Mifepristone: is there a place in the treatment of Cushing's disease?

Carmichael JD, Fleseriu M.

Source

Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA, john.carmichael@cshs.org.

Abstract

The purpose was to review the use of mifepristone in the treatment of Cushing's syndrome (CS) in the context of other recently published studies. We review the use of mifepristone, as published in the recent Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing's Syndrome (SEISMIC). We also review the multiple case reports and case series of mifepristone use in CS. A review of other medications used in the treatment of Cushing's disease (CD), including pasireotide and cabergoline also provides context for the discussion of the role of mifepristone in the treatment of CD. The results show that the treatment of CD has been primarily surgical with medical therapy reserved for adjuvant therapy when primary treatment fails or other therapies require time for optimal efficacy. Two recent large prospective studies, using pasireotide and mifepristone provide new clinical insights to the medical treatment of CD in particular. Mifepristone has been used to treat excessive cortisol production by blocking the action of cortisol at the level of the glucocorticoid receptor. Until recently, the majority of clinical experience with mifepristone on the treatment of excess cortisol was derived from case reports and small case series. Based on the SEISMIC study, mifepristone was FDA approved for hyperglycemia associated with CS. In conclusion the role of mifepristone in the treatment of CD remains one of adjuvant therapy. Its place among other choices for medical therapy has yet to be firmly established and an evidenced-based approach toward the use of novel medications in the treatment of CD has not been made. Selection of medication depends on drug approval and availability in individual countries and requires cautious assessment of potential adverse effects, consideration of patient comorbidities, and efficacy.

 

PMID: 23192246 [PubMed - as supplied by publisher]

Dr. Amir Hamrahian Answers Our Questions About Cushing's and Korlym

October 1, 2012 at 6:30 PM eastern, Dr. Amir Hamrahian will answer our questions about Cushing's, pituitary or adrenal issues and Korlym (mifepristone) in BlogTalkRadio at http://www.blogtalkradio.com/cushingshelp/2012/10/01/dr-amir-hamrahian-answers-our-questions

 

You may listen live at the link above.  The episode will be added to the Cushing's Help podcast after the show is over.  Listen to the podcasts by searching for Cushings in the iTunes podcast area or click here: http://itunes.apple.com/podcast/cushingshelp-cushie-chats/id350591438

 

Dr. Hamrahian has had patients on Korlym for about 4 years.

 

Please submit your questions below or email them to CushingsHelp@gmail.com before Sunday, September 30.

 

From Dr. Hamrahian's bio at http://my.clevelandclinic.org/staff_directory/staff_display.aspx?doctorid=3676

 

 

Amir Hamrahian, M.D. 

(216) 444-6568

Appointed: 2000

Request an Appointment

Department:Endocrinology, Diabetes and Metabolism

Location:Cleveland Clinic Main Campus
Mail Code F20 
9500 Euclid Avenue
Cleveland, OH 44195

Appointment:(216) 444-6568

Desk:(216) 445-8538

Fax:(216) 445-1656

Department:Brain Tumor and Neuro-Oncology Center

Location:Cleveland Clinic Main Campus
Mail Code R20 
9500 Euclid Avenue
Cleveland, OH 44195

Appointment:(216) 444-6568

Desk:(216) 445-8538

Fax:(216) 445-1656

Surgeon:

No

Treats:

Adults Only

Research & Publications †

( † Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Biographical Sketch

Amir H. Hamrahian, MD, is a Staff member in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic's main campus, having accepted that appointment in 2005. Prior to that appointment, he was also a clinical associate there for nearly five years. 

His clinical interests include pituitary and adrenal disorders.

Dr. Hamrahian received his medical degree from Hacettepe University in Ankara, Turkey, and upon graduation was a general practitioner in the provinces of Hamadan and Tehran, Iran. He completed an internal medicine residency at the University of North Dakota, Fargo, and an endocrinology fellowship at Case Western Reserve University and University Hospitals, Cleveland.

In 2003, he received the Teacher of the Year award from Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism. Dr. Hamrahian speaks three languages -- English, Turkish and Farsi -- and is board-certified in internal medicine as well as endocrinology, diabetes and metabolism. He is a member of the Endocrine Society, Pituitary Society and the American Association of Clinical Endocrinologists.

Education & Fellowships

Fellowship - University Hospitals of Cleveland

Endocrinology
Cleveland, OH USA
2000

Residency - University of North Dakota Hospital

Internal Medicine
Fargo, ND USA
1997

Medical School - Hacettepe University School of Medicine

Ankara Turkey
1991

Certifications

• Internal Medicine
• Internal Medicine- Endocrinology, Diabetes & Metabolism

Specialty Interests

Cushing syndrome, acromegaly, pheochromocytoma, prolactinoma, primary aldosteronism, pituitary disorders, adrenal tumor, adrenocortical carcinoma, MEN syndromes, adrenal disorders

Awards & Honors

• Best Doctors in America, 2007-2008 

Memberships

• Pituitary Society
• Endocrine Society
• American Association of Clinical Endocrinologists
• American Medical Association

Treatment & Services

• Radioactive Iodine Treatment
• Thyroid Aspiration
• Thyroid Ultrasound

Specialty in Diseases and Conditions

• Acromegaly
• Addison’s Disease
• Adrenal disorders
• Adrenal insufficiency
• Adrenal Insufficiency and Addison’s Disease
• Adrenal Tumors
• Adrenocortical Carcinoma
• Adrenoleukodystrophy (ALD)
• Amenorrhea
• Androgen Deficiency (Low Testosterone)
• Androgen Excess
• Calcium Disorders
• Carcinoid Syndrome
• Conn's Syndrome
• Cushing's Syndrome
• Empty sella
• Erectile Dysfunction
• Familial Multiple Endocrine Neoplasia
• Fasting hypoglycemia
• Flushing Syndromes
• Galactorrhea
• Goiter
• Growth hormone deficiency
• Growth hormone excess
• Gynecomastia
• Hirsutism
• Hyperaldosteronism
• Hyperandrogenism
• Hyperprolactinemia
• Hypertension - High Blood Pressure
• Hyperthyroidism
• Hypocalcemia
• Hypoglycemia
• Hypogonadism
• Hypoparathyroidism
• Hypophysitis
• Hypopituitarism
• Hypothyroidism
• Mastocytosis
• Menopause, Male
• Menstrual Disorders
• Paget's Disease
• Panhypopituitarism
• Parathyroid Cancer
• Parathyroid Disease and Calcium Disorders
• Pheochromocytoma
• Pituitary Cysts
• Pituitary Disorders
• Pituitary stalk lesions
• Pituitary Tumors
• Premenstrual Syndrome (PMS)
• Primary Hyperaldosteronism
• Primary Hyperparathyroidism
• Prolactin Excess States
• Prolactinoma
• Thyroid and pregnancy
• Thyroid Cancer
• Thyroid Disease
• Thyroid Nodule

Medical management of Cushing's disease: what is the future?

Fleseriu M, Petersenn S.

Source

Departments of Medicine and Neurological Surgery, Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.

Abstract

Cushing's disease (CD) is caused by a corticotroph, adrenocorticotropic-hormone (ACTH)-secreting pituitary adenoma resulting in significant morbidity and mortality. Transsphenoidal surgery is the initial treatment of choice in almost all cases.

Remission rates for microadenomas are good at 65-90 % (with an experienced neurosurgeon) but remission rates are much lower for macroadenomas. However, even after postoperative remission, recurrence rates are high and can be seen up to decades after an initial diagnosis. Repeat surgery or radiation can be useful in these cases, although both have clear limitations with respect to efficacy and/or side effects.

Hence, there is a clear unmet need for an effective medical treatment. Currently, most drugs act by inhibiting steroidogenesis in the adrenal glands. Most is known about the effects of ketoconazole and metyrapone. While effective, access to ketoconazole and metyrapone is limited in many countries, experience with long-term use is limited, and side effects can be significant. Recent studies have suggested a role for a pituitary-directed therapy with new multireceptor ligand somatostatin analogs (e.g., pasireotide, recently approved in Europe for treatment of CD), second-generation dopamine agonists, or a combination of both.

Mifepristone (a glucocorticoid receptor antagonist) is another promising drug, recently approved by the FDA for treatment of hyperglycemia associated with Cushing's syndrome. We review available medical treatments for CD with a focus on the two most recent compounds referenced above.

Our aim is to expand awareness of current research, and the possibilities afforded by available medical treatments for this mesmerizing, but often frightful disease.

PMID: 22674211 [PubMed - as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/22674211