SFEBES2018 Poster Presentations Adrenal and steroids (38 abstracts)
11β-HSD type 1 inhibitor ameliorates metabolic disorders associated with hypercortisolemia: A clinical trial to assess its safety and efficacy in Japanese patients with refractory Cushing’s syndrome and subclinical Cushing’s syndrome
Satoko Oda 1 , Hiromi Nagata 1 , Kenji Ashida 2 , Shohei Sakamoto 1 , Makiko Uchiyama 3 , Ayako Nagayama 2 , Shimpei Iwata 2 , Koji Todaka 3 , Yoichi Nakanishi 3 & Masatoshi Nomura 2
1Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan; 3Center for Clinical and Translational Research of Kyushu University Hospital, Fukuoka, Japan.
Cushing’s syndrome (CS) and subclinical Cushing’s syndrome (SCS) show poor prognosis due to hypercortisolemia, which causes metabolic disorders, such as diabetes mellitus, hypertension, dyslipidemia, and osteoporosis. Aiming to improve prognosis and develop a novel treatment for these refractory diseases, we have been constructing a patient registry of CS and SCS founded on a multicenter database at Kyushu University hospital and related facilities since 2001. CS included Cushing’s disease, adrenal CS, and ectopic ACTH syndrome. The proposed diagnostic criteria for adrenal SCS has been described (Akehi, et al. Endocr J. 2013, 60: 903–12). First, we performed a prognostic survey using the registry comprising 112 patients (40% CS and 60% SCS). The prevalence of complications of glucose impairment, hypertension, and dyslipidemia was 75, 48, and 23% in CS and 72, 49, and 31% in SCS, respectively. Despite surgery, 70% of CS patients were not cured. In addition, 59% of SCS patients have not undergone surgery. Consequently, a considerable number of patients still need treatment for hypercortisolemia. Second, we performed an investigator-initiated phase I/IIa clinical trial to assess the safety and efficacy of a 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor in patients with refractory CS and SCS between 2016 and 2018 (Registration ID: UMIN000024482). Although 11β-HSD1 bidirectionally interconverts the inactive glucocorticoid cortisone and the active cortisol, it predominantly generates cortisol. Hypercortisolemia activates 11β-HSD1, which promotes the development of hypercortisolemia-related metabolic disorders. In the present study, 16 patients with refractory CS and SCS with impaired glucose tolerance were enrolled. Administration of 11β-HSD1 inhibitor for 24 weeks showed its safety and efficacy with reduction of urine 11α- and 11β-tetrahydrocortisol/11β-tetrahydrocortisone ratio by one-tenth. Inhibition of 11β-HSD1 activity is expected to be a new therapeutic approach for the patients with refractory CS and SCS.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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