SUMMARY Salivary cortisol concentration was found to be directly proportional to the serum unbound cortisol concentration both in normal men and women and in women with elevated cortisolbinding globulin (CBG). The correlation was excellent in dynamic tests of adrenal function (dexamethasone suppression, ACTH stimulation), in normals and patients with adrenal insufficiency, in tests of circadian variation and randomly collected samples. Women in the third trimester of normal pregnancy exhibited elevated salivary cortisol throughout the day. The relationship between salivary and serum total cortisol concentration was markedly non-linear with a more rapid increase in salivary concentration once the serum CBG was saturated. The rate of equilibrium of cortisol between blood and saliva was very fast, being much less than 5 minutes. These data, combined with a simple, stress-free, non-invasive collection procedure, lead us to suggest that salivary cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum cortisol. Materials and methods SUBJECTSCircadian variation The circadian rhythm of salivary cortisol was examined in seven female and seven male healthy adults (age range 24-32 years). Each subject collected a saliva sample every hour for one day throughout their normal waking hours. On another day the same groups provided matched serum and saliva samples at 0900 and 1700. The circadian rhythm of salivary cortisol in the third trimester of normal pregnancy was examined in 13 sets of samples from 10 women (age range 22-35 years) with uncomplicated pregnancies who delivered healthy single babies at 38-42 weeks' gestation. dexamethasone suppression, adrenocorticotrophin (ACTH) stimulation, and circadian variation; (3) examined the circadian variation of salivary cortisol in women in the third trimester of normal pregnancy; and (4) examined the rate of appearance of cortisol in saliva.
Assay of hormones in saliva would be more convenient than assay in blood, but there is no information on the route by which hormones enter saliva, information that would provide insight into the clinical value of such assays. We have examined the mode of entry of various hormones into saliva. The results suggest that unconjugated steroids enter saliva by diffusing through the cells of the salivary glands and that their concentration in saliva does not depend on the rate of saliva production. Conjugated steroids enter saliva via "ultrafiltration" through the tight junctions between the acinar cells, and their concentration in saliva is highly flow-rate dependent. Thyroxin and choriogonadotropin enter saliva via the ultrafiltration route or by contamination of the saliva by plasma or gingival fluid. We conclude that the salivary concentration of unconjugated steroids may usefully reflect the concentration of free (nonprotein-bound) steroids in plasma. Conversely, the concentration of conjugated steroids, thyroxin, and protein hormones such as choriogonadotropin in saliva probably does not reflect their concentration in plasma in any clinically useful way.
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