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Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing's Syndrome
Abstract
CONTEXT: Cushing's syndrome (CS) is a disorder associated with significant morbidity and mortality due to prolonged exposure to high cortisol concentrations. OBJECTIVE: Our objective was to evaluate the safety and efficacy of mifepristone, a glucocorticoid receptor antagonist, in endogenous CS. DESIGN AND SETTING: We conducted a 24-wk multicenter, open-label trial after failed multimodality therapy at 14 U.S. academic medical centers and three private research centers. PARTICIPANTS: Participants included 50 adults with endogenous CS associated with type 2 diabetes mellitus/impaired glucose tolerance (C-DM) or a diagnosis of hypertension alone (C-HT). INTERVENTION: Mifepristone was administered at doses of 300-1200 mg daily. MAIN OUTCOME MEASURES: We evaluated change in area under the curve for glucose on 2-h oral glucose test for C-DM and change in diastolic blood pressure from baseline to wk 24 for C-HT. RESULTS: In the C-DM cohort, an area under the curve for glucose (AUC(glucose)) response was seen in 60% of patients (P < 0.0001). Mean ± sd glycated hemoglobin (HbA1c) decreased from 7.43 ± 1.52% to 6.29 ± 0.99% (P < 0.001); fasting plasma glucose decreased from 149.0 ± 75.7 mg/dl (8.3 ± 4.1 mmol/liter) to 104.7 ± 37.5 mg/dl (5.8 ± 2.1 mmol/liter, P < 0.03). In C-HT cohort, a diastolic blood pressure response was seen in 38% of patients (P < 0.05). Mean weight change was -5.7 ± 7.4% (P < 0.001) with waist circumference decrease of -6.78 ± 5.8 cm (P < 0.001) in women and -8.44 ± 5.9 cm (P < 0.001) in men. Overall, 87% (P < 0.0001) had significant improvement in clinical status. Insulin resistance, depression, cognition, and quality of life also improved. Common adverse events were fatigue, nausea, headache, low potassium, arthralgia, vomiting, edema, and endometrial thickening in women. CONCLUSIONS: Mifepristone produced significant clinical and metabolic improvement in patients with CS with an acceptable risk-benefit profile during 6 months of treatment.
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“Overt adrenal insufficiency is rare under treatment with mifepristone (326).”
From Adrenocortical carcinoma (2014) · cites this paper as [326]
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Treatment of Cushing's syndrome: an Endocrine Society clinical practice guideline
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“Glucocorticoid receptor antagonist In one study, Mifepristone, a glucocorticoid receptor antagonist and antiprogestin, led to an improvement in hypertension and/or diabetes in 40 and 60%, respectively, of 34 patients (141).”
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Metadata
- Authors
- Fleseriu, M., Biller, B. M. K., Findling, J. W., Molitch, M. E., Schteingart, D. E., Gross, C., on behalf of the SEISMIC Study Investigators, The SEISMIC Study Investigators include, Auchus, R., Bailey, T., Biller, B. M. K., Carroll, T., Colleran, K., Fein, H., Findling, J. W., Fleseriu, M., Hamrahian, A., Katznelson, L., Kerr, J., Kipnes, M., Kirschner, L., Koch, C., Lerman, S., Lyons, T., McPhaul, M., Molitch, M. E., Schteingart, D. E., Vaughan, T. B., & Weiss, R.
- Affiliations
- Corcept Therapeutics (United States) (US)
- The University of Texas Southwestern Medical Center (US)
- AMCR Institute (US)
- Massachusetts General Hospital (US)
- Medical College of Wisconsin (US)
- Oregon Health & Science University (US)
- Cleveland Clinic (US)
- Northwestern University (US)
- The Ohio State University Wexner Medical Center (US)
- University of Mississippi Medical Center (US)
- University of Michigan (US)
- University of Alabama at Birmingham (US)
- University of Chicago (US)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-06-01
- Volume
- 97
- Issue
- 6
- Pages
- 2039-2049
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2021271765
- Semantic Scholar
- 40d98664c0987b1bdf2cbb43dbea52247bf04f70
- Cited by
- 479
- References
- 45
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 22 · 2023: 28 · 2022: 33 · 2021: 29 · 2020: 30 · 2019: 41 · 2018: 35 · 2017: 35 · 2016: 38 · 2015: 45 · 2014: 39 · 2013: 39 · 2012: 16
- FWCI
- 35.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- mifepristone, Cushing's syndrome, glucocorticoid receptor antagonist, type 2 diabetes, impaired glucose tolerance, hypertension, glycemic control, HbA1c, insulin resistance, blood pressure, weight loss, waist circumference, adverse events, drug safety, quality of life, depression, cognitive function
- MeSH terms
- Adult, Antihypertensive Agents, Blood Glucose, Blood Pressure, Body Composition, Body Weight, Cushing Syndrome, Diabetes Mellitus, Type 2, Female, Hormone Antagonists, Humans, Hydrocortisone, Hypertension, Male, Middle Aged, Quality of Life, Quinolines, Receptors, Glucocorticoid, Urea, Mifepristone, Glucose Intolerance
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