What are the screening questions for Cushing's syndrome?

From the Guidelines

Screening for Cushing's syndrome involves asking patients about key symptoms and risk factors, and the most recent and highest quality study recommends using a combination of clinical evaluation and biochemical tests, such as 24-hour urinary free cortisol, late-night salivary cortisol, or overnight dexamethasone suppression tests, to confirm the diagnosis 1. When evaluating patients for Cushing's syndrome, it is essential to consider the following key symptoms and risk factors:

• Unexplained weight gain, particularly in the face (moon facies), trunk, and back of neck (buffalo hump), while limbs remain thin
• Easy bruising, thin skin, purple stretch marks (striae), muscle weakness, fatigue, and mood changes like depression or irritability
• Recent onset of hypertension, diabetes, or osteoporosis that seems disproportionate to age and risk factors
• Menstrual irregularities, excess facial/body hair growth, and acne in women
• Decreased libido and erectile dysfunction in men
• Use of glucocorticoid medications, such as prednisone, which can cause iatrogenic Cushing's syndrome The timing and progression of symptoms help distinguish Cushing's from other conditions, as it typically develops gradually over months to years. According to the most recent study, the recommended protocol for diagnosis of Cushing disease includes:
• 24-hour urinary free cortisol (UFC) excretion for 3 days, with a diagnostic cut-off of >193 nmol/24 h (>70 μg/m2) 1
• Late-night salivary cortisol, with a diagnostic cut-off based on local assay cut-off 1
• Overnight dexamethasone suppression test, with a diagnostic cut-off of >=50 nmol/l (>=1.8 μg/dl) 1 The use of these biochemical tests, in combination with clinical evaluation, is crucial for accurate diagnosis and management of Cushing's syndrome, and can help reduce morbidity, mortality, and improve quality of life for patients 1.

From the Research

Cushing's Syndrome Screening Tests

The following are some of the screening tests used to diagnose Cushing's syndrome:

• 1-mg dexamethasone suppression test (DST) 2, 3, 4
• Late-night salivary cortisol (LNSC) measurement 5, 3, 4
• 24-hour urinary free cortisol (UFC) measurement 2, 3, 4

Characteristics of Each Test

• The 1-mg DST is a simple dynamic test that explores the normal feedback reaction from the hypothalamic-pituitary-adrenal axis (HPA) 4
• LNSC measurement is a simple and reliable screening test for spontaneous Cushing's syndrome, and can also be used to evaluate suspected intermittent hypercortisolism 5
• UFC measurement reflects the integrated tissue exposure to free cortisol over 24 hours, and provides a particular picture of endogenous hypercortisolism 4

Diagnostic Performance of Each Test

• The 1-mg DST has a high specificity (97%) and sensitivity (100%) for diagnosing Cushing's syndrome 3
• LNSC measurement has a sensitivity of 92% and a specificity of 89% for diagnosing Cushing's syndrome 5
• UFC measurement has a high sensitivity (97%) and specificity (91%) for diagnosing Cushing's syndrome, and is considered to be at least as good as other combinations of tests 3

Pitfalls and Limitations of Each Test

• The 1-mg DST can be affected by certain drugs, and false-positive results can occur 4
• LNSC measurement can be affected by inadequate soaking of the device or cyclic Cushing's syndrome 4
• UFC measurement requires complete urine collections with appropriate total volumes, and can be affected by cross-reactivity between cortisol, cortisone, and other metabolites 4