Introduction: Pasireotide is a promising treatment option for patients with Cushings disease (CD). The measurement of salivary cortisol is useful for diagnosing hypercortisolism and monitoring patients with CD following pituitary surgery. It may also be a better index of cortisol secretion than serum cortisol or urinary free cortisol (UFC). We investigated the value of salivary cortisol in monitoring short-term efficacy of pasireotide in patients with CD.
Methods: Seven patients (five females, two males; mean age 35.3±7.4 years) received pasireotide 600 μg bid for 15 days in the Phase II study CSOM230B2208. Morning and midnight salivary cortisol, ACTH and morning serum cortisol were assessed at baseline and after 1, 5, 12, and 15 days of treatment. UFC was determined at baseline and day 15.
Results: On day 15, morning salivary cortisol had decreased in all patients; overall mean decrease from baseline was 70% (27.7±30.88.2±7.7 mmol/l). Midnight salivary cortisol had decreased in six patients and normalized in two; overall mean reduction from baseline was 50% (27.2±38.613.4±15.4 mmol/l). Decreases in morning and midnight salivary cortisol were observed from day 1 (mean reduction from baseline of 34 and 20% respectively) and persisted until day 15; the greatest decrease was on day 5 (mean reduction of 70 and 58%, respectively). At day 15, mean UFC had decreased from baseline by 65% (1711±1941593±360 mmol/24 h). UFC was normalized in one patient (14%), who also had normalized midnight salivary cortisol, thereby restoring cortisol rhythm. Changes in ACTH and serum cortisol were similar to those of salivary cortisol.
Conclusions: Pasireotide rapidly reduced and normalized salivary cortisol. Salivary cortisol may be a simple, non-invasive biomarker to assess immediate response to pasireotide in patients with CD, particularly to determine whether cortisol rhythm is normalized in patients with normalized UFC levels. More studies are necessary to confirm these preliminary results.