Should a dexamethasone suppression test (DST) be done in a 39-year-old female with fatigue and weight gain, and an adrenocorticotropic hormone (ACTH) level of 6 and a cortisol level of 18.9?

Dexamethasone Suppression Test in a 39-Year-Old Female with Fatigue, Weight Gain, and Abnormal Hormone Levels

A dexamethasone suppression test (DST) should be performed in this 39-year-old female with fatigue, weight gain, ACTH of 6, and cortisol of 18.9, as these findings suggest possible Cushing's syndrome with ACTH-independent hypercortisolism.

Interpretation of Initial Laboratory Values

The patient's presentation requires careful analysis of the available hormone values:

• Cortisol level of 18.9: This is elevated for most reference ranges (assuming μg/dL units), suggesting hypercortisolism
• ACTH level of 6: This is low or in the low-normal range (assuming pg/mL units), indicating potential ACTH-independent cortisol excess

These findings create a concerning pattern:

• Low/low-normal ACTH with elevated cortisol suggests autonomous cortisol production
• The clinical symptoms of fatigue and weight gain align with potential hypercortisolism

Diagnostic Algorithm for Suspected Cushing's Syndrome

Step 1: Initial Screening Tests

Based on current guidelines, the following tests are recommended for initial screening when Cushing's syndrome is suspected 1:

• Dexamethasone Suppression Test (DST): Recommended as the preferred test for this patient
• Late-night salivary cortisol (LNSC): Alternative option if available
• 24-hour urinary free cortisol (UFC): Consider if DST is contraindicated

Step 2: Determine the Source of Hypercortisolism

If DST confirms hypercortisolism, the next step is to determine the source:

• Low ACTH with elevated cortisol: Suggests ACTH-independent Cushing's syndrome (adrenal source)
• Normal/high ACTH with elevated cortisol: Would suggest ACTH-dependent Cushing's syndrome

Rationale for Performing DST

1. Pattern Recognition: The combination of low ACTH with elevated cortisol strongly suggests adrenal-dependent Cushing's syndrome, which requires confirmation 1

2. Guideline Recommendations: Current endocrine guidelines recommend DST as a first-line test for confirming hypercortisolism when clinical suspicion exists 1

3. Differential Diagnosis: DST helps distinguish true Cushing's syndrome from pseudo-Cushing's states that can present with similar symptoms 1

DST Protocol

For this patient, the recommended DST protocol is:

• Low-dose DST (LDDST): 0.5 mg dexamethasone every 6 hours for 48 hours
• Overnight DST: Alternative option using 1 mg dexamethasone at 11 PM with 9 AM cortisol measurement the next day
• Interpretation: Failure to suppress cortisol to <1.8 μg/dL (50 nmol/L) suggests Cushing's syndrome 1

Important Considerations and Pitfalls

• False positives: Can occur with estrogen therapy, medications affecting dexamethasone metabolism, severe stress, depression, alcoholism, and obesity 1

• Measuring dexamethasone levels: Consider measuring dexamethasone levels if a false-positive result is suspected due to altered dexamethasone metabolism 1

• Cyclic Cushing's syndrome: May require repeated testing during symptomatic periods 1

• Secondary adrenal insufficiency: The patient's presentation could alternatively represent secondary adrenal insufficiency, which would also require evaluation with ACTH stimulation testing 2

Next Steps After DST

If DST confirms hypercortisolism:

1. Adrenal imaging (CT or MRI) to identify potential adrenal adenoma or other lesions
2. Consider additional testing to confirm the diagnosis
3. Endocrinology referral for specialized management

Conclusion

The combination of fatigue, weight gain, low ACTH, and elevated cortisol warrants a DST to confirm or exclude Cushing's syndrome. This approach aligns with current endocrine guidelines and addresses the most likely pathophysiology suggested by the laboratory values.