Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test

Eur J Endocrinol. 2017 Jun;176(6):705-713. doi: 10.1530/EJE-17-0078. Epub 2017 Mar 15.

Abstract

Objectives: The overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum.

Design and methods: Prospective study of DST was carried out in patients with suspected Cushing's syndrome (CS) (n = 49), incidentaloma (n = 152) and healthy controls (n = 101). Cortisol, cortisone and DXM were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results: Three hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST (n = 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort (n = 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol.

Conclusions: Simultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS.

MeSH terms

  • Adenoma / diagnosis*
  • Adenoma / metabolism
  • Adolescent
  • Adrenal Gland Neoplasms / diagnosis*
  • Adrenal Gland Neoplasms / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Chromatography, Liquid
  • Cortisone / metabolism*
  • Cushing Syndrome / diagnosis*
  • Cushing Syndrome / metabolism
  • Dexamethasone / metabolism*
  • Female
  • Humans
  • Hydrocortisone / metabolism*
  • Incidental Findings
  • Male
  • Middle Aged
  • Prospective Studies
  • Saliva / chemistry
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • Dexamethasone
  • Cortisone
  • Hydrocortisone