1. Adrenal incidentalomas patients with severely elevated cortisol levels following a dexamethasone suppression test were shown to have a three-time increase in the risk of mortality compared to patients without autonomous cortisol secretion.
2. The relationship between cortisol level and mortality was found to be linear until a cortisol concentration, following a dexamethasone suppression test, of 200 nmol/L.
Evidence Rating Level: 2 (Good)
Study Rundown: Patients with incidentally detected adrenal lesions, or adrenal incidentalomas (AIs), often exhibit autonomous cortisol secretion (ACS) despite a lack of overt Cushing syndrome. Severe hypercortisolism has been strongly linked to increased mortality; however, the extent to which mortality risk is increased in patients with AIs remains unclear. This study investigated the relationship between the degree of ACS, based on plasma cortisol level following an overnight dexamethasone suppression test (cortisolDST), and mortality. Compared to patients in the group with the lowest cortisol concentration, those in the two highest groups had a twofold and threefold increase, respectively, in mortality within 5 to 10 years. The study was limited by the results were not based on verified autonomous cortisol secretion, therefore, the association between cortisol secretion and mortality may be underestimated. Nonetheless, the study’s findings are significant as they implicated ACS as a potentially underappreciated risk factor for death that should be considered during treatment planning for patients with AIs.
In-Depth [retrospective cohort]: This retrospective study utilized data from all 1,048 patients from two hospitals in southern Sweden. Patients included in the study were at least 18 years of age with a previously unknown AI and were referred to the departments of endocrinology at the two hospitals. Patients living outside the catchment areas of the two hospitals were not included in the study. All patients were administered one milligram of dexamethasone followed by a blood sample collection for cortisol nine hours later. Patients were sorted into one of four groups based on cortisolDST: <50 nmol/L, 50–82 nmol/L, 83–137 nmol/L, and ≥138 nmol/L. The primary outcome was all-cause mortality. During a median follow-up of 6.38 years, 170 patients (16.2%) died. After adjusting for predefined covariates, patients with cortisolDST of 83 nmol/L and higher had a two- to three-fold increase in all-cause mortality compared to a cortisolDST below 50 nmol/L. Specifically, the hazard ratio (HR) for the 83–137 nmol/L group was 2.33 (95% confidence interval [CI], 1.53 to 3.53) and 2.87 (95% CI, 1.74 to 4.74) for the ≥138 nmol/L group. No difference in all-cause mortality was detected between the 50–82 nmol/L and <50 nmol/L groups during the study (HR, 1.17; 95% CI, 0.79 to 1.73). Cardiovascular disease was the only statistically significant contributor to increased mortality among the >83 nmol/L composite group (HR, 2.33; 95% CI, 1.27 to 4.28). Furthermore, mortality was independent of AI size, bilateralism, and basal corticotropin level; however, it was associated with dehydroepiandrosterone level (HR for DHEAS <1.04 umol/L, 1.47; 95% CI, 1.05 to 2.05). Overall, patients with moderately or severely elevated cortisol levels following a dexamethasone suppression test had an increased mortality risk.
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