The Utility of Salivary 11-Dehydrodexamethasone as a Marker of Dexamethasone Absorption.

Abstract

The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the investigation of hypercortisolism and adrenal incidentalomas. Measurement of cortisol and dexamethasone (DXM) has been shown to improve diagnostic sensitivity of the ONDST. Recent work has shown that salivary cortisone collection can be undertaken at home replacing serum sampling, but previous studies have found poor performance of salivary DXM after the ONSDT. Herein we introduce the concept of measuring 11-dehydrodexamethasone (11-DHD): a DXM metabolite produced in the salivary duct by metabolism of 11β-hydroxysteroid dehydrogenase type 2, as a surrogate marker for DXM absorption. Paired 0900h serum and saliva samples (n=90) were collected post-ONDST. Independent liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were used to measure serum cortisol and DXM. A novel LC-MS/MS assay was developed to measure salivary cortisol, cortisone, DXM and 11-DHD. Results were compared and correlations were assessed using Pearson's correlation coefficient. Serum and salivary DXM results exhibited a poor correlation (R-squared = 0.135). Salivary DXM and 11-DHD also correlated poorly (R-squared = 0.163). Serum DXM and salivary 11-DHD yielded a positive correlation with an R-squared of 0.75. The positive relationship between serum DXM and salivary 11-DHD is novel. At higher concentrations of DXM, the correlation becomes somewhat curvilinear and more variable. A similar relationship is seen between salivary cortisol and cortisone. The development of a salivary 11-DHD LC-MS/MS assay has the potential to improve the current patient pathway. Patients could administer the drug and collect a 0900h-saliva sample at their convenience, prior to posting for analysis.