Endocrine Abstracts (2013) 32 P853 | DOI: 10.1530/endoabs.32.P853

Evaluation of late-night salivary cortisol during a Phase III study with pasireotide in patients with Cushing's disease

John Newell-Price1, Stephan Petersenn2, Rosario Pivonello3, James Findling4, Maria Fleseriu5, Andrew Trovato6, Gareth Hughes7, Monica Ligueros-Saylan7 & Beverly Biller8

1University of Sheffield, Sheffield, UK; 2ENDOC Center for Endocrine Tumors, Hamburg, Germany; 3Federico II University, Naples, Italy; 4Medical College of Wisconsin, Milwaukee, Wisconsin, USA; 5Oregon Health & Science University, Portland, Oregon, USA; 6Novartis Pharma AG, Basel, Switzerland; 7Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 8Massachusetts General Hospital, Boston, Massachusetts, USA.

Introduction: Measurement of salivary cortisol is a simple, convenient, accurate and reproducible technique with potential value during the diagnosis/management of hypercortisolism. Current analysis evaluates changes in late-night salivary cortisol (LNSC) during pasireotide treatment in patients with Cushing’s disease (CD).

Methods: A 12 m, Phase III study enrolled 162 adults with confirmed de novo or persistent/recurrent CD who were randomized to pasireotide 600 μg/900 μg s.c. bid. LNSC assessment (assay: cortisol ELISA RE52611, IBL-Hamburg GmbH, Germany) was an exploratory objective based on a single, optional measurement at midnight ±1 h on the same day as one of the 24-h UFC measurements. UFC control: UFC≤ULN; partial UFC control: UFC>ULN and ≥50% decrease from baseline.

Results: Baseline LNSC was measured in 93 patients; median levels were 17.3 and 10.3 nmol/l in the 600 μg (n=48) and 900 μg (n=45) dose groups (normal range 0.83–8.3). After 6 m, median levels decreased by 4.9 nmol/l (26.5% (95% CI −44.8, 39.3)) and 2.4 nmol/l (41.8% (95% CI −43.7, 34.0)) in the 600 μg/900 μg groups, respectively. LNSC was normalized at 6 m in 25/67 (37.3%) patients with baseline LNSC>ULN, comprising 16/40 (40.0%) and 9/27 (33.3%) patients in the 600 μg/900 μg groups, respectively. 10/25 patients with normalized LNSC at 6 m also had normalized UFC; seven had partial UFC control. Overall median LNSC decreases at 12 m were 7.2 nmol/l (42.2% (95% CI −40.8, 18.3)) and 1.6 nmol/l (26.1% (95% CI −41.1, 13.5)) in the 600 μg/900 μg groups, respectively. In both groups LNSC decreased in UFC controlled/partially controlled patients and increased in uncontrolled patients; patient numbers within each UFC control subgroup were low. An exploratory analysis demonstrated weak linear correlation (r=0.2), but moderate correlation (r=0.5) on the log scale between LNSC and UFC when all time points were pooled; the linear correlation was strong (r=0.9) at baseline.

Conclusions: Pasireotide decreased LNSC levels during 12 m of treatment. Salivary cortisol may be a simpler and more convenient biomarker than 24-h UFC to assess hypercortisolism patients with CD; further studies are required.