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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 ?g 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 ?g (n = 40) and 900 ?g (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 ?g 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.

SUBMITTER: Findling JW

PROVIDER: S-EPMC5083774 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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

Findling James W JW Fleseriu Maria M Newell-Price John J Petersenn Stephan S Pivonello Rosario R Kandra Albert A Pedroncelli Alberto M AM Biller Beverly M K BM

Endocrine 20160521 2

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 fre ...[more]

PMID: 27209465

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Project description:PurposeCushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia.MethodsClinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed.ResultsThe frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3-67.0 %) than in patients with CD treated with pasireotide SC (68.4-73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791-799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875-884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320-326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914-924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues.ConclusionsDisease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly. Hyperglycemic effects associated with pasireotide have a predictable pattern, can be managed with antidiabetic agents, and are reversible upon discontinuation.

Project description:BackgroundDifferences in the expression of oxidative stress (OS) markers between female patients with temporomandibular disorders (TMD) and healthy individuals indicate that OS plays a role in the pathogenesis of TMD. Because chronic exposure to stress generates oxidative damage during continuous stimulation of the hypothalamic-pituitary-adrenal axis, we expected that higher levels of cortisol might be associated with higher oxidative damage. Our aim was to test the association between OS markers, stress perception, and salivary cortisol (SC) in chronic, female TMD patients. We tracked changes in OS markers and SC during occlusal splint therapy in order to evaluate the influence of treatment on oxidative status. We hypothesized that the effects of TMD therapy would differ among individuals depending on the source and intensity of pain.MethodsSixteen female patients were recruited, and 12 finished the study. Clinical assessment and saliva sampling were performed at the baseline and follow-up appointments. Repeated measures analysis of variance and Pearson's correlation were used for analyzing the data.ResultsAfter 3 months, a significant reduction in afternoon total antioxidant capacity (TAC) was observed (p < 0.05). A significant reduction in afternoon malondialdehyde (MDA) (p = 0.021) and a decrease in afternoon MDA to superoxide dismutase ratios (p = 0.017) were present in high-intensity pain patients. At baseline, higher levels of perceived stress were significantly associated with higher morning cortisol (ρ = 0.67). At the end of the therapy, reduced perceived stress was positively correlated with morning SC changes when considering all TMD patients, but the association between perceived stress with OS markers was present only in myofascial pain (MP) group. The effect of treatment on the self-perceived quality of life was more pronounced in female MP patients while the reduction of spontaneous pain was significantly greater in high-intensity pain patients.ConclusionOur data indicate that occlusal splint therapy in female TMD patients contributes to increasing their capacity to remove free radicals. The question remains whether or not TAC decreases in this process as a result of avoiding unnecessary processes, once the increase in antioxidants effectively compensates for OS. The intensity and the source of pain should be considered important factors in future investigations evaluating salivary OS markers and their association with perceived stress and SC in TMD patients.Trial registrationClinicalTrials.gov NCT03029494 . Registered on 2017-01-19.

Dataset Information

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

Publications

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

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