What is the initial screening process for patients suspected of having Cushing's syndrome?

Initial Screening Process for Cushing's Syndrome

The initial screening for patients suspected of having Cushing's syndrome should include three first-line tests: 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), and/or the overnight 1mg dexamethasone suppression test (DST). 1

Clinical Suspicion: When to Screen

Before initiating biochemical testing, it's crucial to determine if the clinical presentation warrants screening:

High-Suspicion Clinical Features:

• Unusual fat distribution (face, neck, trunk)
• Purple/livid striae (especially if >1cm wide)
• Proximal muscle weakness
• Easy bruising
• Thin, vulnerable skin
• Osteoporotic fractures in young patients
• Unexplained weight gain with decreasing height in children

Important: First Rule Out Exogenous Causes

• Determine if the patient is taking any form of glucocorticoids (oral, injections, inhalers, topical)
• If yes, stop glucocorticoids if possible before testing 1

Screening Algorithm

1. Assess clinical likelihood of endogenous Cushing's syndrome

   • Low probability → Consider not testing
   • Intermediate or high probability → Proceed with 2-3 screening tests

2. First-line screening tests (select based on patient circumstances):

   • 24-hour urinary free cortisol (UFC) collection (≥2 measurements)
   • Late-night salivary cortisol (LNSC) (≥2 measurements)
   • Overnight 1mg dexamethasone suppression test (DST)

3. Interpretation of results:

   • If normal → Cushing's syndrome unlikely
   • If abnormal → Repeat 1-2 screening tests to confirm
   • If discordant results → Consider cyclic Cushing's or periodically re-evaluate 1

Test Selection Considerations

24-hour Urinary Free Cortisol (UFC)

• Collect 2-3 specimens
• Advantages: Integrates cortisol production over 24 hours
• Limitations: Requires proper collection; false positives with high fluid intake; false negatives with renal impairment

Late-Night Salivary Cortisol (LNSC)

• Collect ≥2 specimens on consecutive days
• Advantages: Easy collection; reflects loss of circadian rhythm; high sensitivity
• Limitations: Affected by contamination, smoking, bleeding gums

Overnight 1mg Dexamethasone Suppression Test

• Advantages: Simple outpatient procedure; high sensitivity (98.1%)
• Limitations: False positives with medications affecting dexamethasone metabolism; estrogen-containing contraceptives can alter results
• Consider measuring dexamethasone level along with cortisol to improve test interpretation 1

Common Pitfalls and Caveats

1. Avoid testing in conditions that can cause false positives ("pseudo-Cushing's states"):

   • Severe obesity
   • Uncontrolled diabetes
   • Pregnancy
   • Polycystic ovary syndrome (PCOS)
   • Depression/psychiatric disorders
   • Alcoholism
   • Physical stress (illness/surgery)
   • Excessive exercise 1

2. Medication interference:

   • Review all medications that might affect test results
   • Estrogen-containing oral contraceptives can affect DST results
   • Certain drugs can accelerate dexamethasone metabolism (phenytoin, phenobarbital)

3. Cyclical Cushing's syndrome:

   • Consider this possibility if clinical suspicion is high but tests are normal
   • May require periodic re-evaluation 1

Next Steps After Positive Screening

If screening tests confirm hypercortisolism:

1. Measure plasma ACTH to determine if Cushing's syndrome is ACTH-dependent or ACTH-independent
2. Further testing based on ACTH results:
   • Low ACTH → Adrenal imaging (CT or MRI)
   • Normal/high ACTH → Pituitary MRI 1

Remember that no single test has 100% diagnostic accuracy, and the diagnosis of Cushing's syndrome often requires multiple tests to confirm hypercortisolism before proceeding to determine its etiology.