From the Guidelines
In the context of overnight dexamethasone testing, a serum cortisol level of less than 1.8 μg/dL (50 nmol/L) the morning after taking 1 mg of dexamethasone is considered a normal response, indicating proper functioning of the hypothalamic-pituitary-adrenal axis. This threshold is based on the most recent guideline update from 2021, as outlined in the consensus on diagnosis and management of Cushing's disease published in The Lancet Diabetes and Endocrinology 1. The overnight dexamethasone suppression test is a crucial diagnostic tool for assessing cortisol regulation, with values above the 1.8 μg/dL threshold suggesting abnormal cortisol regulation and potentially indicating conditions like Cushing's syndrome.
Key points to consider in interpreting the results of the overnight dexamethasone suppression test include:
- A serum cortisol level of less than 1.8 μg/dL (50 nmol/L) is considered a normal response, strongly predicting the absence of Cushing's syndrome (CS) 1.
- Higher cutoff points, such as 5 μg/dL (138 nmol/L), reduce the sensitivity of the test 1.
- False-positive results can occur due to factors such as rapid absorption or malabsorption of dexamethasone, concomitant treatment with CYP3A4 inducers, and increased corticosteroid binding globulin (CBG) levels 1.
- Measuring dexamethasone concomitantly with cortisol and using laboratory-specific ranges can help reduce the risk of false-positive results 1.
- False-negative results are less common but can be caused by inhibition of dexamethasone metabolism by certain medications or decreased CBG and albumin levels 1.
In clinical practice, it is essential to consider these factors and interpret the results of the overnight dexamethasone suppression test in the context of the individual patient's clinical presentation and medical history, as outlined in the guideline update 1.
From the Research
Expected Serum Cortisol Results for Overnight Dexamethasone Testing
- The normal value after dexamethasone suppression is less than 2 micrograms/dL, rather than less than 5 micrograms/dL as has generally been accepted 2.
- Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 microg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %) 3.
- A cut-off of > 2 microg/dL gave similar sensitivity, and even with a stringent cut-off point of > 1.8 microg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %) 3.
- Cortisol after 1-mg DST confirmed high sensitivity (100% at 50 nmol/L cut-off) and moderate-low specificity (63%, increased to 91% at 138 nmol/L) to diagnose Cushing's syndrome in the whole cohort of patients 4.
- The use of 5 micrograms/dL as the normal value may lead to an unnecessary delay in diagnosis, as some individuals with Cushing's syndrome partially suppress their cortisol levels to less than 5 but more than 2 micrograms/dL during the test procedure 2.
Dexamethasone and Cortisol Concentrations
- Plasma dexamethasone was associated with plasma cortisol (P<0.001), and the regression line suggested a strong negative association related to dexamethasone levels <5 nmol/l 5.
- However, among the 94% of subjects with plasma dexamethasone >5.0 nmol/l, there was no association between dexamethasone and cortisol levels (P=0.55) 5.
- Dexamethasone measurements may identify subjects with inadequately low plasma dexamethasone and may therefore be of value when retesting subjects with possibly false-positive DST results 5.