What does an elevated dexamethasone level with low free cortisol indicate?

Interpretation of Elevated Dexamethasone with Low Free Cortisol

An elevated dexamethasone level with low free cortisol most likely indicates appropriate suppression of the hypothalamic-pituitary-adrenal (HPA) axis, ruling out Cushing's syndrome. 1, 2

Understanding the Dexamethasone Suppression Test (DST)

• The DST is a first-line screening test for Cushing's syndrome, with normal response being cortisol suppression below 50 nmol/L (1.8 μg/dL) 1
• In a properly functioning HPA axis, exogenous dexamethasone suppresses ACTH production, which in turn reduces cortisol secretion 2
• Measuring dexamethasone levels alongside cortisol can improve test interpretation by confirming adequate dexamethasone absorption 1

Clinical Interpretation of Results

• Elevated dexamethasone with suppressed cortisol indicates:

  • Normal negative feedback of the HPA axis 2
  • Effective absorption and metabolism of dexamethasone 3
  • Absence of Cushing's syndrome 1, 2

• This pattern is consistent with:

  • Normal adrenal function 4
  • Appropriate response to the dexamethasone suppression test 2
  • Exclusion of autonomous cortisol production 1

Potential Pitfalls in Interpretation

• False positive results (failure to suppress despite no Cushing's) can occur with:

  • Medications affecting dexamethasone metabolism (CYP3A4 inducers like phenobarbital, carbamazepine) 2
  • Rapid dexamethasone absorption/malabsorption 1
  • Increased cortisol-binding globulin levels 1

• False negative results (suppression despite Cushing's) can occur with:

  • Medications inhibiting dexamethasone metabolism (fluoxetine, cimetidine) 2
  • Decreased cortisol-binding globulin levels 1

Clinical Significance

• The substantial decrease in cortisol levels with elevated dexamethasone demonstrates appropriate negative feedback of the HPA axis 2
• This result is inconsistent with the pattern seen in Cushing's syndrome, where cortisol would remain elevated despite dexamethasone administration 1, 2
• For most subjects with plasma dexamethasone >5 nmol/L, there is no association between dexamethasone and cortisol levels, suggesting adequate suppression 3

Next Steps

• If clinical suspicion for Cushing's syndrome remains despite these results:
  • Consider other screening tests such as late-night salivary cortisol or 24-hour urinary free cortisol 1
  • Evaluate for potential causes of false results as mentioned above 1, 2
  • Consider primary adrenal insufficiency if cortisol levels are consistently low even without dexamethasone 4