Saliva and bloodspot cortisol: novel sampling methods to assess hydrocortisone replacement therapy in hypoadrenal patients

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Abstract
In patients with hypoadrenalism, it is often difficult to assess the optimal dose of glucocorticoid replacement. Serial serum cortisol measurements for a cortisol day curve are sometimes used, but this has low acceptability for patients. In this study, we evaluate the reliability of saliva and capillary bloodspot cortisol as alternative methods in assessing cortisol profiles in hypoadrenal patients on hydrocortisone replacement. We first examined the correlations between serum cortisol, saliva and bloodspot cortisol in in-hospital patients not on glucocorticoid therapy. We then studied 18 hypoadrenal patients on hydrocortisone therapy and measured their serum, saliva and bloodspot cortisol concurrently at seven different time points in a single day. For in-hospital patients, a significant correlation exists between saliva and serum cortisol (R = 0.7121, P < 0.0001), but there is a stronger correlation between bloodspot and serum cortisol (R = 0.9494, P < 0.0001). The correlations were weaker in hypoadrenal patients on hydrocortisone (saliva and serum cortisol: R = 0.6262, P < 0.001; bloodspot and serum cortisol: R = 0.7871, P < 0.001). When we evaluated each measurement with respect to an arbitrary target range, there was a greater degree of agreement between serum and capillary bloodspot cortisol (85% agreement) than between serum and saliva cortisol (65% agreement) (P < 0.001). Bloodspot samplings provide a simple and convenient way for ambulant hypoadrenal patients on hydrocortisone replacement therapy to assess cortisol levels at multiple times in a single day. This may be useful in determining the optimal glucocorticoid dose for hypoadrenal patients.