80
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7.5
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1
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80
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12
mcg/dL
0
1.8
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7.5
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0
The Cortisol Suppression Test Calculator evaluates the results of the dexamethasone suppression test (DST), the cornerstone diagnostic tool for Cushing syndrome. This calculator interprets results from all four standard DST protocols: the overnight 1-mg DST, the low-dose 2-day DST, the overnight high-dose (8-mg) DST, and the high-dose 2-day DST, providing suppression percentages and clinical interpretation.
Cushing syndrome results from chronic excess cortisol exposure, affecting approximately 2-3 per million people annually. It can be ACTH-dependent (~80% of cases, from pituitary adenomas causing Cushing disease or ectopic ACTH-producing tumors) or ACTH-independent (~20%, from adrenal adenomas, carcinomas, or bilateral hyperplasia). Early diagnosis is critical because untreated Cushing syndrome causes hypertension, diabetes, osteoporosis, infections, thromboembolism, and significantly increased mortality.
The DST works on the principle of negative feedback. Dexamethasone, a synthetic glucocorticoid approximately 30 times more potent than cortisol, normally suppresses ACTH secretion from the pituitary, which in turn reduces cortisol production by the adrenals. In Cushing syndrome, this feedback loop is disrupted — autonomous cortisol production continues despite exogenous glucocorticoid administration.
The overnight 1-mg DST is the most commonly used screening test. The patient takes 1 mg dexamethasone at 11 PM, and serum cortisol is measured at 8 AM the next morning. Normal suppression is defined as cortisol <1.8 mcg/dL (50 nmol/L). This test has a sensitivity of ~95-98% but specificity of only 70-80%, meaning false positives are common. The low-dose 2-day DST (0.5 mg every 6 hours for 48 hours) is slightly more specific.
High-dose DSTs are used after Cushing syndrome is confirmed to differentiate the cause. Pituitary adenomas (Cushing disease) typically retain some ACTH responsiveness and show >50% cortisol suppression with high-dose dexamethasone, while ectopic ACTH tumors and adrenal tumors generally do not suppress. This distinction is crucial for directing further workup (MRI pituitary vs CT chest/abdomen) and surgical planning.
The calculator applies the following logic:
Cortisol Suppression % = (Baseline - Post-Dex) / Baseline x 100
Low-Dose Tests (1-mg overnight, 2-day low-dose): Post-dexamethasone cortisol <1.8 mcg/dL = Adequate suppression (Cushing unlikely). ≥1.8 mcg/dL = Inadequate suppression (Cushing possible).
High-Dose Tests (8-mg overnight, 2-day high-dose): >50% suppression from baseline suggests pituitary Cushing disease. <50% suppression suggests ectopic ACTH or adrenal tumor.
Interpretation codes: 1 = Normal suppression (Cushing unlikely); 2 = Inadequate suppression (evaluate for Cushing); 3 = Suppresses with high dose (likely pituitary); 4 = No suppression on high dose (likely ectopic/adrenal).
Interpretation 1 (Normal Suppression): Post-dex cortisol <1.8 mcg/dL on low-dose test. Cushing syndrome is unlikely, though false negatives occur in ~2-5% of cases. If clinical suspicion remains high, proceed with 24-hour urinary free cortisol or late-night salivary cortisol. Interpretation 2 (Inadequate Suppression): Suggests possible Cushing syndrome. Confirm with additional tests (UFC, midnight salivary cortisol, CRH stimulation). Note false positives with depression, alcohol use, obesity, sleep apnea, and high-estrogen states. Interpretation 3 (High-Dose Suppression): Likely pituitary Cushing disease. Obtain pituitary MRI and consider IPSS. Interpretation 4 (No High-Dose Suppression): Suggests ectopic ACTH or adrenal source. Check ACTH; obtain CT chest/abdomen.
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Results
Post-dex cortisol 1.2 is below 1.8 threshold. 92% suppression. Normal — Cushing syndrome is effectively excluded.
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Results
64% suppression on high-dose DST with elevated ACTH (65 pg/mL) suggests pituitary Cushing disease. MRI pituitary recommended.
The DST measures the pituitary-adrenal axis response to an exogenous glucocorticoid (dexamethasone). In healthy individuals, dexamethasone suppresses ACTH and cortisol production. In Cushing syndrome, cortisol fails to suppress adequately because of autonomous production from a pituitary, adrenal, or ectopic source.
The 1.8 mcg/dL (50 nmol/L) cutoff for the low-dose DST was chosen to maximize sensitivity (~95-98%) at the expense of specificity (~70-80%). A lower cutoff of 1.4 mcg/dL increases sensitivity to ~98% but reduces specificity further. This threshold effectively screens out Cushing syndrome when cortisol suppresses below it.
Common causes include: pseudo-Cushing states (major depression, alcoholism, severe obesity), medications that increase dexamethasone clearance (phenytoin, phenobarbital, rifampin, carbamazepine), oral estrogen use (increases cortisol-binding globulin), shift workers, acute illness, and non-compliance with dexamethasone intake.
Low-dose DST (1 mg or 2-day 0.5mg) screens for Cushing syndrome — does the patient have autonomous cortisol? High-dose DST (8 mg or 2-day 2mg) differentiates the cause — pituitary adenomas usually retain some ACTH sensitivity and suppress >50%, while ectopic and adrenal sources do not.
Cushing syndrome is any condition of chronic cortisol excess, regardless of cause. Cushing disease specifically refers to Cushing syndrome caused by an ACTH-secreting pituitary adenoma, which accounts for about 70% of ACTH-dependent cases. The distinction is important because Cushing disease is treated with pituitary surgery.
The 1-mg overnight DST has sensitivity of 95-98% and specificity of 70-80% for screening. False negative rate is low (2-5%), making it an excellent rule-out test. However, the false positive rate of 20-30% means abnormal results require confirmation with additional testing before diagnosis.
Borderline results require additional evaluation. Options include: 24-hour urinary free cortisol (2 collections), late-night salivary cortisol (2 measurements), the 2-day low-dose DST (more specific), or CRH stimulation test. At least two concordant abnormal tests are recommended before diagnosing Cushing syndrome.
Yes. CYP3A4 inducers (phenytoin, carbamazepine, rifampin) accelerate dexamethasone metabolism, leading to insufficient suppression and false positives. Oral estrogen increases cortisol-binding globulin, raising total cortisol measurements. Always document medications when interpreting DST results.
After confirming Cushing syndrome, ACTH level differentiates causes: ACTH >20 pg/mL suggests ACTH-dependent (pituitary or ectopic); ACTH <5 pg/mL suggests ACTH-independent (adrenal tumor or hyperplasia); 5-20 pg/mL is indeterminate and may need CRH stimulation. ACTH level guides further imaging and testing.
An abnormal low-dose DST triggers confirmatory testing (UFC, salivary cortisol). If confirmed, ACTH is measured to determine dependency. ACTH-dependent cases get high-dose DST, CRH stimulation, and pituitary MRI. ACTH-independent cases get adrenal CT/MRI. Inferior petrosal sinus sampling may be needed if pituitary MRI is negative.
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