From the Guidelines
The initial tests for diagnosing Cushing's syndrome in a primary care office should include either urinary free cortisol (UFC) and/or late-night salivary cortisol (LNSC) test, with the dexamethasone suppression test (DST) being an alternative option if LNSC is not feasible. According to the most recent guideline update 1, if Cushing's disease is suspected, starting with either UFC and/or LNSC is recommended, as these tests can help identify patients with excess cortisol production. The UFC test involves collecting all urine over a 24-hour period to measure cortisol excretion, while the LNSC test involves collecting saliva samples between 11 PM and midnight on two separate occasions to assess cortisol levels.
For patients suspected of having Cushing's syndrome due to an adrenal tumor, the guideline recommends starting with the DST 1. The DST involves administering 1 mg of dexamethasone orally at 11 PM, followed by a blood cortisol measurement at 8 AM the next morning. Measuring dexamethasone level along with cortisol the morning after 1 mg dexamethasone ingestion can improve test interpretability 1.
It's essential to note that at least two different tests should be performed to confirm the diagnosis, as false positives can occur with certain conditions such as obesity, depression, and alcoholism 1. The choice of test may also depend on patient-specific factors, such as shift work or the use of estrogen-containing oral contraceptives, which can affect test results 1.
In terms of diagnostic cut-offs, the guideline suggests using a UFC excretion of >193 nmol/24 h (>70 μg/m2) for confirmation of Cushing's syndrome, with a sensitivity of 89% and specificity of 100% 1. For the LNSC test, the cut-off value may vary depending on the local assay, but a level >0.2 μg/dL is generally considered indicative of Cushing's syndrome.
Overall, the selection of initial tests for diagnosing Cushing's syndrome in a primary care office should be guided by the most recent clinical guidelines and should take into account patient-specific factors and the potential for false positives. If screening tests are positive, referral to an endocrinologist is necessary for confirmatory testing and determining the specific cause of Cushing's syndrome.
From the Research
Initial Tests for Diagnosing Cushing's Syndrome
The initial tests for diagnosing Cushing's syndrome in a primary care office include:
- Overnight dexamethasone suppression test
- Low-dose dexamethasone suppression test
- Measurement of basal state plasma adrenocorticotropin (ACTH) levels
- Measurement of urinary free cortisol (UFC) excretion
Dexamethasone Suppression Tests
The dexamethasone suppression tests are used to diagnose and differentiate Cushing's syndrome. The tests include:
- Overnight 8 mg dexamethasone suppression test: This test has a sensitivity of 92% and a specificity of 100% for diagnosing Cushing's disease 2
- 0.5 mg dexamethasone suppression test: This test has a sensitivity of 99.1% and a specificity of 98.4% for diagnosing ACTH-dependent Cushing's syndrome 3
- Very high dose dexamethasone suppression test (32 mg): This test is used for differential diagnosis of Cushing's syndrome and has been shown to be superior to the 8 mg test in some cases 4
Other Diagnostic Tests
Other diagnostic tests that may be used to diagnose Cushing's syndrome include:
- Measurement of plasma cortisol levels: This test can be used to diagnose Cushing's syndrome, but it is not as sensitive as the dexamethasone suppression tests 5
- Insulin tolerance test: This test can be used to diagnose Cushing's syndrome, but it is not as commonly used as the dexamethasone suppression tests 5
- Metyrapone test: This test can be used to diagnose Cushing's syndrome, but it is not as commonly used as the dexamethasone suppression tests 5
Recommendations
Based on the available evidence, the 0.5 mg dexamethasone suppression test is recommended as an initial screening test for diagnosing ACTH-dependent Cushing's syndrome 3. The overnight 8 mg dexamethasone suppression test is also a useful test for diagnosing Cushing's disease 2, 6. The very high dose dexamethasone suppression test (32 mg) may be used for differential diagnosis of Cushing's syndrome in cases where the 8 mg test is not suppressible 4.