Endocrinol Metab.  2020 Sep;35(3):628-635. 10.3803/EnM.2020.707.

Stimulated Salivary Cortisol as a Noninvasive Diagnostic Tool for Adrenal Insufficiency

• Kim YJ
• Kim JH
• Hong AR
• Park KS
• Kim SW
• Shin CS
• Kim SY

• KMID: 2508013
• DOI: http://doi.org/10.3803/EnM.2020.707

Abstract

Background
Salivary cortisol is routinely used as a diagnostic test for Cushing syndrome. The diagnostic use of salivary cortisol for adrenal insufficiency (AI), however, is less established. We aimed to investigate the utility of morning basal and adrenocorticotropic hormone-stimulated salivary cortisol in diagnosing AI in Korean adults.
Methods
We prospectively included 120 subjects (female, n=70) from Seoul National University Hospital. AI was defined as a stimulated serum cortisol level of <496.8 nmol/L during the short Synacthen test (SST). Serum and saliva samples were drawn between 8:00 AM and 10:00 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit.
Results
Thirty-four patients were diagnosed with AI according to the SST results. Age, sex, body mass index, serum albumin levels, and serum creatinine levels did not significantly differ between the normal and AI groups. Basal and stimulated salivary cortisol levels were positively correlated with basal (r=0.538) and stimulated serum cortisol levels (r=0.750), respectively (all P<0.001). Receiver operating characteristic curve analysis yielded a cutoff level of morning basal salivary cortisol of 3.2 nmol/L (sensitivity, 84.9%; specificity, 73.5%; area under the curve [AUC]=0.822). The optimal cutoff value of stimulated salivary cortisol was 13.2 nmol/L (sensitivity, 90.7%; specificity, 94.1%; AUC=0.959). Subjects with a stimulated salivary cortisol level above 13.2 nmol/L but a stimulated serum cortisol level below 496.8 nmol/L (n=2) had lower serum albumin levels than those showing a concordant response.
Conclusion
The diagnostic performance of stimulated salivary cortisol measurements after the SST was comparable to serum cortisol measurements for diagnosing AI.

Keyword

Saliva; Adrenal insufficiency; Hydrocortisone

Figure

• 

  Fig. 1 Flow diagram of the study design. CBG, corticosteroid-binding globulin.

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  Fig. 2 Median cortisol values in (A) serum and (B) saliva at 30 and 60 minutes after intravenous administration of 250 μg of synthetic adrenocorticotropic hormone (ACTH1–24; Synacthen). The median levels of serum and salivary cortisol at 60 minutes were significantly lower in the adrenal insufficiency (AI) group than in the normal group (351.9 nmol/L vs. 836.3 nmol/L for serum; 5.4 nmol/L vs. 23.4 nmol/L for saliva, respectively).

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  Fig. 3 Scatter plots between (A) basal or (B) stimulated serum and salivary cortisol levels. There were significant positive associations between serum and salivary cortisol levels at basal and peak time (r=0.750 and r=0.538, respectively; all P<0.001).

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  Fig. 4 Receiver operating characteristic (ROC) curve of (A) basal and (B) stimulated salivary cortisol in the diagnosis of adrenal insufficiency (AI) in all subjects (n=120). The areas under the curve (AUCs) for basal and stimulated salivary cortisol were 0.822 and 0.959, respectively. The cutoff value of basal salivary cortisol for AI was 3.2 nmol/L (sensitivity, 84.9%; specificity, 73.5%). The optimal cutoff value of stimulated salivary cortisol for AI during the SST was 13.2 nmol/L (sensitivity, 90.7%; specificity, 94.1%). CI, confidence interval.

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