From the Guidelines
The cortisol level of 6.4 after the overnight dexamethasone suppression test indicates an abnormal result, suggesting possible Cushing's syndrome or autonomous cortisol secretion. Normal suppression should result in a morning cortisol level below 1.8 μg/dL (50 nmol/L) [ 1 ]. This patient's elevated post-dexamethasone cortisol level indicates resistance to the suppressive effects of dexamethasone, which is characteristic of cortisol excess states.
Key Points to Consider
- The patient's cortisol level is above the threshold for normal suppression, suggesting autonomous cortisol production or resistance to feedback inhibition [ 1 ].
- Further evaluation is recommended, including additional testing such as 24-hour urinary free cortisol, late-night salivary cortisol, and possibly a longer low-dose dexamethasone suppression test (2 days) [ 1 ].
- Referral to an endocrinologist is appropriate for comprehensive evaluation and management.
- The overnight dexamethasone suppression test works by utilizing the negative feedback mechanism of cortisol on the hypothalamic-pituitary axis; in normal individuals, the exogenous dexamethasone suppresses ACTH production, leading to decreased cortisol secretion [ 1 ].
- Failure of suppression, as seen in this case, suggests autonomous cortisol production or resistance to feedback inhibition, which occurs in conditions like Cushing's syndrome, certain medications, severe stress, depression, alcoholism, or obesity [ 1 ].
Next Steps
- Additional testing to confirm the diagnosis and evaluate the severity of cortisol excess.
- Referral to an endocrinologist for comprehensive evaluation and management.
- Consideration of potential underlying causes of autonomous cortisol production, such as Cushing's syndrome or adrenal incidentaloma [ 1 ].
From the Research
Dexamethasone Suppression Testing
- The dexamethasone suppression test is used to evaluate patients with possible Cushing syndrome by assessing whether cortisol is suppressed the morning after an evening dexamethasone dose 2.
- A cortisol level of 6.4 after 1mg of dexamethasone taken 8 hours prior may indicate incomplete suppression of cortisol, suggesting potential Cushing syndrome or another form of hypercortisolism 3.
- However, the interpretation of dexamethasone suppression test results should be done in the context of clinical presentation and other diagnostic tests, such as 24-hour urinary free cortisol or late-night salivary cortisol tests 2.
Diagnostic Criteria
- Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology 2.
- The estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually 2.
- Diagnostic evaluation of Cushing syndrome involves ruling out exogenous steroid use, followed by screening for elevated cortisol using various tests, including the dexamethasone suppression test 2, 3.
Treatment Options
- First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor 2, 3.
- Medical therapy, including adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers, may be used in preparation for surgery, when surgery is unsuccessful, or when the effects of radiotherapy are being awaited 3, 4, 5, 6.
- Adrenally directed medical therapies, such as ketoconazole, metyrapone, osilodrostat, mitotane, and etomidate, can be effective in reducing hypercortisolism, but require careful dose titration and patient monitoring to avoid hypoadrenalism 5, 6.