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

Abstract

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.

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“…This finding is supported by previous studies showing a strongly positive correlation between salivary and serum cortisol levels measured by other methods 9,10 . Salivary cortisol reflects the biologically active free form of cortisol, thereby providing a more reliable measure than serum cortisol which is an inactive bound form 2 .…”

The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma

“…Salivary cortisol offers several advantages: it reflects the unbound fraction of circulating cortisol, it is not influenced by saliva flow rate, and it can be collected at home, eliminating the cost of hospitalization and the stress of hospital visit (26).…”

Salivary Cortisol Can Replace Free Serum Cortisol Measurements in Patients With Septic Shock

“…It has been postulated that salivary cortisol determination is more useful, especially after ACTH stimulation test, since it refl ects immediate changes in the unbound serum cortisol without being affected by the CBG or albumin concentration. 25 It has been suggested that critically ill patients with serum free cortisol concentration Յ 2 m g/dL are at risk for adrenal insuffi ciency. 18 Using this criterion, 53% (30 of 57) of the patients by free serum cortisol and 47% (18 of 38) by salivary cortisol concentration probably have adrenal insuffi ciency.…”

“…There is enough evidence to use free serum cortisol concentration, the biologically active hormone, instead of total serum cortisol CBG reaches saturation point the increase in serum free cortisol concentrations is refl ected in salivary cortisol in a few minutes ( , 5 min), even when total serum cortisol is still low. 25 Salivary cortisol determination omits the need to measure CBG to calculate the free cortisol level, and it is less altered by changes in protein concentration.…”