Selecting the Appropriate Screening Test

This video segment focuses on the appropriate screening tests for hypercortisolism and the diagnostic workup process. Three initial screening tests are available, with the one milligram overnight dexamethasone suppression test being the most sensitive first-line option. This test involves the patient taking one milligram of dexamethasone before 11 PM, followed by plasma cortisol measurement the next morning before 9 AM, ideally at 8 AM. A cortisol level greater than 1.8 µg /dL indicates hypercortisolism. Importantly, dexamethasone levels should also be measured (cutoff greater than 140 ng/dL) to exclude false positives, which can occur in up to 20% of diabetic patients. The other screening options include 24-hour urinary free cortisol and late-night salivary cortisol measurements, both requiring 2 or 3 samples for reliability, though these have lower specificity in patients with type 2 diabetes.

Following positive screening results, ACTH levels and imaging studies become crucial for determining the underlying cause. ACTH measurements help differentiate between ACTH-dependent and ACTH-independent causes. Suppressed ACTH levels (below 10 picograms per milliliter) indicate ACTH-independent disease, where adrenal glands overproduce cortisol autonomously, suppressing pituitary ACTH release through negative feedback. Normal or elevated ACTH levels (greater than 10 pg/mL) suggest ACTH-dependent causes, such as Cushing disease from pituitary adenomas or ectopic Cushing syndrome from tumors in other organs like lungs or pancreas.

Imaging studies help anatomically localize the source of excess hormone production. For ACTH-independent causes, adrenal CT scans identify adrenal pathology, including incidental findings discovered during unrelated imaging studies. For ACTH-dependent causes, pituitary MRI is the primary imaging modality to detect pituitary adenomas, while whole-body imaging (chest and abdominal CT) screens for ectopic ACTH sources. Additionally, dehydroepiandrosterone sulfate (DHEAS) levels can support the diagnostic workup by helping differentiate between ACTH-dependent and independent causes, with low or low-normal DHEAS levels in conjunction with suppressed ACTH suggesting ACTH-independent hypercortisolism.