Cortisol Level and Dexamethasone Suppression Test Improve Disease Analysis

Adrenal masses and people who may have Cushing syndrome are often evaluated with a dexamethasone suppression test (DST), but false positives occur. Researchers examined whether free cortisol assessment during DST would aid in diagnosis.

Evaluation of free cortisol levels during a post–dexamethasone suppression test (DST) may more accurately diagnose disease in patients who have adequate dexamethasone concentrations combined with post-DST total cortisol levels between 1.8 and 5 mcg/dL, according to a study in the Journal of Clinical Endocrinology & Metabolism.

Researchers sought to determine the usefulness of free cortisol assessment during DST. The cross-sectional study was conducted between January 2016 and August 2018 in adults ≥18 years of age. Participants were consecutively recruited from an endocrinology clinic and divided into two groups: healthy volunteers without adrenal disorders and patients who were being assessed for cortisol excess for clinical reasons. All participants underwent DST with measurements of total and free cortisol and dexamethasone concentrations.

The healthy cohort included 168 volunteers without adrenal disorders (median age, 29.5 years; 67% women, of whom 42% were using oral contraceptive therapy [OCP]). There were 196 patients undergoing evaluation for hypercortisolism (median age, 57 years, 67% women, of whom 10% were using OCP). Oral contraceptive therapy is known to potentially affect corticosteroid-binding globulin concentrations, which may lead to either falsely low or high total cortisol concentrations and affect the diagnosis of adrenal insufficiency or hypercortisolism. Pregnancy, liver, and renal failure, and several medications, may also affect test results. 

Most patients had adequate dexamethasone concentrations (≥0.1 mcg/dL), which suggests optimal compliance and absorption/metabolism of dexamethasone. Rates were similar to those of healthy volunteers (96.3% and 97.6%, respectively; P = .56).

Among the women volunteers using OCP, 25.5% had abnormal post-DST total cortisol (>1.8 mcg/dL). The post-DST free cortisol maximum level was ≤48 ng/dL for men and for women who were not using OCP, and ≤79 ng/dL for women using OCP.

A total of 24 (12.7%) patients showed a discordance between post-DST total and free cortisol; 19 patients (21%) had abnormal post-DST total cortisol but had post-DST free cortisol in the reference range (false-positive results). Oral contraceptive therapy use was the only patient characteristic associated with this discordance (21.1% in the false-positive group vs 4.7%, P = .02).

Post-DST total cortisol had a diagnostic accuracy of 87.3% (95% CI, 81.7-91.7) compared with the post-DST free cortisol concentrations.

Study limitations include the single-institution design at a referral center, which led to inclusion of a higher proportion of patients with hypercortisolism than would normally be observed in a primary setting). In addition, the volunteer cohort was not assessed with a full battery of testing for hypercortisolism and was younger than the patient cohort.

“We suggest a sequential approach to DST in clinical practice,” the researchers advised. “After providing optimal instructions, we propose that DST is performed in patients suspected to have cortisol excess regardless of special circumstances, such as OCP use.”

Disclosure: At least one study author declared affiliations with pharmaceutical companies. Please see the original reference for a full list of authors’ disclosures. 


Genere N, Kaur RJ, Athimulam S, et al. Interpretation of abnormal dexamethasone suppression test is enhanced with use of synchronous free cortisol assessment. J Clin Endocrinol Metab. Published online October 14, 2021. doi: 10.1210/clinem/dgab724