Subclinical hypercortisolism & DHEAs

Cortisol, produced by adrenal glands, is central to human physiology. It helps maintain proper blood pressure, glucose metabolism and electrolyte homeostasis, among other processes. Its direct involvement is also seen in the fight or flight response.

However when abnormally high, it can lead to detrimental health issues, best summarized in Cushing’s syndrome. Although Cushing’s syndrome is rare, subtle cortisol elevations are not. Recent research indicates that slight to moderate rise in cortisol could also lead to weight gain, diabetes, hypertension and bone fractures.

Currently the gold standard measure for subtle hypercortisolism is overnight low dose dexamethasone suppression test due to high sensitivity >99%. This original article identifies serum DHEAs as a better test due to the same sensitivity but improved specificity. The study was done in patients with adrenal mass of unknown significance, more properly termed adrenal incidentalomas.


J  C  E  M

Original Study

March 2017

Context: Subclinical hypercortisolism occurs in 5-30% of adrenal incidentalomas. Common screening tests for ACTH-independent hypercortisolism have substantial false-positive rates, mandating further time and resource-intensive investigations.

Objective: To determine whether low basal dehydroepiandrosterone sulfate (DHEAS) is a sensitive and specific screening test for subclinical hypercortisolism in adrenal incidentalomas.

Setting and Patients: In total, 185 patients with adrenal incidentalomas were screened for adrenal medullary (plasma metanephrines) and cortical [1 mg overnight dexamethasone suppression test (ONDST), 24-hour urinary free cortisol (UFC), serum DHEAS, plasma renin, and aldosterone] hyperfunction. Positive ONDST [≥1.8 mcg/dL] and/or UFC (more than the upper limit of reference range) results were further investigated. We diagnosed subclinical hypercortisolism when at least 2 of the following were met: raised UFC, raised midnight serum cortisol, 48-hour dexamethasone suppression test (DST) cortisol ≥1.8 mcg/dL.

Results: 29 patients (16%) were diagnosed with Subclinical hypercortisolism. ACTH was <10 pg/mL in all patients with subclinical hypercortisolism. We calculated age- and sex-specific DHEAS ratios (derived by dividing the DHEAS by the lower limit of the respective reference range) for all patients. Receiver operating characteristic curve analyses demonstrated that a DHEAS ratio of 1.12 was sensitive (>99%) and specific (91.9%) for the diagnosis of subclinical hypercortisolism. Cortisol following 1 mg ONDST of 1.9 mcg/dL was a sensitive (>99%) screening test for subclinical hypercortisolism but had lower specificity (82.9%). The 24-hour UFC lacked sensitivity (69%) and specificity (72%).

Conclusion: A single basal DHEAS measurement offers comparable sensitivity and greater specificity to the existing gold-standard 1 mg DST for the detection of subclinical hypercortisolism in patients with adrenal incidentalomas.