Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas : A Cohort Study

BACKGROUND: Autonomous cortisol secretion in patients with adrenal incidentalomas is associated with increased mortality, but detailed information about the risk associated with specific levels of autonomous cortisol secretion is not available.OBJECTIVE: To measure the association between mortality and levels of autonomous cortisol secretion in patients with adrenal incidentalomas.DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT03919734).SETTING: Two hospitals in southern Sweden.PATIENTS: Consecutive patients who had adrenal incidentalomas identified between 2005 and 2015 and were followed for up to 14 years. Outcome data were collected from national registers.MEASUREMENTS: Patients were grouped according to plasma cortisol level after a 1-mg dexamethasone suppression test (cortisolDST; <50, 50 to 82, 83 to 137, or ≥138 nmol/L).RESULTS: During a median follow-up of 6.4 years, 170 of 1048 patients died. Compared with a cortisolDST less than 50 nmol/L, a cortisolDST of 50 to 82 nmol/L was not associated with increased mortality (hazard ratio [HR], 1.15 [95% CI, 0.78 to 1.70]). However, a cortisolDST of 83 to 137 nmol/L (n = 119) had an HR of 2.30 (CI, 1.52 to 3.49), and a cortisolDST of 138 nmol/L or higher (n = 82) had an HR of 3.04 (CI, 1.86 to 4.98). Analyses using restricted cubic splines indicated that the association between cortisolDST and mortality was linear up to a cortisolDST of 200 nmol/L.LIMITATION: The results are not based on verified autonomous cortisol secretion; thus, the association may be underestimated.CONCLUSION: The association between mortality and cortisolDST increased linearly until cortisolDST reached 200 nmol/L. A cortisolDST of 83 to 137 nmol/L was associated with a 2-fold increase in mortality, and a cortisolDST of 138 nmol/L or higher was associated with a 3-fold increase in mortality. Additional studies should be done, and until those studies are completed some clinicians may consider these findings when deciding which patients to recommend for surgery.PRIMARY FUNDING SOURCE: Lisa and Johan Grönberg Foundation and Gyllenstiernska Krapperup Foundation

ACTH following overnight dexamethasone suppression can be used in the verification of autonomous cortisol secretion in patients with adrenal incidentalomas

Objective: During the investigation of adrenal incidentalomas, it is important to accurately diagnose autonomous cortisol secretion (ACS) but the specificity of cortisol ≥50 nmol/L after overnight dexamethasone suppression (cortisolONDST) is low. Therefore, ACTH following overnight dexamethasone suppression (ACTHONDST) and cortisol following a 2-day dexamethasone suppression test (cortisol2-DAYDST) were examined as markers of HPA axis suppression during ONDST. Design: This cross-sectional study examined patients with adrenal incidentalomas and basal ACTH ≥ 2.0 pmol/L who underwent ONDST. Measurements: ACTHONDST/ACTH ratio (ACTH ratio) was calculated for all patients. To define cut-off levels for ACTHONDST and ACTH ratio as markers of HPA axis suppression, ROC curves were used to separate patients with cortisolONDST <50 and ≥50 nmol/L. Results: CortisolONDST was ≥50 nmol/L in 140 out of 373 patients. In patients with cortisolONDST <50 nmol/L, ACTHONDST was 0.28 pmol/L (<0.23–2.7). DHEAS was positively correlated to ACTHONDST, demonstrating a 9% increase with a doubling in ACTHONDST, p = 0.02. The best cut-off levels for ACTHONDST and ACTH ratio to detect cortisolONDST ≥50 nmol/L were ≥0.6 pmol/L and ≥18% respectively. These cut-off levels were tested on patients with cortisolONDST <50 nmol/L, considered to have adequate suppression (n = 233), and patients with reduction of ≥50 nmol/L from cortisolONDST to cortisol2-DAYDST, who were considered to have inadequate suppression (n = 16). ACTHONDST ≥0.6 pmol/L and ACTH ratio ≥18% had a sensitivity of 75% and 81% respectively, and a specificity of 78% and 85% respectively, for detecting patients with inadequate suppression. Conclusions: ACTHONDST and ACTH ratio can be markers of HPA axis suppression in the investigation of adrenal incidentalomas. CortisolONDST ≥50 nmol/L with ACTHONDST <0.6 pmol/L or ACTH ratio <18% should lead to the suspicion of ACS