Cyclic Cushing's Syndrome Diagnosis and Management

Introduction to Cyclic Cushing's Syndrome

Normal urinary free cortisol (UFC) levels in a patient with suspected ACTH-dependent cyclic Cushing's syndrome despite large urine volume (3-4L) are likely due to the cyclical nature of the condition, where periods of normal cortisol production alternate with hypercortisolism, as noted by The Lancet Diabetes and Endocrinology 1

The Endocrine Society recommends obtaining multiple UFC measurements, late-night salivary cortisol (LNSC), and dexamethasone suppression tests (DST) for suspected cyclic Cushing's syndrome, with at least two or three UFC collections to evaluate variability, according to The Lancet Diabetes and Endocrinology and Nature Reviews Endocrinology 1, 3
Dynamic testing and localization testing should be preceded by confirmatory tests to document the active phase in classical cyclic Cushing's disease or in patients with unpredictable fluctuating cortisol levels, as recommended by The Lancet Diabetes and Endocrinology 1

DST may be the preferred test for shift workers and patients with disrupted circadian rhythm due to uneven sleep schedules, as suggested by The Lancet Diabetes and Endocrinology 1
The desmopressin test has high specificity for Cushing's disease and is less complex and expensive than the Dex-CRH test, according to The Lancet Diabetes and Endocrinology 1
For suspected cyclic Cushing's syndrome with normal UFC despite clinical suspicion, repeated UFC measurements over time, late-night salivary cortisol tests, and DST during suspected active phases of the disease are recommended, as noted by The Lancet Diabetes and Endocrinology and Praxis Medical Insights 1, 2, 5

Don't rely on a single normal UFC result to rule out cyclic Cushing's syndrome, as cautioned by Praxis Medical Insights 2
Be aware that bilateral inferior petrosal sinus sampling (IPSS) should not be performed to diagnose hypercortisolism, as the central-to-peripheral ACTH gradient in healthy controls and pseudo-Cushing's overlaps with Cushing's disease, according to The Lancet Diabetes and Endocrinology 1