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Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.

ABSTRACT: Objective:Monitoring of patients with Cushing's disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing's disease. Design:Exploratory analysis evaluating LNSC during a Phase III study of long-acting pasireotide in Cushing's disease (clinicaltrials.gov: NCT01374906). Methods:Mean LNSC (mLNSC) was calculated from two samples, collected on the same days as the first two of three 24-h urine samples (used to calculate mean UFC [mUFC]). Clinical signs of hypercortisolism were evaluated over time. Results:At baseline, 137 patients had evaluable mLNSC measurements; 91.2% had mLNSC exceeding the upper limit of normal (ULN; 3.2 nmol/L). Of patients with evaluable assessments at month 12 (n = 92), 17.4% had both mLNSC ?ULN and mUFC ?ULN; 22.8% had mLNSC ?ULN, and 45.7% had mUFC ?ULN. There was high variability in LNSC (intra-patient coefficient of variation (CV): 49.4%) and UFC (intra-patient CV: 39.2%). mLNSC levels decreased over 12 months of treatment and paralleled changes in mUFC. Moderate correlation was seen between mLNSC and mUFC (Spearman's correlation: ? = 0.50 [all time points pooled]). Greater improvements in systolic/diastolic blood pressure and weight were seen in patients with both mLNSC ?ULN and mUFC ?ULN. Conclusion:mUFC and mLNSC are complementary measurements for monitoring treatment response in Cushing's disease, with better clinical outcomes seen for patients in whom both mUFC and mLNSC are controlled.

SUBMITTER: Newell-Price J

PROVIDER: S-EPMC7003692 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.

Newell-Price John J Pivonello Rosario R Tabarin Antoine A Fleseriu Maria M Witek Przemysław P Gadelha Mônica R MR Petersenn Stephan S Tauchmanova Libuse L Ravichandran Shoba S Gupta Pritam P Lacroix André A Biller Beverly M K BMK

European journal of endocrinology 20200201 2

<h4>Objective</h4>Monitoring of patients with Cushing's disease on cortisol-lowering drugs is usually performed with urinary free cortisol (UFC). Late-night salivary cortisol (LNSC) has an established role in screening for hypercortisolism and can help to detect the loss of cortisol circadian rhythm. Less evidence exists regarding the usefulness of LNSC in monitoring pharmacological response in Cushing's disease.<h4>Design</h4>Exploratory analysis evaluating LNSC during a Phase III study of long ...[more]

PMID: 31804965

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Project description:ObjectiveThe objective of this systematic review was to evaluate the effectiveness and safety of pasireotide, cabergoline, ketoconazole, levoketoconazole, metyrapone, osilodrostat, and temozolomide for the treatment of Cushing's disease (CD).MethodsThe primary outcomes were the proportion of CD control, adverse events (AE), and reduction of urinary free cortisol. Search strategies were applied to Embase, Medline, and CENTRAL. Independent reviewers assessed the study eligibility, extracted data, and evaluated risk of bias. Standardized mean difference was calculated with 95% confidence interval (CI) for continuous data (i.e., pre- and post-intervention). Random meta-analyses for the proportion of CD control and AE were conducted.ResultsTwenty-nine controlled and non-controlled studies were included. No study with temozolomide and levoketoconazole and one study with osilodrostat fulfilled the inclusion criteria. The meta-analyses of proportion of CD control was 35% for cabergoline (95% CI: 27-43%, six studies, 141 participants), 44% for pasireotide (95% CI: 25-35%, eight studies, 522 participants), 41% for ketoconazole (95% CI: 36-46%, six studies, 450 participants), 66% for metyrapone (95% CI: 46-87%, four studies, 66 participants), and of 66.4% for osilodrostat (95% CI: 57.9, 74.3, 97 participants, one study). One study compared two different treatments (cabergoline vs. ketoconazole), and no statistical difference was observed in CD control (RR: 0.53, 95% CI: 0.15 to 1.87, 14 participants, very low certainty of evidence). The most frequent AE associated with pasireotide was hyperglycemia, dizziness and nausea with cabergoline and metyrapone, and elevated transaminases with ketoconazole.ConclusionThe superiority of one drug over another could not be determined due to lack of controlled studies, but the proportion of disease control identified in our meta-analysis may support clinical decision. New therapeutic options should be investigated due to the limited efficacy and tolerability of the currently available medical treatment for patients with Cushing's disease.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020205567, identifier CRD42020205567.

Dataset Information

Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.

Publications

Use of late-night salivary cortisol to monitor response to medical treatment in Cushing's disease.

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