Should a dexamethasone (corticosteroid) suppression test be performed in a patient with a morning (AM) cortisol level at the high end of normal?

Should You Perform a Dexamethasone Suppression Test with AM Cortisol of 19 μg/dL?

No, a single morning cortisol of 19 μg/dL at the high end of normal does not, by itself, warrant a dexamethasone suppression test unless the patient has clinical features suggestive of Cushing's syndrome. 1, 2

Understanding the Clinical Context

A morning cortisol of 19 μg/dL (524 nmol/L) falls within the normal reference range of 5-23 μg/dL (138-635 nmol/L), with most healthy individuals having values between 10-20 μg/dL. 2 This value alone does not indicate hypercortisolism and effectively rules out adrenal insufficiency, as morning cortisol >14 μg/dL excludes this diagnosis. 2

When to Screen for Cushing's Syndrome

Screening should be reserved for patients with multiple, progressive clinical features of Cushing's syndrome, not based on a single cortisol value. 1, 3 Key clinical features that warrant screening include:

• Physical stigmata: Facial plethora, proximal muscle weakness, wide (>1 cm) purple striae, easy bruising, dorsocervical fat pad ("buffalo hump") 1, 3
• Metabolic complications: Hypertension, diabetes, osteoporosis in young patients 3
• Progressive symptoms: Weight gain with muscle wasting, mood disorders, hirsutism 3
• Adrenal incidentaloma: All patients with incidentally discovered adrenal masses must be screened for autonomous cortisol secretion 2

Critical Pitfalls: False Elevation of Morning Cortisol

Before pursuing any workup for hypercortisolism, you must exclude common causes of falsely elevated total cortisol levels: 2

• Oral contraceptives or estrogen therapy: These dramatically increase cortisol-binding globulin (CBG), raising total cortisol while free cortisol remains normal 1, 2
• Pregnancy: Increases CBG and elevates total cortisol measurements 1, 2
• Chronic active hepatitis: Can increase CBG production 1, 2
• Acute stress: Physical stressors (strenuous exercise within 24-48 hours) or psychological stress can transiently elevate cortisol 2
• Pseudo-Cushing's states: Severe obesity, psychiatric disorders, alcohol use disorder, and polycystic ovary syndrome can activate the HPA axis, causing mild cortisol elevation that mimics hypercortisolism 2

Appropriate Screening Tests When Indicated

If clinical suspicion for Cushing's syndrome is genuinely present, the overnight 1-mg dexamethasone suppression test is the preferred initial screening test, not a starting point based on a normal morning cortisol. 1, 2 The proper protocol involves:

• Administration: 1 mg dexamethasone given between 11 PM-midnight 1, 2
• Measurement: Serum cortisol at 8 AM the following morning 1, 2
• Interpretation: Cortisol <1.8 μg/dL (50 nmol/L) excludes hypercortisolism; cortisol >5 μg/dL (138 nmol/L) indicates overt Cushing's syndrome 1, 2
• Sensitivity and specificity: >90% sensitivity, with highest rates among screening tests 1

Alternative screening tests include: 1, 2

• Late-night salivary cortisol (LNSC): Collected at bedtime on 2-3 separate nights, with abnormal threshold >3.6 nmol/L; sensitivity 92-100%, specificity 93-100% 2
• 24-hour urinary free cortisol (UFC): At least 2-3 collections recommended due to 50% random variability; sensitivity >90% but lowest among screening tests 1, 2

Algorithmic Approach

Follow this decision pathway:

1. Assess clinical features: Does the patient have multiple, progressive signs/symptoms of Cushing's syndrome? 1, 3

   • If NO → No screening indicated; a morning cortisol of 19 μg/dL is normal
   • If YES → Proceed to step 2

2. Exclude false elevation: Is the patient on oral contraceptives, pregnant, or experiencing acute stress? 2

   • If YES → Address these factors first; consider free cortisol measurement if CBG elevation suspected
   • If NO → Proceed to step 3

3. Perform screening tests: Order overnight 1-mg dexamethasone suppression test as first-line 1, 2

   • Consider adding LNSC (2-3 samples) and/or 24-hour UFC (2-3 collections) for comprehensive evaluation 1, 2
   • Measuring dexamethasone levels concomitantly with cortisol can reduce false-positive results 1, 2

4. Interpret results: At least 2 abnormal screening tests are required before proceeding to further evaluation 2

Common Pitfalls to Avoid

• Do not screen based on a single normal cortisol value: A morning cortisol of 19 μg/dL does not indicate disease 2
• Do not ignore medication history: CYP3A4 inducers (phenobarbital, carbamazepine, St. John's wort) accelerate dexamethasone metabolism, causing false-positive DST results 1, 2
• Do not test shift workers with LNSC: Disrupted circadian rhythms invalidate this test; use DST instead 1, 2
• Do not pursue invasive testing without confirmed biochemical hypercortisolism: Inferior petrosal sinus sampling should never be used to diagnose hypercortisolism, only to localize the source after biochemical confirmation 2