Endocrine Connections (Apr 2023)

Expanding the use of salivary cortisol as a non-invasive outpatient test in the dynamic evaluation of suspected adrenal insufficiency

  • Sarah Ying Tse Tan,
  • Hong Chang Tan,
  • Ling Zhu,
  • Lih Ming Loh,
  • Dawn Shao Ting Lim,
  • Du Soon Swee,
  • Yoke Ling Chan,
  • Huee Boon Lim,
  • Shiau Lee Ling,
  • En Jun Ou,
  • Wynn Ee Teo,
  • Xiao Ping Zhang,
  • Hui Fen Goh,
  • Peng Chin Kek

DOI
https://doi.org/10.1530/EC-23-0004
Journal volume & issue
Vol. 12, no. 4
pp. 1 – 9

Abstract

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Background: Adrenal insufficiency (AI) is potentially life-threatening, and accurate diagnosis is crucial. The first-line diagnostic test, the adreno corticotrophic hormone (ACTH) stimulation test, measures serum total cortisol. However , this is affected in states of altered albumin or cortisol-binding globulin levels, limitin g reliability. Salivary cortisol reflects free bioactive cortisol levels and is a promising alter native. However, few studies are available, and heterogenous methodologies limit applicability. Methods: This study prospectively recruited 42 outpatients undergoing ev aluation for AI, excluding participants with altered cortisol-binding states. Serum (immunoassay) and salivary (liquid chromatography tandem mass spectrometry) c ortisol levels were sampled at baseline, 30 min, and 60 min following 250 μg synact hen administration. AI was defined as a peak serum cortisol level <500 nmol/L in acc ordance with guidelines. Results: The study recruited 21 (50%) participants with AI and 21 withou t AI. There were no significant differences in baseline characteristics, blood pre ssure, or sodium levels between groups. Following synacthen stimulation, serum and sali vary cortisol levels showed good correlation at all timepoints (R2 = 0.74, P < 0.001), at peak levels (R2 = 0.72, P < 0.001), and at 60 min (R2 = 0.72, P < 0.001). A salivary cortisol cut-off of 16.0 nmol/L had a sensitivity of 90.5% and a specificity of 76.2% for the di agnosis of AI. Conclusion: This study demonstrates a good correlation between serum and sa livary cortisol levels during the 250 μg synacthen test. A peak saliva ry cortisol cut-off of 16.0 nmol/L can be used for the diagnosis of AI. It is a less i nvasive alternative to evaluate patients with suspected AI. Its potential utility in the diagno sis of AI in patients with altered cortisol-binding states should be further studied.

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