ECE2023 Poster Presentations Pituitary and Neuroendocrinology (123 abstracts)
Impact of Surgery or Medical Treatment with the Selective Glucocorticoid Receptor Modulator Relacorilant on Hypercoagulopathy in Patients with Cushing Syndrome
Chiara Simeoli 1 , Nicola Di Paola 1 , Antonio Stigliano 2 , Pina Lardo 2 , Tara Kearney 3 , Emese Mezosi 4 , Ezio Ghigo 5 , Roberta Giordano 5 , Cary N. Mariash 6 , Diane Donegan 7 , Richard Feelders 8 , Austin Hand 9 , Andreas G. Moraitis 9 & Rosario Pivonello 1
1Università “Federico II” di Napoli, Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Naples, Italy; 2Sant’Andrea University Hospital, Sapienza University of Rome, Endocrinology, Rome, Italy; 3Salford Royal Foundation Trust, Manchester, United Kingdom; 4University of Pecs, Ist Department of Internal Medicine, Clinical Center, Pecs, Hungary; 5University of Turin, Division of Endocrinology, Diabetology and Metabolism, Turin, Italy; 6Indiana University and Indiana University Health, Indianapolis, United States; 7Indiana University School of Medicine, Indianapolis, United States; 8Erasmus Medical Center, Department of Internal Medicine, Division of Endocrinology, Rotterdam, Netherlands; 9Corcept Therapeutics Incorporated, Menlo Park, United States
In patients with Cushing syndrome (CS), hypercoagulability represents a significant concern, leading to elevated risk for thrombotic events. After curative surgery, hypercoagulability persists for several months; CS treatment guidelines recommend anticoagulation therapy for ≤ 3 months. In patients with Cushing disease, hemostatic parameters may even worsen after surgery, independent of surgical outcome; improvements begin ~3 months after successful surgery (Casonato et al. Blood Coagul Fibrinolysis 1999). This transient worsening may be due to increased inflammation—cortisol levels, and hence cortisol’s anti-inflammatory effects, decrease after successful surgery, leading to increased coagulation cascade activity, which normalizes over time. We evaluated the impact of surgery or treatment with the selective glucocorticoid receptor modulator relacorilant on the coagulation state in patients with CS in a retrospective, longitudinal, monocentric, surgical cohort study and an open-label phase 2 study of relacorilant (NCT02804750). In the surgical study, coagulation markers were assessed in 30 patients before curative surgery and during remission. In the relacorilant study, patients received relacorilant 100–200 mg for 12 weeks or relacorilant 250–400 mg for 16 weeks; coagulation markers were assessed in 34 patients. In the surgical study, baseline mean 24-hour urinary free cortisol (UFC) was 615.6 mg/day (by immunoassay; 2.1× upper limit of normal [ULN]); mean and median time to hemostasis assessment after remission were 6.2 and 6 months. Significant mean changes from baseline were observed in activated partial thromboplastin time (aPTT; +2.0 seconds, P=0.031), factor VIII (fVIII; 24.2%, P=0.044), and von Willebrand factor (vWF; 20.6%, P=0.018); platelet count was unchanged. In the relacorilant study, baseline mean UFC was 211.9 mg/day (by tandem mass spectrometry; 4.2× ULN). Similar to the surgical study, significant mean changes from baseline to last observed visit were reported in aPTT (+1.5 seconds, P=0.046), fVIII (-18.9%, P=0.022), and platelet count (68.8*109/l, P<0.0001); vWF was unchanged. Significant improvements in other coagulation factors (eg, fIX and fX) were seen in patients with abnormal baseline values. These studies showed that coagulation markers in patients with CS improve 6 months after curative surgery, and relacorilant treatment may have similar effects after 3–4 months. Transient increases in fVIII immediately after surgery were absent with relacorilant, where negative mean changes from baseline were seen throughout the study. This is presumably due to the less abrupt reduction of cortisol activity with relacorilant compared to surgery. Relacorilant’s effects on hypercoagulopathy support further investigation of preoperative use and in patients with CS who are ineligible for surgery.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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