Assessment of glucocorticoid therapy with salivary cortisol in secondary adrenal insufficiency

Abstract

Context: Appropriate glucocorticoid replacement therapy in adrenal insufficiency (AI) is crucial, given the risks of chronic under-or overtreatment, particularly in patients on multiple medications. Salivary sampling allows for non-invasive, stress-free cortisol measurement. Objective: To determine whether salivary cortisol measurement is helpful in assessing the adequacy of glucocorticoid therapy with cortisone acetate (CA) in patients with secondary AI. Design: A prospective cohort study at the Endocrinology Unit of Padua University Hospital. Methods: Six samples of salivary cortisol were collected from 28 patients with secondary AI on CA treatment and from 36 healthy volunteers at fixed times of the day, and used to calculate salivary cortisol levels at each time point and the area under the curve (AUC) across the different sampling times. Results: Salivary cortisol levels were lower in patients than in controls in the morning but no differences were found in the afternoon or at night before resting. Salivary cortisol levels were higher in patients immediately following CA administration. Ten patients showed an AUC above the 97.5th percentile of controls, without clinical signs of hypercortisolism, and salivary cortisol levels 90 min after each dose of CA predict the AUC. All patients had severe GH deficiency and there were no differences in salivary cortisol levels or AUC between patients treated or not with GH. Conclusions: Two salivary cortisol determinations, able to predict the daily AUC, may allow for assessing the adequacy of glucocorticoid replacement therapy in secondary AI and for identifying cases of overor undertreatment.

Performance of salivary cortisol in the diagnosis of Cushing's syndrome, adrenal incidentaloma, and adrenal insufficiency

“…In our series, we confirmed our previous results that MSC levels are lower in patients with established adrenal insufficiency than in healthy controls (19). We still use dynamic tests to discover adrenal insufficiency, but we suggest using periodic salivary cortisol evaluation to follow up patients (especially with pituitary disease) in order to perform the dynamic test at the correct time.…”

“…Healthy people show physiologically high levels of salivary cortisol when they wake up, and some authors have reported that low salivary cortisol levels may thus be a marker of adrenal insufficiency (2,6,19). None of these studies have looked for differences between primary and secondary adrenal insufficiency; in the latter, some residual HPA axis activity may be confounding.…”

Group 4: Replacement therapy for adrenal insufficiency

“…The assay of salivary cortisol 90 minutes after each dose was used to determine area under curve, which in comparison with control subject values could show over-dosage or under-dosage. It should be noted that patients with an area under curve higher than the control 97.5th percentile showed no obvious signs of overdose [50]. Conversely, Thomson et al showed great variability in salivary cortisol in a crossover study of 27 patients being treated with hydrocortisone (oral or IV), and did not show a good correlation between plasma and saliva levels, making it difficult to employ in current practice [51]; • cortisol in hair: hair growth (1 cm per month) and the correlation between cortisol level in the hair and exposure to glucocorticoids could allow detection of overdose or underdosage in patients with adrenal insufficiency.…”

Age and the metabolic syndrome affect salivary cortisol rhythm: data from a community sample

“…4 Briefly, subjects were asked to collect samples using the Salivette commercial device (Salivette ® , Sarstedt, Numbrecht, Germany). Absorbent synthetic swab rolls were to be soaked in the saliva for 2-3 min and then placed in syringes and kept in the participant's refrigerator.…”

“…3 Salivary cortisol sampling is now increasingly used to test for hypothalamic-pituitary-adrenal (HPA) axis disorders 3 and to titrate substitutive therapy in adrenal insufficiency. 4 The noninvasive and readily repeatable nature of the assay makes salivary cortisol an ideal tool for investigating circadian rhythm. According to a large population-based study, morning salivary cortisol is negatively associated with Body Mass Index (BMI) and waist circumference, 5 with males showing a higher secretion rate than females.…”