II. Indications: Cushing's Syndrome Screening
- Preferred test if adrenal tumor suspected or Night Shift Worker (altered circadian rhythm)
- Among 3 first line options for Cushing's Syndrome Screening
- See 24-hour Urinary Free Cortisol level
- See Late-Night Salivary Cortisol (LNSC)
III. Mechanism
- Test measures Adrenal Gland response to ACTH
- ACTH should decrease in response to Dexamethasone
- Decreased ACTH should result in decreased Cortisol
- Failure for Cortisol to suppress suggests 2 causes
- Pituitary GlandACTH over-produced or
- Adrenal GlandCortisol over-produced
IV. Protocol
- Step 1: Patient takes Dexamethasone 1 mg at 11 pm on day 1
- Step 2: Draw Serum Cortisol at 8-9 am on day 2
V. Interpretation (Based on 8 am Serum Cortisol on day 2)
- AM Serum Cortisol <5 mcg/dl (especially if <1.8 mcg/dl)
- Normal response (Suppresses)
- AM Serum Cortisol >5 mcg/dl
- Cushing's Disease
- Repeating with Dexamethasone 8 mg determines site
- Adrenal Gland source will not suppress
- Pituitary source will suppress
VI. Causes: False Positives
- Increased gastrointestinal transit (e.g. Diarrhea)
- Pseudo-Cushing's Syndrome
-
CYP3A4 Inducers (increase Dexamethasone metabolism)
- Neuropsychiatric drugs (Carbamazepine, Phenobarbital, Phenytoin,St. John's Wort)
- Rifampin
- Troglitazone
-
Corticosteroid Binding Globulin increased
- Pregnancy
- Estrogen
- Chronic hepatitis
VII. Causes: False Negatives
- Hepatic Impairment
- Renal Impairment (eGFR<60 ml/min)
- Hypoalbuminemia
- Corticosteroid Binding Globulin decreased
- CYP3A4 Inhibitors (decrease Dexamethasone metabolism)
VIII. Efficacy
- Some protocols recommend a 3 stage Dexamethasone test for higer Test Sensitivity
- Draw Serum Cortisol at 4 pm on day 1 before Dexamethasone
- Accuracy is also improved when Dexamethasone level is checked on day 2 (in addition to Cortisol)
- Low-Dose Dexamethasone Suppression Test
- Test Sensitivity: 85 to 90%
- Test Specificity: 95 to 99%
- Strong Negative Predictive Value