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 (cortisol; <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 cortisol less than 50 nmol/L, a cortisol 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 cortisol of 83 to 137 nmol/L ( = 119) had an HR of 2.30 (CI, 1.52 to 3.49), and a cortisol of 138 nmol/L or higher ( = 82) had an HR of 3.04 (CI, 1.86 to 4.98). Analyses using restricted cubic splines indicated that the association between cortisol and mortality was linear up to a cortisol 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 cortisol increased linearly until cortisol reached 200 nmol/L. A cortisol of 83 to 137 nmol/L was associated with a 2-fold increase in mortality, and a cortisol 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.