A New Therapeutic Approach in the Medical Treatment of Cushing’S SYNDROME: GLUCOCORTICOID RECEPTOR BLOCKADE WITH MIFEPRISTONE

Fleseriu, Maria; Molitch, Mark E.; Gross, Coleman; Schteingart, D.E.; Vaughan, T. Brooks; Biller, Beverly M. K.

doi:10.4158/ep12149.ra

Cited by 56 publications

(66 citation statements)

References 63 publications

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“…Treatment with mifepristone can then be resumed at a lower dose once the clinician has determined that excessive glucocorticoid receptor antagonism is resolved by monitoring and asking the patient about any clinical signs and symptoms that may be present. Because of the long half-life of mifepristone (85 hours) (25), it may take 2 or more weeks for resolution to occur (23,26).…”

Section: Discussionmentioning

confidence: 99%

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Yuen

Williams

Kushner³

et al. 2015

Endocrine Practice

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Section: Discussionmentioning

confidence: 99%

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Yuen

Williams

Kushner³

et al. 2015

Endocrine Practice

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“…All are currently used as an off-label treatment for Cushing syndrome (CS). 5,10,[30][31][32] Ketoconazole and metyrapone are most frequently used; but there are no prospective studies of these agents in CD patients. 18 Chronic treatment can be limited by side effects such as hepatotoxicity (ketoconazole) and increased androgen and mineralocorticoid production (metyrapone).…”

Section: Adrenal Steroidogenesis Inhibitorsmentioning

confidence: 99%

“…It takes approximately 2 weeks to clear mifepristone from the circulation after dosing cessation. 30,35 Mifepristone use for refractory Cushing (but rarely in CD) was initially described in case reports and series. 8,30,36 A large open-label, 24-week, multicenter trial (SEISMIC) studied 50 mifepristone-treated CS patients, 43 with CD.…”

Section: Glucocorticoid Receptor Blockermentioning

confidence: 99%

Medical Treatment of Cushing Disease

Fleseriu¹

2015

Endocrinology and Metabolism Clinics of North America

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“…However, it is also a competitive antagonist of glucocorticoid action at the glucocorticoid receptor (GR), prompting its development as a treatment of CS. [4][5][6][7] In a recent trial, the administration of mifepristone resulted in improvement in hypertension and hyperglycemia control in adults with CS. On the basis of this study, mifepristone was recently approved by the US Food and Drug Administration (FDA) for adults with endogenous CS and hyperglycemia.…”

mentioning

confidence: 99%

Mifepristone Treatment of Cushing’s Syndrome in a Pediatric Patient

Banerjee¹,

Marina

Katznelson

et al. 2015

Pediatrics

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Cushing's syndrome (CS) in the pediatric population is challenging to diagnose and treat. Although next-generation medical therapies are emerging for adults with CS, none are currently approved or used in children. Here we describe the first use of mifepristone, a glucocorticoid receptor antagonist, to treat CS in a pediatric subject. The patient, a 14-year-old girl with an 18-month history of metastatic neuroendocrine carcinoma, suffered from fatigue, profound myopathy, irritability, and depression. She was found to have hypertension, hypokalemia, and worsening control of her preexisting type 1 diabetes. In this report, we detail our clinical evaluation that confirmed CS caused by an ectopic adrenocorticotropic hormone secreting tumor. Surgical and radiation therapies were not pursued because of her poor functional status and limited life expectancy, and medical treatment of CS was indicated for symptom relief. Mifepristone treatment provided rapid improvement in glycemic control, insulin resistance, and hypertension as well as significant diminishment of her myopathy and fatigue. Hypokalemia was managed with an oral potassium replacement and dose escalation of spironolactone; no other significant adverse effects were observed. Despite successful palliation of Cushing's signs and symptoms, the patient died of progression of her cancer. This case demonstrates the safety and efficacy of mifepristone treatment in a pediatric patient with symptomatic, ectopic CS. We conclude that, in appropriate pediatric patients with CS, glucocorticoid receptor antagonism with mifepristone should be considered to control the effects of hypercortisolism and to improve quality of life.

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A New Therapeutic Approach in the Medical Treatment of Cushing’S SYNDROME: GLUCOCORTICOID RECEPTOR BLOCKADE WITH MIFEPRISTONE

Cited by 56 publications

References 63 publications

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Medical Treatment of Cushing Disease

Mifepristone Treatment of Cushing’s Syndrome in a Pediatric Patient

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