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Salivary cortisol biomarker may improve glucocorticoid therapy management
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In patients with adrenal insufficiency, salivary cortisol rhythm may serve as a useful biomarker to evaluate the adequacy of glucocorticoid replacement, according to findings from a proof-of-concept study reported in Clinical Endocrinology.
The well-being of patients with adrenal insufficiency depends on optimized glucocorticoid therapy, as undertreatment could induce chronic fatigue and lead to life-threatening adrenal crisis, and overtreatment may have negative, long-term metabolic and cardiovascular consequences, Filippo Ceccato, MD, a doctoral student at the University Hospital of Padova, Italy, and colleagues wrote in the study background.
“Many methods have been proposed to reliably monitor the quality of replacement therapy (clinical evaluation, urinary free cortisol, serum cortisol samples), but there is still no consensus about their effectiveness in clinical practice,” the researchers wrote. “Measurement of salivary cortisol is increasingly being used: It is an innovative method, allowing evaluation of the free hormone fraction in a noninvasive and stress-free sampling; moreover, saliva collection is easy to handle for outpatients.”
Ceccato and colleagues analyzed data from 19 patients with adrenal insufficiency (serum cortisol 138 nmol/L at diagnosis) on a stable glucocorticoid dose in a twice-daily regimen for at least 1 year before baseline. Before the study, all patients were taking a substitutive glucocorticoid dose at a higher-than-normal cortisol production rate ( 11 mg/m²) based on body surface area. Patients provided six saliva samples throughout the day, from before taking the morning glucocorticoid dose until bedtime, at baseline after a glucocorticoid dose reduction ( 5 mg hydrocortisone) and again at 1 year. Researchers measured daily cortisol exposure by calculating the area under the curve and conducted similar analysis in a cohort of 120 healthy adults (69 women; mean age, 43 years) as controls.
After at least 1 year (median, 14 months), median hydrocortisone equivalents decreased from the baseline 25 mg per day to 15 mg per day. After a reduction in glucocorticoid therapy dose, patients showed no signs or symptoms of adrenal insufficiency, and no adrenal crises were reported during the observation period. Two patients temporarily increased their glucocorticoid dose for 1 week due to illness.
When comparing baseline cortisol values with values at 1 year, researchers found that salivary cortisol concentrations decreased in the middle part of the day and in late evening, as did diastolic blood pressure, which fell from a mean of 87.5 mm Hg to 80 mm Hg from baseline to 1 year. Researchers also observed a global improvement in health-related quality of life between baseline and 1 year, assessed via questionnaires.
Researchers compared the 90th percentile of AUC for salivary cortisol levels in the control group with the adrenal insufficiency cohort and found that 12 patients (63%) had a baseline AUC greater than the 90th percentile, in the range of overtreatment. Of these 12 patients, four demonstrated a normalization of the AUC from baseline to 1 year, with a final daily cortisol exposure below the 90th percentile, according to researchers.
“At the end of the study, half of the patients had a daily cortisol exposure similar to healthy controls,” the researchers wrote.
They called the results encouraging but noted that optimization of glucocorticoid therapy in patients with adrenal insufficiency is still a challenge and that physicians must also consider drug absorption and metabolism, binding protein saturation and polymorphisms of the glucocorticoid receptor, among other factors.
“We suggest that multiple daily salivary cortisol collections could be considered to assess the adequacy of cortisol replacement therapy in patients with [adrenal insufficiency], in order to reduce their [glucocorticoid] dose and to ameliorate cardiovascular and metabolic parameters.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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