Endocrine Abstracts

Background: 1-mg overnight dexamethasone-suppression test (DST) is commonly used to screen for hypercortisolism. Sensitivity is high (95%), but specificity is low (80%), leading to false positive results. Identifying individuals with abnormal dexamethasone absorption or metabolism could enhance diagnostic accuracy.

Aim: Use serum dexamethasone (s-DXT) to increase diagnostic accuracy of DST.

Methods: Prospective study of DST for clinical suspicion of Cushing’s syndrome (CS) (n=49), incidentaloma (n=152), and healthy controls (n=101). S-cortisol and s-DXT were assayed by liquid chromatography tandem mass spectrometry (LCMSMS). DST results were correlated to the final diagnosis based on current clinical guidelines.

Results: 83/302 did not suppress s-cortisol (<50 nmol/l). Of these 11 had overt CS, and 27 subclinical CS (16% of the incidentalomas). A s-DXT cut-off level at 3.3 nmol/l was chosen based on the 2.5% quantile of DXT in those suppressing s-cortisol <50 nmol/l. Applying this cut-off, 10/302 (3.3%) DSTs were false positive with both inadequate s-DXT-levels and elevated s-cortisol. Of these, three were misdiagnosed as subclinical-CS. 12% of the positive DSTs could be explained by low levels of s- DXT. Among non-CS samples, s-cortisol values were higher in the incidentaloma-group (median 42.5 nmol/l, range 13–576) than in those with clinically suspected but not confirmed CS (22.7 nmol/l, 9.9–289) (P<0.01) and healthy controls (22.2 nmol/l, 8.4–102) (P<0.01). These findings were similar after eliminating patients with the lowest levels of DXT and estrogen users (n=16). Repeating DST in 30 healthy individuals shows excellent reproducibility of the test (interclass coefficient, ICC=0,936).

Conclusions: Abnormal absorption or metabolism of dexamethasone is a common reason for false positive 1-mg DSTs. Simultaneous measurement of s-DXT increases the accuracy of the test, and reduces the risk of falsely diagnosing subclinical CS. A minimum s-DXT level of 3.3 nmol/l is needed to suppress S- cortisol <50 nmol/l.