https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)61375-1.pdf

Cushing's syndrome

Free Cortisol Levels after Awakening: A Reliable Biological Marker for the Assessment of Adrenocortical Activity

This review examines the diagnostic application of saliva for systemic diseases. As a diagnostic fluid, saliva offers distinctive advantages over serum because it can be collected non-invasively by individuals with modest training. Furthermore, saliva may provide a cost-effective approach for the screening of large populations. Gland-specific saliva can be used for diagnosis of pathology specific to one of the major salivary glands. Whole saliva, however, is most frequently used for diagnosis of systemic diseases, since it is readily collected and contains serum constituents. These constituents are derived from the local vasculature of the salivary glands and also reach the oral cavity via the flow of gingival fluid. Analysis of saliva may be useful for the diagnosis of hereditary disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in the assessment of therapeutic levels of drugs and the monitoring of illicit drug use.

https://journals.sagepub.com/doi/pdf/10.1177/154411130201300209

The Diagnostic Applications of Saliva— A Review:

Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement

Summary Objective The aim of this study was to determine whether salivary cortisol measured by a simple enzyme immunoassay (EIA) could be used as a surrogate for serum total cortisol in response to rapid changes and across a wide range of concentrations. Design Comparisons of matched salivary and serum samples in response to dynamic hypothalamic‐pituitary‐adrenal (HPA) axis testing. Subjects Healthy women ( n = 10; three taking oral oestrogens) and men ( n = 2), aged 23‐ 65 years, were recruited from the community. Measurements Paired saliva and serum samples were obtained during three protocols: 10 min of exercise at 90% of maximal heart rate ( n = 8), intravenous administration of corticotrophin-releasing hormone (CRH; n = 4), and dexamethasone suppression ( n = 7). Cortisol was measured in saliva using a commercial high-sensitivity EIA and total cortisol was measured in serum with a commercial radioimmunoassay (RIA). Results The time course of the salivary cortisol response to both the exercise and CRH tests paralleled that of total serum cortisol. Salivary cortisol demonstrated a significantly greater relative increase in response to the exercise and CRH stimuli (697 ± 826% vs. 209 ± 150%, P = 0·04 saliva vs. serum). A disproportionately larger increase in free cortisol, compared with total, would be expected when the binding capacity of cortisol-binding globulin (CBG) is exceeded. In response to dexamethasone suppression, relative decreases in cortisol were not significantly different between the two media ( − 47 ± 56% vs. − 84 ± 8%, P = 0·13 saliva vs. serum). Although a significant linear correlation was found for all paired salivary and serum total cortisol samples ( n = 183 pairs, r = 0·60, P < 0·001), an exponential model provided a better fit ( r = 0·81, P < 0·001). The linear correlations were strengthened when data from subjects on oral oestrogens ( n = 52 pairs, r = 0·75, P < 0·001) were separated from those not taking oestrogens ( n = 131 pairs, r = 0·67, P < 0·001). Conclusions Salivary cortisol measured with a simple EIA can be used in place of serum total cortisol in physiological research protocols. Evidence that salivary measures represent the biologically active, free fraction of cortisol includes: (1) the greater relative increase in salivary cortisol in response to tests that raise the absolute cortisol concentration above the saturation point of CBG; (2) the strong exponential relationship between cortisol assessed in the two media; and (3) the improved linear correlations when subjects known to have increased CBG were analysed separately. Thus, an advantage of measuring salivary cortisol rather than total serum cortisol is that it eliminates the need to account for within-subject changes or between-subject differences in CBG.

https://www.hormonebalance.org/images/documents/Salivary%20not%20serum%20cortisol%20CE%2005.pdf

Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic–pituitary–adrenal axis activity

SUMMARY
Cortisol concentrations were determined in matched samples of plasma and saliva from patients and healthy volunteers throughout the course of standard tests of pituitary and adrenal reserve. During insulin tolerance tests the percentage incremental changes in cortisol concentrations in saliva were strictly comparable with those in plasma and showed less inter-subject variance. The clinical decision taken with regard to the integrity of the pituitary-adrenal axis was the same whether plasma or salivary cortisol was measured. In the short tetracosactrin test changes in salivary cortisol reflected those in plasma and patients with loss of adrenal responsiveness would have been diagnosed as such using either measurement. In normal subjects, the circadian rhythm in salivary cortisol concentrations exactly paralleled that in plasma. Absence of the circadian rhythm in cases of hypercortisolism was seen as well in saliva as in plasma. Assays for salivary cortisol therefore provide information which is as clinically useful as that of plasma determinations. Since salivary cortisol concentrations were shown to reflect the free, biologically active fraction in plasma, salivary assay may, in selected cases, provide results of greater diagnostic significance than plasma total concentrations.

Salivary cortisol assays for assessing pituitary‐adrenal reserve

Total plasma cortisol measurements may be misleading when there are variations in the plasma cortisol-binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol-binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic-pituitary-adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary-dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half-life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary-dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Salivary cortisol levels in true and apparent hypercortisolism

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Salivary cortisol assays for assessing pituitary‐adrenal reserve

Salivary cortisol levels in true and apparent hypercortisolism