title: Late-night salivary cortisol may be valuable for assessing treatment response in patients with Cushing's disease: 12-month, Phase III pasireotide study.
abstract: 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.
authors.affiliation: Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, W129 N7055 Northfield Drive Suite A-203, Menomonee Falls, Milwaukee, WI, 53051, USA. jfindling@mcw.edu.
authors.forename: James W
authors.initials: JW
authors.lastname: Findling
authors.affiliation: Departments of Medicine and Neurological Surgery, Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Fleseriu
authors.affiliation: The Medical School, University of Sheffield, Sheffield, UK.
authors.forename: John
authors.initials: J
authors.lastname: Newell-Price
authors.affiliation: ENDOC Center for Endocrine Tumors, Hamburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Petersenn
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Endocrinologia e Metabolismo, Università Federico II di Napoli, Naples, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Albert
authors.initials: A
authors.lastname: Kandra
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pedroncelli
authors.affiliation: Neuroendocrine Clinical Center, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002940:Circadian Rhythm / Q000502:physiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy* / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D012463:Saliva / Q000737:chemistry; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D013004:Somatostatin; C517782:pasireotide; D006854:Hydrocortisone
keywords: Cushing’s disease; Pasireotide; Salivary cortisol; Urinary free cortisol