Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.

Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements. Of 162 enrolled patients, baseline LNSC was measured in 93. Sixty-seven patients had levels above the upper limit of normal (ULN); median baseline levels were 19.7 and 20.7 nmol/L in the groups subsequently randomized to 600 μg (n = 40) and 900 μg (n = 27), respectively. Median LNSC levels decreased from baseline to month 12; median changes in patients who had baseline LNSC > ULN in the 600 and 900 μg groups were -13.4 nmol/L (-52.6 %; n = 19) and -11.8 nmol/L (-56.1 %; n = 14), respectively. LNSC normalized at months 6 and 12 in 25/67 (37.3 %) and 13/67 (19.4 %) patients, respectively; 10/25 and 8/13 patients also had normalized UFC, and 7/25 and 4/13 had partial UFC control (UFC > ULN and ≥50 % decrease from baseline). There was a moderate correlation (r = 0.55) on the log scale between individual patient LNSC and UFC values when all time points were pooled. Pasireotide decreased LNSC levels during 12 months of treatment. Salivary cortisol may be a simple, convenient biomarker for assessing treatment response in patients with Cushing's disease.
Competing Interests: J.W.F: Investigator and consultant for Novartis; investigator and consultant for Corcept; M.F.: Research grants to the Oregon Health & Science University from Cortendo, Ipsen, Novartis and Pfizer; occasional scientific consultant for Cortendo, Genentech and Novartis; J.N.P.: Investigator and consultant for Novartis and HRA Pharma; S.P.: Investigator and consultant for Novartis and Ipsen; R.P.: Principal investigator with grants from Novartis; research grants from Novartis, Viropharma, Pfizer and IBSA; lecture fees from Novartis and Pfizer; occasional consultant for Novartis, Ipsen, Italfarmaco, Pfizer, Ferring and Viropharma; A.K.: Employee of Novartis; A.M.P.: Employee of Novartis; B.M.K.B.: Principal investigator with grants to Massachusetts General Hospital from Novartis and Cortendo; occasional consultant to Novartis, Cortendo and HRA Pharma.