What are the next steps in managing a patient with suspected Cushing's syndrome after a post-dexamethasone (cortisol suppression test) suppression test and elevated 24-hour urinary cortisol?

Next Steps After Positive Dexamethasone Suppression Test and Elevated Urinary Cortisol

The next step for a patient with AM cortisol of 2.85 after 1mg overnight dexamethasone suppression test and elevated 24-hour urinary cortisol is to measure plasma ACTH levels to determine if the Cushing's syndrome is ACTH-dependent or ACTH-independent. 1, 2

Diagnostic Algorithm

1. Confirm Cushing's Syndrome

• The patient already has two positive screening tests:
  • Elevated 24-hour urinary free cortisol 1
  • Failed overnight 1mg dexamethasone suppression test (cortisol 2.85, which is >1.8 μg/dL cutoff) 1, 2
• This combination strongly suggests Cushing's syndrome 2, 3

2. Determine ACTH Dependency

• Measure plasma ACTH levels 1, 2
  • If ACTH is low (<5 ng/L): ACTH-independent Cushing's syndrome (adrenal source) 2
  • If ACTH is normal or elevated (≥5 ng/L): ACTH-dependent Cushing's syndrome (pituitary or ectopic source) 2

3. Further Evaluation Based on ACTH Results

For ACTH-Independent Cushing's Syndrome:

• Perform adrenal CT or MRI to identify adrenal lesion(s) 1, 2
• Look for adrenal adenoma, carcinoma, or bilateral hyperplasia 2

For ACTH-Dependent Cushing's Syndrome:

• Perform pituitary MRI 1, 2
• Based on MRI findings:
  • If pituitary adenoma ≥10 mm: Presumed Cushing's disease 1
  • If pituitary adenoma 6-9 mm: Consider CRH stimulation test 1
  • If no adenoma or <6 mm lesion: Perform bilateral inferior petrosal sinus sampling (BIPSS) 1, 2

Important Considerations

• Measure dexamethasone levels along with cortisol during dexamethasone suppression testing to improve test interpretability and rule out abnormal dexamethasone metabolism 2

• Consider cyclic Cushing's syndrome if test results are inconsistent, which may require periodic re-evaluation 2, 3

• Be aware of potential false positives in screening tests due to:

  • Severe obesity 1, 2
  • Alcoholism 2
  • Uncontrolled diabetes mellitus 1
  • Psychiatric conditions 4

• For ACTH-dependent Cushing's syndrome with inconclusive MRI, BIPSS is the gold standard for differentiating between pituitary and ectopic sources 2, 4

• The diagnostic approach should be systematic and thorough, as mischaracterization can lead to inappropriate management strategies and poor outcomes 2, 5