Screening in Primary Care: When and How to Use the Overnight Dexamethasone Suppression Test

In this segment, Richard Auchus, MD, and Ralph DeFronzo, MD, examine why hypercortisolism remains underdiagnosed in the settings where most patients receive care—busy primary care and cardiology clinics. Dr DeFronzo points out that primary care physicians, seeing patients every 10 to 15 minutes, manage numerous individuals with “routine” but difficult-to-control type 2 diabetes on three or more oral agents, basal and prandial insulin, multiple antihypertensive drugs, and often antidepressants. Although these clinicians were trained to recognize only the florid Cushing phenotype, the speakers stress that a meaningful proportion of such patients actually have underlying cortisol excess contributing to their metabolic resistance.

To address this gap, Dr DeFronzo advocates for a simple, standardized screening strategy anchored by the overnight 1-mg dexamethasone suppression test (DST). Patients take 1 mg of dexamethasone at approximately 23:00 and present the following morning for a blood draw. In a normal hypothalamic-pituitary-adrenal axis, serum cortisol should suppress to less than 1.8 µg/dL; values above this threshold constitute a positive screen. The test’s simplicity—one inexpensive tablet and a single morning cortisol measurement—makes it feasible for routine clinical practice. Concurrent measurement of dexamethasone confirms that the patient actually ingested the dose and that pharmacologic exposure is adequate.

Following an abnormal DST, Dr Auchus describes a rational next step: characterization of the etiology. In patients with suspected pituitary Cushing disease, late-night salivary cortisol and 24-hour urinary free cortisol (UFC) may document loss of circadian rhythm and increased cortisol production. However, Dr Auchus cautions that UFC is relatively insensitive, particularly early in the disease course, because cortisol must exceed binding capacity to appear in the urine. Additionally, late-night salivary cortisol tends not to be elevated in ACTH-independent forms, such as adrenal adenomas and nodular hyperplasia, for which the DST remains the most sensitive initial test. This segment equips clinicians with a practical algorithm that begins with a single, easy-to-implement screening tool and then proceeds to more focused evaluation based on suspected disease subtype.