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Endocrine Abstracts (2022) 81 P405 | DOI: 10.1530/endoabs.81.P405

ECE2022 Poster Presentations Pituitary and Neuroendocrinology (127 abstracts)

Impact of urinary and late-night salivary cortisol levels on clinical signs of hypercortisolism and quality of life in patients with Cushing’s disease treated with osilodrostat

John Newell-Price 1 , Maria Fleseriu 2 , Rosario Pivonello 3 , Richard Feelders 4 , Andre Lacroix 5 , Richard Auchus 6 , Andrea Piacentini 7 , Alberto Pedroncelli 8 & Beverly M.K. Biller 9

1The Medical School, University of Sheffield, Department of Oncology and Metabolism, Sheffield, United Kingdom; 2Oregon Health & Science University, Pituitary Center, Departments of Medicine and Neurological Surgery, Portland, OR, United States; 3Università Federico II di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Naples, Italy; 4Erasmus Medical Center, Department of Internal Medicine, Endocrine Section, Rotterdam, Netherlands; 5Centre hospitalier de l’Université de Montréal, Montreal, Canada; 6University of Michigan, Ann Arbor, Division of Metabolism, Endocrinology and Diabetes, Departments of Internal Medicine and Pharmacology, Ann Arbor, MI, United States; 7Recordati SpA, Milan, Italy; 8Recordati AG, Basel, Switzerland; 9Massachusetts General Hospital, Neuroendocrine and Pituitary Tumor Clinical Center, Boston, MA, United States

Background: 24-h mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels are complementary parameters recommended for screening and monitoring treatment response in patients with Cushing’s disease (CD). In the published core period of the Phase III LINC 3 study (NCT02180217), therapy with osilodrostat (potent oral 11β-hydroxylase inhibitor) produced rapid, sustained reductions in mUFC and LNSC alongside improvements in clinical signs of hypercortisolism in patients with CD. Here, we explored these improvements by mUFC and/or LNSC control.

Methods: The core LINC 3 study enrolled 137 adults with CD and mUFC >1.5xULN who received open-label osilodrostat over 48 weeks (W; starting dose: 2 mg twice daily; maximum: 30 mg twice daily); eligible patients were randomised in an 8W placebo-controlled, withdrawal period (W26–34). mUFC (three-sample average; normal 11||138 nmol/24h) and LNSC (single sample; normal ≤2.5 nmol/l) were assessed centrally by liquid chromatography-tandem mass spectrometry. Cardiovascular/metabolic-related parameters, physical features (rating: 0=absent; 1=mild; 2=moderate; 3=severe), and CushingQoL and Beck Depression Inventory II (BDI-II) scores were also evaluated. Data were recorded at baseline and regularly until W48. Analyses are presented for patients with both mUFC and LNSC assessments, defined as: both mUFC+LNSC controlled, only mUFC controlled, only LNSC controlled, and both mUFC+LNSC uncontrolled. Control was defined as ≤ULN.

Results: Of evaluable patients at baseline (n=87), 74 (85.1%) had both mUFC+LNSC uncontrolled. At W48, 38 patients (54.3%) had both mUFC+LNSC controlled, 21 (30.0%) had only mUFC controlled, 3 (4.3%) had only LNSC controlled, and 8 (11.4%) had both mUFC+LNSC uncontrolled. Mean improvements from baseline to W48 in cardiovascular/metabolic-related parameters were generally greater in patients with both mUFC+LNSC controlled than patients with only mUFC or LNSC controlled or both mUFC+LNSC uncontrolled, respectively: weight, ||5.9, ||3.3, ||2.2, –3.8 kg; systolic blood pressure, ||14.4, ||8.0, ||7.4, ||3.0 mmHg; diastolic blood pressure, –8.6, ||4.8, ||8.2, ||4.0 mmHg; fasting plasma glucose, ||0.9, ||0.3, ||0.8, ||0.6 mmol/l. CushingQoL/BDI-II scores improved from baseline to W48 irrespective of mUFC and/or LNSC control. Patients with both mUFC+LNSC controlled or only mUFC controlled had the greatest proportion with improved physical manifestations of hypercortisolism (facial rubor, striae, fat pads, bruising, hirsutism [females], muscle atrophy).

Discussion: After 48W of osilodrostat treatment, most evaluable patients had both mUFC+LNSC controlled or only mUFC controlled. Improvements in clinical signs of hypercortisolism and health-related quality of life occurred irrespective of mUFC and/or LNSC control; however, improvements were greater in patients with both mUFC+LNSC controlled for some clinical outcomes.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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