Mortality in Modest Autonomous Cortisol Secretion

Jun 02, 2021
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Authors:
Kjellbom A, Lindgren O, Puvaneswaralingam S, et al.
Citation:
Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas: A Cohort Study. Ann Intern Med 2021;May 25:[Epub ahead of print].
Summary By:
Debabrata Mukherjee, MD, FACC

Quick Takes

  • The relationship between cortisolDST and mortality is fairly linear up to a cortisolDST of 200 nmol/L.
  • Furthermore, a cortisolDST between 83 and 137 nmol/L was associated with a doubling in risk for death and a cortisolDST of 138 nmol/L or higher with a threefold increase in risk.
  • At this time, aggressive treatment of known cardiovascular risk factors in these patients is indicated and thoughtful consideration of these results is needed in selecting patients for adrenalectomy.

Study Questions:

What is the association between mortality and levels of autonomous cortisol secretion in patients with adrenal incidentalomas?

Methods:

The investigators conducted a retrospective cohort study (ClinicalTrials.gov: NCT03919734) at two hospitals in southern Sweden. Consecutive patients who had adrenal incidentalomas identified between 2005 and 2015 were followed for up to 14 years. Outcome data were collected from national registers. Patients were grouped according to plasma cortisol level after a 1-mg dexamethasone suppression test (cortisolDST; <50, 50-82, 83-137, or ≥138 nmol/L). The primary outcome was all-cause mortality but investigators also studied cause-specific mortality, such as from cardiovascular disease, cancer, infection, or other diseases. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and adjusted cumulative incidence.

Results:

During a median follow-up of 6.4 years, 170 of 1,048 patients died. Compared with a cortisolDST of <50 nmol/L, a cortisolDST of 50-82 nmol/L was not associated with increased mortality (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.78-1.70). However, a cortisolDST of 83-137 nmol/L (n = 119) had an HR of 2.30 (95% CI, 1.52-3.49), and a cortisolDST of 138 nmol/L or higher (n = 82) had an HR of 3.04 (95% CI, 1.86-4.98). Analyses using restricted cubic splines indicated that the association between cortisolDST and mortality was linear up to a cortisolDST of 200 nmol/L.

Conclusions:

The authors concluded that the association between mortality and cortisolDST increased linearly until cortisolDST reached 200 nmol/L.

Perspective:

This cohort study reports that the relationship between cortisolDST and mortality is fairly linear up to a cortisolDST of 200 nmol/L. Furthermore, a cortisolDST between 83 and 137 nmol/L was associated with a doubling in risk for death and a cortisolDST of 138 nmol/L or higher with a threefold increase in risk. The increase in mortality associated with cortisolDST values of 83 nmol/L or higher implies the need for vigilant medical therapy for risk factors and possibly broadening the indications for adrenalectomy, although no evidence of beneficial effects on mortality currently exists. At this time, aggressive treatment of known cardiovascular risk factors in these patients is indicated and thoughtful consideration of these results is needed in selecting patients for adrenalectomy.

Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Prevention

Keywords: Adrenal Gland Neoplasms, Adrenalectomy, Bodily Secretions, Cardiovascular Diseases, Dexamethasone, Hydrocortisone, Metabolic Syndrome, Myocardial Ischemia, Neoplasms, Plasma, Primary Prevention, Risk Factors


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