Diagnosis of Cushing's Disease

Diagnostic Approach

The American College of Cardiology recommends excluding the use of exogenous corticosteroids, followed by 2-3 screening tests: 24-hour urinary free cortisol, nocturnal salivary cortisol, and/or 1 mg dexamethasone suppression test to diagnose Cushing's disease 1
The Endocrine Society suggests that a lack of suppression of morning cortisol (<1.8 μg/dL or <50 nmol/L) after administering 1 mg of dexamethasone at midnight confirms hypercortisolism 1
Elevated 24-hour urinary free cortisol confirms excessive cortisol production 2
Loss of normal circadian rhythm of cortisol, with elevated values suggesting hypercortisolism, can be detected by nocturnal salivary cortisol test 1

The European Society of Hypertension notes that classic signs of Cushing's disease include changes in skin, such as facial plethora, easy bruising, purple striae, and fragile skin, which are associated with hypercortisolism 3
Redistribución of fat, including central obesity, buffalo hump, and supraclavicular fat, is a common feature of Cushing's disease 3
Metabolic manifestations, such as hyperglycemia, glucose intolerance, and hypertension (present in >80% of cases), are frequently observed in patients with Cushing's disease 3

Measuring plasma ACTH can differentiate between ACTH-dependent (60-85%) and ACTH-independent (15-20%) causes of hypercortisolism 2
Suppressed ACTH suggests an adrenal source (adenoma or carcinoma) 2
Normal or high ACTH indicates Cushing's disease (pituitary adenoma) or ectopic ACTH syndrome 2

Although hypertension is common (>80%) in patients with Cushing's syndrome, Cushing's syndrome is a rare cause of resistant hypertension, with no cases found in a study of 423 individuals with resistant hypertension 3