Salivary cortisol response to ACTH stimulation is a reliable alternative to serum cortisol in evaluating hypoadrenalism

El-Farhan, Nadia, Tennant, Sarah, Rees, Seren E., Evans, Carol and Rees, D. Aled ORCID: https://orcid.org/0000-0002-1165-9092 2024. Salivary cortisol response to ACTH stimulation is a reliable alternative to serum cortisol in evaluating hypoadrenalism. The Journal of Clinical Endocrinology & Metabolism 109 (2) , e579-e588. 10.1210/clinem/dgad576

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Abstract

Context The serum total cortisol response to the ACTH stimulation test is widely used to assess adrenocortical function but is affected by changes in cortisol-binding globulin (CBG) concentration. Salivary cortisol reflects free cortisol concentrations and may offer a reliable alternative. Objectives 1: To establish the salivary cortisol response to ACTH stimulation in healthy volunteers and patients with altered CBG concentrations. 2. To evaluate the performance of a lower reference limit (LRL) determined in healthy volunteers in patients with suspected hypoadrenalism (SH-patients). Design A 250 µg-ACTH stimulation test was undertaken in 139 healthy volunteers, 24 women taking an estradiol-containing oral contraceptive pill (OCP-females), 10 patients with low serum protein concentration (LP-patients) and 30 SH-patients. Salivary cortisol was measured by liquid chromatography-tandem mass spectrometry. Mean and LRL of the 30-minute salivary cortisol response (mean - 1.96 standard deviation) were derived from log-transformed concentrations. The LRL was applied as a diagnostic cut-off in SH-patients, with comparison to the serum response. Results Mean CBG concentrations [range] were 58 [42-81] mg/L, 64 [43-95] mg/L, 41 [28-60] mg/L and 116 [84-159] mg/L in males, females, LP-patients and OCP-females, respectively. The mean 30-minute salivary cortisol concentration was 19.3 [2.5th-97.5th percentile 10.3-36.2] nmol/l in healthy volunteers. Corresponding values were not different in OCP-females (19.7 [9.5-41.2] nmol/l; p = 0.59) or LP-patients (19.0 [7.7-46.9] nmol/l; p = 0.97). Overall diagnostic agreement between salivary and serum responses in SH-patients was 79%. Conclusions Salivary cortisol response to ACTH stimulation offers a reliable alternative to serum and may be especially useful in conditions of altered CBG concentration.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Publisher:	Oxford University Press
ISSN:	0021-972X
Date of First Compliant Deposit:	2 October 2023
Date of Acceptance:	27 September 2023
Last Modified:	27 Feb 2024 12:33
URI:	https://orca.cardiff.ac.uk/id/eprint/162866

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