What is the diagnosis protocol for hyperadrenocorticism (Cushing's syndrome) or conditions characterized by excessive adrenal hormone production?

From the Guidelines

The diagnosis protocol for hyperadrenocorticism (Cushing's syndrome) or conditions characterized by excessive adrenal hormone production involves a combination of clinical suspicion, laboratory tests, and imaging studies.

Key Steps in Diagnosis

• Clinical suspicion: The diagnosis of Cushing's syndrome (CS) often starts with a clinical suspicion based on signs and symptoms such as weight gain, central obesity, easy bruising, severe hypertension, diabetes, proximal muscle weakness, fatigue, depression, sleep disturbances, menstrual irregularities, and virilization (in females) or fragility fractures 1.
• Laboratory tests: The initial laboratory tests for CS include late night salivary cortisol (LNSC), overnight 1-mg dexamethasone suppression test (DST), and 24-hour urinary free cortisol (UFC) 1. These tests assess cortisol secretory status and can help identify abnormal circadian rhythm, impaired glucocorticoid feedback, and increased bioavailable cortisol.
• Imaging studies: Once the diagnosis of CS is confirmed, imaging studies such as adrenal CT or MRI and pituitary MRI are used to determine the cause of the excess cortisol production 1.

Specific Tests for Cushing's Syndrome

• 1 mg dexamethasone suppression testing: This is the preferred screening test for identifying autonomous cortisol secretion when clinically appropriate 1.
• UFC: This test measures the amount of cortisol in the urine over a 24-hour period and can help diagnose CS 1.
• LNSC: This test measures the level of cortisol in the saliva at night and can help diagnose CS 1.
• ACTH measurement: This test measures the level of adrenocorticotropic hormone (ACTH) in the blood and can help determine if the CS is ACTH-dependent or independent 1.

Additional Tests

• Dex-CRH test: This test can help distinguish between ACTH-dependent CS and pseudo-CS 1.
• Desmopressin test: This test can help diagnose CS and distinguish it from pseudo-CS 1.
• IPSS: This test can help diagnose ectopic CS or Cushing's disease (CD) 1.

Important Considerations

• Non-neoplastic hypercortisolism (pseudo-CS): This condition can mimic CS and should be considered in the differential diagnosis 1.
• Medications: Certain medications can interfere with laboratory test results and should be considered when interpreting test results 1.
• Clinical context: The clinical context, including the patient's medical history, physical examination, and laboratory test results, should be considered when diagnosing and managing CS 1.

From the Research

Diagnosis Protocol for Hyperadrenocorticism (Cushing's Syndrome)

The diagnosis protocol for hyperadrenocorticism (Cushing's syndrome) involves several steps to confirm the presence of excessive adrenal hormone production and to determine the underlying cause. The following are the key steps in the diagnosis protocol:

• Screening for elevated cortisol levels using a 24-hour urinary free cortisol test, late-night salivary cortisol test, or a dexamethasone suppression test 2, 3
• Evaluating plasma corticotropin levels to distinguish between adrenal causes of hypercortisolism and corticotropin-dependent forms of hypercortisolism 2
• Using imaging studies such as pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging to identify tumor sources of hypercortisolism 2, 4
• Performing dynamic tests such as the desmopressin stimulation test, midnight serum cortisol, and late-night salivary cortisol levels to differentiate between Cushing's syndrome and non-neoplastic hypercortisolism 5
• Using a step-by-step approach combining several diagnostic tools and a multidisciplinary evaluation in a referral center to diagnose ACTH-dependent hypercortisolism 6

Diagnostic Tests

The following diagnostic tests are used to diagnose hyperadrenocorticism (Cushing's syndrome):

• 24-hour urinary free cortisol test: measures the level of cortisol in the urine over a 24-hour period 2, 3
• Late-night salivary cortisol test: measures the level of cortisol in the saliva at night 2, 3
• Dexamethasone suppression test: measures the level of cortisol in the blood after administering dexamethasone 2, 3
• Desmopressin stimulation test: measures the level of cortisol in the blood after administering desmopressin 5
• Midnight serum cortisol: measures the level of cortisol in the blood at midnight 5
• Late-night salivary cortisol: measures the level of cortisol in the saliva at night 5

Imaging Studies

The following imaging studies are used to identify tumor sources of hypercortisolism:

• Pituitary magnetic resonance imaging: images the pituitary gland to detect tumors 2
• Bilateral inferior petrosal sinus sampling: measures the level of corticotropin in the blood from the petrosal sinuses to detect tumors 2, 4
• Adrenal or whole-body imaging: images the adrenal glands or the whole body to detect tumors 2, 4