with MACS [26,53,74–78].”
Update on Medical Treatment of Cushing’s Syndrome
Dillon, B. R., Agrawal, N., Schwarz, Y., Dancel-Manning, K., Tabarin, A., Lacroix, A., Hofland, L. J., & Feelders, R. A. (2025) · Drugs · doi:10.1007/s40265-025-02223-8 · Cited by 10
Wu, V., Chan, C., Wu, W.-C., Peng, K., Chang, Y.-S., Yeh, F.-Y., Chiang, J., Lee, Y., Liu, K., Wang, S., et al. (2022) · Hypertension Research · doi:10.1038/s41440-022-01086-w · Cited by 9
“These guidelines were based on studies that showed greater mortality and morbidity in ACS patients than in those with nonfunctional adrenal incidentalomas [28, 29].”
MethodThe role of confirmatory tests in the diagnosis of primary aldosteronism
Huang, C., Tu, K., Fan, K., Tsai, C., Wang, W., Wang, S., Wu, C.-Y., Hu, Y.-H., Huang, S.-H., Liu, H.-W., et al. (2023) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2023.04.022 · Cited by 9
Olsen, H., & Mjöman, M. (2015) · Clinical Endocrinology · doi:10.1111/cen.12823 · Cited by 9
Puglisi, S., Leporati, M., Amante, E., Parisi, A., Pia, A. R., Berchialla, P., Terzolo, M., Vincenti, M., & Reimondo, G. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.833514 · Cited by 10
Chen, A., & Burt, M. G. (2022) · Clinical Endocrinology · doi:10.1111/cen.14850 · Cited by 11
“1 mg dexamethasone is associated with a poorer survival rate and an increased risk of cardiovascular events, suggesting risk likely exists on a continuum.(19,22,24,41) In terms of identifying a potential cortisol threshold associated with clinical risk, two recent cohort studies”
BackgroundUpdate on the risks of benign adrenocortical incidentalomas
Dalmazi, G. D. (2017) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000341 · Cited by 9
Olmos, R. I., Mertens, N., Vaidya, A., Uslar, T., Fernandez, P., Guarda, F. J., Zúñiga, Á., Francisco, I. S., Huete, A., & Baudrand, R. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac005 · Cited by 9
Carton, T., Mathieu, E., Wolff, F., Bouziotis, J., Corvilain, B., & Driessens, N. (2021) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.255 · Cited by 8
Can abdominal CT features predict autonomous cortisol secretion in patients with adrenal nodules?
Corwin, M. T., Lan, C., Wilson, M., Loehfelm, T. W., & Campbell, M. J. (2021) · Abdominal Radiology · doi:10.1007/s00261-021-03110-y · Cited by 8
“This is termed mild autonomous cortisol secretion (MACS) and is important to identify as these patients are at increased risk of impaired glucose metabolism, osteoporosis, hypertension, and cardiovascular-related mortality [5, 6].”
BackgroundEspiard, S., Benomar, K., Loyer, C., Vahé, C., & Vantyghem, M. (2017) · Annales d Endocrinologie · doi:10.1016/j.ando.2017.08.002 · Cited by 8
Ceccato, F., Bavaresco, A., Ragazzi, E., Barbot, M., Boscaro, M., Basso, D., Scaroni, C., & Antonelli, G. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgae517 · Cited by 7
Patrova, J., Mannheimer, B., Larsson, M., Lindh, J. D., & Falhammar, H. (2024) · Journal of the Endocrine Society · doi:10.1210/jendso/bvae154 · Cited by 7
“MACS has been associated with increased cardiometabolic risk [9] and increased morbidity and mortality [10-12].”
BackgroundCardiovascular risk factors in mild adrenal autonomous cortisol secretion in a Caucasian population
Adamska, A., Ulychnyi, V., Siewko, K., Popławska‐Kita, A., Szelachowska, M., Adamski, M., Buczyńska, A., & Kretowski, A. J. (2022) · Endocrine Connections · doi:10.1530/ec-22-0074 · Cited by 8
Adrenal incidentalomas, cortisol secretion and cancer: is there a real crosstalk?
Herrera-Martínez, A. D., Román, Á. R., Corrales, E. P., Idrobo, C., Ramírez, P. A. P., Rojas, P. M., Lázaro, C. R., & Castro, M. A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1335202 · Cited by 7
Congenital adrenal hyperplasia is a very rare cause of adrenal incidentalomas in Sweden
Sahlander, F., Bensing, S., & Falhammar, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1017303 · Cited by 7
Rosset, A., Greenman, Y., Osher, E., Stern, N., & Tordjman, K. M. (2021) · Endocrine Practice · doi:10.1016/j.eprac.2021.02.012 · Cited by 7
Plant Natural Compounds in the Treatment of Adrenocortical Tumors
Manso, J., Sharifi‐Rad, J., Zam, W., Fokou, P. V. T., Martorell, M., & Pezzani, R. (2021) · International Journal of Endocrinology · doi:10.1155/2021/5516285 · Cited by 6
“Serum cortisol levels post dexamethasone ≤50 nmol/L without cortisol-related comorbidities exclude autonomous cortisol secretion [18, 21].”
BackgroundAdrenal Incidentaloma: From Silent Diagnosis to Clinical Challenge
Mirică, A., Tilici, D.-M., Păun, D. L., Arnautu, A. M., Nimigean, V., & Paun, S. C. (2025) · Biomedicines · doi:10.3390/biomedicines13092298 · Cited by 5
“In ACS, the pathogenesis of cardiometabolic events appears to be the consequence of hemodynamic changes, vascular inflammatory pathways initiated and maintained by hypercortisolic status, pancreatic β -cell dysfunction, insulin resistance, and visceral obesity [28,32,62].”
InfluentialCurrent approach of primary bilateral adrenal hyperplasia
Delivanis, D. A., Vassiliadi, D. A., & Tsagarakis, S. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000725 · Cited by 5
Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia
Carşote, M., Gheorghe, A.-M., Nistor, C., Trandafir, A.-I., Sima, O.-C., Cucu, A.-P., Ciuche, A., Petrova, E. N., & Ghemigian, A. M. (2023) · Biomedicines · doi:10.3390/biomedicines11113081 · Cited by 6
Unilateral adrenalectomy in primary bilateral macronodular hyperplasia
Cristante, J., & Chabre, O. (2019) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2019.08.001 · Cited by 5
Yamauchi, Y., Kameda, H., Omori, K., Tani, M., Cho, K. Y., Nakamura, A., Miyoshi, H., Tanaka, S., & Atsumi, T. (2021) · BMC Endocrine Disorders · doi:10.1186/s12902-021-00757-y · Cited by 5
“Although no reports on the mortality of SCD are available, adrenal adenomas with mild hypercortisolism cause infection-related mortal outcomes [9].”
BackgroundPlutzky, J., Taub, P. R., Bhatt, D. L., Dhaybi, O. A., Aroda, V. R., BASILE, J. N., Bloch, M. J., Budoff, M. J., Busch, R. S., Buse, J. B., et al. (2026) · JACC Advances · doi:10.1016/j.jacadv.2026.102596 · Cited by 6
“24 32-34 The substantial burden of rHTN establishes an urgent need for greater understanding of its causes, which help inform new treatment strategies.”
Kunz, S. L., Meng, Y., Schneider, H., Brunnenkant, L., Höhne, M., Kuehnle, T., Reincke, M., Theodoropoulou, M., & Bidlingmaier, M. (2024) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2024.106610 · Cited by 4
“…[1,4,5], hyperglycaemia [6,7] and hypertension [1,5,8] which subsequently leads to arteriosclerosis [9,10] and other cardiovascular diseases [1 – 3, 11 , 12 Earlier studies using mammalian cells demonstrated a protective function of 11 β -hydroxysteroid dehydrogenase type 2 (HSD11B2) towards…”
Trandafir, A.-I., Ghemigian, A. M., Ciobica, M.-L., Nistor, C., Gurzun, M., Nistor, T. V. I., Petrova, E. N., & Carşote, M. (2024) · Biomedicines · doi:10.3390/biomedicines12071606 · Cited by 4
“Despite conflicting results, MACS patients have been reported to have an increased risk of mortality, hence the importance of specifically addressing this topic [41,42].”
ResultSato, H., Imamura, Y., Sakamoto, S., Sugiura, M., Arai, T., Yamamoto, S., Takeuchi, N., Sazuka, T., Nakamura, K., Nagano, H., et al. (2020) · International Journal of Urology · doi:10.1111/iju.14445 · Cited by 4
Alcubierre, D. D., Ferrari, D., Tomaselli, A., Moscucci, F., Bonaventura, I., Francia, A. L., Vozza, E., Lospinuso, I., Ettorre, E., Hasenmajer, V., et al. (2026) · European Journal of Endocrinology · doi:10.1093/ejendo/lvag018 · Cited by 5
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Babińska, A., Kmieć, P., & Sworczak, K. (2020) · Archives of Medical Science · doi:10.5114/aoms.2020.93486 · Cited by 3
Analysis of steroid profiles by mass spectrometry: A new tool for exploring adrenal tumors?
Cambos, S., Chanson, P., & Tabarin, A. (2020) · Annales d Endocrinologie · doi:10.1016/j.ando.2020.12.001 · Cited by 3
Pugliese, F., Salcuni, A. S., Battista, C., Carnevale, V., Guglielmi, G., Columbu, C., Velluzzi, F., Giovanelli, L., Eller-Vainicher, C., Scillitani, A., et al. (2021) · Endocrine · doi:10.1007/s12020-021-02616-1 · Cited by 4
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Evaluación diagnóstica y terapéutica del incidentaloma suprarrenal
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Diagnostic Testing for Elevated Cortisol in the Setting of an Adrenal Mass
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“CS was diagnosed when the early morning cortisol level in the 1 mg dexamethasone suppression test was 5.0 μg/dL or higher [16].”
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Metadata
- Authors
- Debono, M., Bradburn, M., Bull, M., Harrison, B., Ross, R. J., & Newell-Price, J.
- Affiliations
- National Health Service (GB)
- University of Sheffield (GB)
- Corresponding author
- Newell-Price, John
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-12
- Volume
- 99
- Issue
- 12
- Pages
- 4462-4470
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4255126
- OpenAlex
- W1968633315
- Semantic Scholar
- 137d1f8a2ad1b183c0a736363bfdd73ae4786040
- Cited by
- 269
- References
- 53
- Citations by year
- 2026: 21 · 2025: 15 · 2024: 18 · 2023: 23 · 2022: 30 · 2021: 35 · 2020: 26 · 2019: 22 · 2018: 24 · 2017: 22 · 2016: 18 · 2015: 15
- FWCI
- 18.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (CL-2013-04-001, BRF-2011-005)
- 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 › Adrenal Hormones and Disorders
- Keywords
- adrenal incidentaloma, adrenal adenoma, cortisol, mortality, dexamethasone suppression test, hypercortisolism, Cushing's syndrome, survival, cardiovascular disease, infection
- MeSH terms
- Adrenal Cortex Neoplasms, Adrenal Gland Neoplasms, Aged, Aged, 80 and over, Dexamethasone, Female, Humans, Hydrocortisone, Longitudinal Studies, Male, Middle Aged, Retrospective Studies, Cohort Studies, Biomarkers, Survival Analysis
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