Diagnosing Cushing's Syndrome with Dexamethasone Suppression Test

Introduction to Diagnostic Tests

The Endocrine Society recommends the overnight 1-mg dexamethasone suppression test (DST) as a first-line screening test for Cushing's syndrome due to its high sensitivity and ability to effectively rule out the condition when negative 1
The overnight 1-mg DST has a normal response of cortisol <1.8 μg/dL (50 nmol/L), which strongly predicts absence of Cushing's syndrome 2

The American College of Endocrinology suggests that the 2-day Low-Dose DST (LDDST) has a sensitivity of 95% and specificity of 80% for diagnosing Cushing's syndrome, with a normal response of cortisol suppression below 50 nmol/L (1.8 μg/dL) 3
The overnight 1-mg DST is particularly useful for ruling out dysregulated cortisol production from adrenal incidentalomas 2

The European Society of Endocrinology recommends initial screening based on clinical suspicion, with low suspicion starting with late-night salivary cortisol (LNSC) and intermediate/high suspicion performing 2-3 screening tests (LNSC, 24h UFC, overnight DST) 1, 4
Normal screening results indicate Cushing's syndrome is unlikely, while abnormal results require repeat screening tests and persistently abnormal results proceed to ACTH measurement 1, 4

Measuring dexamethasone levels concomitantly with cortisol can reduce false-positive results, with a lower limit of normal dexamethasone concentration of 1.8 ng/mL (4.6 nmol/L) 2
Factors that may affect test interpretation include false positives due to rapid dexamethasone absorption/malabsorption, CYP3A4 inducers, and increased CBG levels, as well as false negatives due to inhibition of dexamethasone metabolism and decreased CBG levels 2

For adrenal incidentalomas, the Endocrine Society suggests that DST is particularly useful as a first-line test, with cortisol values >5 μg/dL generally identifying patients with dysregulated cortisol secretion from an incidentaloma 1, 2
In cases of suspected pseudo-Cushing's states, additional testing may be required as DST can yield false positives, and the combined LDDT-CRH (Dex-CRH) test may help distinguish between ACTH-dependent CS and pseudo-CS 4, 2

The Endocrine Society recommends that DST may be preferred for shift workers and patients with disrupted circadian rhythm due to uneven sleep schedules 5
The Endocrine Society suggests that DST may not be reliable in women treated with oral estrogen, and alternative tests such as the Dex-CRH test may be needed for suspected pseudo-Cushing states 5

Normal adrenal function is indicated by elevated dexamethasone with suppressed cortisol levels, consistent with appropriate response to the dexamethasone suppression test, as suggested by the Journal of Internal Medicine 6, 7
Primary adrenal insufficiency may be considered if cortisol levels are consistently low even without dexamethasone, according to the Journal of Internal Medicine 6, 7