How to interpret elevated cortisol level after a 1 milligram (mg) dexamethasone (generic name) suppression test, with a result of 3.4 micrograms per deciliter (ug/dL) at 9 hours (9H)?

From the Guidelines

The high cortisol level of 3.4 μg/dL after a 1 mg dexamethasone suppression test indicates a failure to suppress cortisol production, suggesting possible Cushing's syndrome. This test works by giving 1 mg of dexamethasone at night, which should suppress cortisol production by morning in healthy individuals to below 1.8 μg/dL, as stated in the consensus guideline update 1. Since your level is 3.4 μg/dL, this is abnormal and requires further evaluation. You should consult with an endocrinologist for additional testing to determine the cause, which could be a pituitary tumor (Cushing's disease), adrenal tumor, or ectopic ACTH production.

Some key points to consider in the interpretation of this test result include:

• False positive results may be seen with rapid absorption/malabsorption of dexamethasone due to increased gut transit time, chronic diarrhea, or celiac disease; concomitant treatment with CYP3A4 inducers (e.g., phenobarbital, carbamazepine, St. John’s wort); and increased corticosteroid binding globulin (CBG) levels from oral estrogens, pregnancy, or chronic active hepatitis, which may increase total cortisol levels 1.
• Measuring dexamethasone concomitantly with cortisol, using laboratory-specific ranges of expected values, can reduce the risk for false-positive results 1.
• Further tests may include a 24-hour urinary free cortisol test, late-night salivary cortisol, or higher-dose dexamethasone suppression tests.
• It is essential not to stop any medications without medical advice, as some medications like oral contraceptives or certain antidepressants can affect test results 1.
• Cushing's syndrome can cause serious health problems, including high blood pressure, diabetes, and bone loss, so proper diagnosis and treatment are crucial. The management of Cushing's syndrome may involve surgical intervention, such as adrenalectomy, which should be considered on a case-by-case basis, taking into account the size and characteristics of the adrenal mass, as well as the patient's overall health and preferences 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Interpretation of High Cortisol Levels after Dexamethasone Suppression Test

• The given result of 3.4 ug/dL for cortisol levels after a 1 mg dexamethasone suppression test is higher than the normal value of less than 2 micrograms/dL, as indicated by 2.
• This suggests that the cortisol levels did not suppress as expected after the administration of dexamethasone, which could be indicative of Cushing's syndrome or other adrenal disorders.
• According to 3, the high-dose dexamethasone suppression test using urine free cortisol as an end point can help differentiate between pituitary and non-pituitary disease, but the degree of suppression required for diagnosis may vary.
• The study 4 found that post-overnight 1-mg dexamethasone suppression salivary cortisone levels can be useful in the investigation of hypercortisolism, with a cut-off of 7.45 nmol/L having a sensitivity of 85.7% and a specificity of 94.9%.
• Another study 5 discussed the accuracy and pitfalls of the overnight 1 mg dexamethasone suppression test and 24 h urine free cortisol when screening for Cushing's syndrome, highlighting the importance of considering the distinctive features of each test.
• A comparison of serum cortisol and 24 hour urine free cortisol in combined dexamethasone suppression test, as reported in 6, found that serum cortisol <50 nmol/L had a higher sensitivity than 24 h UFC <32 nmol in determining the diagnosis of Cushing's syndrome.

Possible Implications

• The elevated cortisol level after dexamethasone suppression may indicate the need for further evaluation and testing to determine the underlying cause of the abnormal result.
• The results of the dexamethasone suppression test should be considered in conjunction with other clinical and laboratory findings to establish a diagnosis.
• The choice of test and interpretation of results may depend on the specific clinical context and the presence of other symptoms or signs of adrenal disorders, as discussed in 3 and 6.