What is the next step in managing a patient with a post-meridiem (PM) cortisol level suggestive of hypercortisolism?

Management of PM Cortisol of 11 mcg/dL

The next step is to perform a 1 mg dexamethasone suppression test (DST) to confirm autonomous cortisol secretion, as this PM cortisol level suggests possible hypercortisolism. 1

Initial Diagnostic Approach

A PM cortisol of 11 mcg/dL (approximately 303 nmol/L) is abnormally elevated and raises concern for hypercortisolism, as normal cortisol follows a circadian rhythm with a nadir occurring at night. 2

Recommended Screening Test

• The 1 mg DST is the preferred screening test for identifying autonomous cortisol secretion when clinically appropriate 1
• Administer 1 mg dexamethasone orally at 11 PM, then measure serum cortisol at 8 AM the following morning 1
• Interpretation of results: 1
  • <50 nmol/L (<1.8 mcg/dL): Excludes cortisol hypersecretion
  • 51-138 nmol/L (1.8-5.0 mcg/dL): Possible autonomous cortisol secretion
  • >138 nmol/L (>5.0 mcg/dL): Evidence of cortisol hypersecretion

Confirmatory Testing

If the DST is abnormal, proceed with additional confirmatory tests: 1

• 24-hour urinary free cortisol (UFC): Reflects integrated tissue exposure to free cortisol over 24 hours and provides assessment of endogenous hypercortisolism 2
• Late-night salivary cortisol: Measures the impaired circadian rhythm characteristic of Cushing's syndrome 2
• Plasma ACTH level: Should be measured to confirm ACTH independency in all patients considering intervention 1

Important Procedural Considerations

Potential Pitfalls to Avoid

• Drug interactions: Some medications can interfere with the DST, producing false-positive or false-negative results 2
• Ensure complete 24-hour urine collections with appropriate total volumes when measuring UFC 2
• Assay methodology matters: Antibody-based immunoassays can generate false-positive results due to cross-reactivity; liquid chromatography with tandem mass spectrometry is more specific 2
• Cyclic Cushing's syndrome can produce intermittent normal results, requiring repeated testing if clinical suspicion remains high 2

Clinical Context Assessment

Evaluate for signs and symptoms of hypercortisolism: 1

• Hypertension and fluid retention
• Weight gain, particularly central obesity
• Facial rounding and dorsocervical fat pad
• Purple striae and thin skin
• Glucose intolerance or diabetes
• Osteoporosis or bone fragility
• Mood disorders

Differential Diagnosis Workup

Once hypercortisolism is confirmed biochemically, determine the etiology: 1, 3

• Measure plasma ACTH to distinguish ACTH-dependent from ACTH-independent causes 1
• ACTH-independent (suppressed ACTH): Suggests primary adrenal pathology 3
  • Obtain adrenal imaging with CT or MRI 1
  • MRI accurately diagnoses adenoma in 83% of cases 3
• ACTH-dependent (normal or elevated ACTH): Suggests pituitary or ectopic source 4
  • Perform CRH stimulation test 4
  • Consider bilateral inferior petrosal sinus sampling if results are equivocal 4

Imaging Studies

For patients with confirmed autonomous cortisol secretion: 1

• Adrenal CT or MRI to characterize the adrenal mass
• Measure Hounsfield units (HU) on non-contrast CT: <10 HU suggests benign adenoma 1
• If HU ≥10, screen for pheochromocytoma with plasma or 24-hour urinary metanephrines before any intervention 1

Management Implications

The degree of cortisol suppression on DST correlates with cortisol-related complications and mortality. 5 Patients with confirmed autonomous cortisol secretion, even mild hypercortisolism, have increased risk of: 5

• Bone fragility and fractures
• Hypertension and cardiovascular events
• Diabetes mellitus
• Increased mortality

Surgical resection via adrenalectomy is the definitive treatment for unilateral cortisol-secreting adrenal adenomas and improves diabetes, hypertension, and reduces fracture risk. 5