Endocrine Abstracts

Introduction: Low-dose dexamethasone suppression test is used to screen for excess cortisol production (Cushing’s syndrome). It is recommended to use cut-off for suppression of serum cortisol (SC) < 50 nmol/l after 1 mg dexamehason suppression test (DST). Plasma dexamethasone levels are affected by many factors resulting in lower test specificity. Simultaneous analysis of dexamethasone and cortisol levels can improve diagnostic accuracy of DST. We used cut-off level of plasma dexamethasone > 3 nmol/l, which was validated in our previous study. The aim of the study was to detect the rate of false positive results by measuring plasma dexamethasone level after DST.

Methods: The prospective study of DST was carried out in 116 patients (71 female, 45 male) and 100 healthy controls (60 female and 40 male). The patients’ cohort consisted of individuals with unilateral adrenal lesion (n=28), bilateral adrenal lesion (n=30), pituitary tumor (n=21) and clinically suspected Cushing’s syndrome (n=37). Serum cortisol was determined by chemiluminescence immunoassay (Atellica Siemens). Plasma cortisol and dexamethason were determined by liquid chromatography with tandem mass spectrometry (2D-LC-MS/MS).

Results: Sixty-nine patients (59%) achieved SC <50 nmol/l. All of them had sufficient plasma dexamethasone level (>3 nmol/l). Forty-seven patients (41%) had SC > 50 nmol/l, out of whom 44 achieved sufficient plasma dexamethasone levels while three did not. In this group of 47 patients further endocrinological examination ruled out hypercortisolism in 20 patients including 3 patients with insufficient dexamethasone levels and confirmed overt Cushing’s syndrome in 16 patients. Eleven patients were found to have possible autonomous cortisol secretion. In the group of 100 healthy controls, SC <50 nmol/l was reached in 91 cases (91%). Nine individuals had SC > 50 nmol/l, out of whom two patients had a level of plasma dexamethasone <3 nmol/l. In all nine individuals further endocrinological examination excluded hypercortisolism.

Conclusion: 2D-LC/MS/MS is considered to be the golden standard in the analysis of both steroid hormones and dexamethasone. Insufficient plasma dexamethasone levels were found in 2% of subjects and were therefore the cause of false positivity of 1 mg dexamethasone suppression test. Simultaneous measurement of plasma dexamethasone and cortisol improved the specificity of DST. The results confirm that DST can be falsely positive even in healthy individuals with sufficient levels of dexamethasone.