Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas

Abstract

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.

Figures

Figure 1.

Recruitment Strategy Flow chart. Patients attending for incidentaloma protocol at an Endocrine Investigation Unit between January 2005 and July 2013.

Figure 2.

A, Kaplan-Meier survival curve in patients categorized according to post dexamethasone cortisol levels. This shows worsening survival with increasing post dexamethasone serum cortisol levels (log rank P = .001) categorized using standard cut-offs from literature (<1.8 μg/dL, 1.8–5 μg/dL, >5 μg/dL) (Primary analysis). B, Kaplan-Meier survival curve in patients categorized according to post-dexamethasone cortisol levels. This shows worsening survival with increasing post dexamethasone serum cortisol levels (log-rank P < .001) after excluding patients with benign adrenocortical adenomas and extra-adrenal malignancy. Hazard ratios could not be calculated because no patients from the <1.8-μg/dL group died (subanalysis).

Figure 3.

Causes of mortality. Mortality rate in adrenal incidentalomas compared with local incidence mortality (Sheffield) and national incidence mortality (United Kingdom). 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.