Successful Long-Term Treatment of Refractory Cushing’s Disease with High-Dose Mifepristone (RU 486)

An extremely ill patient, with Cushing’s syndrome caused by an ACTH-secreting pituitary macroadenoma, experienced complications of end-stage cardiomyopathy, profound psychosis, and multiple metabolic disturbances. Initially treated unsuccessfully by a combination of conventional surgical, medical, and radiotherapeutic approaches, he responded dramatically to high-dose long-term mifepristone therapy (up to 25 mg/kg·d). Treatment efficacy was confirmed by the normalization of all biochemical glucocorticoid-sensitive measurements, as well as by the significant reversal of the patient’s heart failure, the resolution of his psychotic depression, and the eventual unusual return of his adrenal axis to normal. His 18-month-long mifepristone treatment course was notable for development of severe hypokalemia that was attributed to excessive cortisol activation of the mineralocorticoid receptor, which responded to spironolactone administration. This case illustrates the efficacy of high-dose long-term treatment with mifepristone in refractory Cushing’s syndrome. The case also demonstrates the potential need for concomitant mineralocorticoid receptor blockade in mifepristone-treated Cushing’s disease, because cortisol levels may rise markedly, reflecting corticotroph disinhibition, to cause manifestations of mineralocorticoid excess.

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Successful Long-Term Treatment of Refractory Cushing's Disease with High-Dose Mifepristone (RU 486)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.86.8.3568 ◽

2001 ◽

Vol 86 (8) ◽

pp. 3568-3573 ◽

Cited By ~ 74

Author(s):

J. W. Chu

Keyword(s):

Cushing’S Disease ◽

Term Treatment ◽

Cushing's Disease ◽

High Dose ◽

Ru 486 ◽

Long Term Treatment

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Faculty Opinions recommendation of Cabergoline monotherapy in the long-term treatment of Cushing's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718270049.793490682 ◽

2014 ◽

Author(s):

Maria Fleseriu ◽

Shirley McCartney

Keyword(s):

Cushing’S Disease ◽

Term Treatment ◽

Cushing's Disease ◽

Long Term Treatment

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Long-term treatment of Cushing’s disease with pasireotide: 5-year results from an open-label extension study of a Phase III trial

Endocrine ◽

10.1007/s12020-017-1316-3 ◽

2017 ◽

Vol 57 (1) ◽

pp. 156-165 ◽

Cited By ~ 20

Author(s):

S. Petersenn ◽

L. R. Salgado ◽

J. Schopohl ◽

L. Portocarrero-Ortiz ◽

G. Arnaldi ◽

...

Keyword(s):

Cushing’S Disease ◽

Term Treatment ◽

Phase Iii ◽

Cushing's Disease ◽

Extension Study ◽

Open Label ◽

Phase Iii Trial ◽

Long Term Treatment ◽

Open Label Extension

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Prolonged remission after long-term treatment with steroidogenesis inhibitors in Cushing's syndrome caused by ectopic ACTH secretion

Acta Endocrinologica ◽

10.1530/eje-11-0949 ◽

2012 ◽

Vol 166 (3) ◽

pp. 531-536 ◽

Cited By ~ 13

Author(s):

S T Sharma ◽

L K Nieman

Keyword(s):

Cushing’S Syndrome ◽

Cushing's Syndrome ◽

Term Treatment ◽

Sustained Remission ◽

Ectopic Acth ◽

Ectopic Acth Secretion ◽

Free Cortisol ◽

Long Term Treatment ◽

History Of

Spontaneous remission is rare in ectopic ACTH syndrome (EAS). We describe four patients with presumed EAS in whom long-term treatment with steroidogenesis inhibitors was followed by prolonged remission of hypercortisolemia. Biochemical testing was consistent with EAS, but imaging failed to identify a tumor. Patients were treated with ketoconazole alone or with mitotane and/or metyrapone to control hypercortisolemia. Dexamethasone was added when a block and replace strategy was used. Treatment with steroidogenesis inhibitors for 3–10 years in these patients was followed by a prolonged period of remission (15–60 months). During remission, the first patient had an elevated ACTH, low cortisol and 24-h urinary free cortisol (UFC), and adrenal atrophy on computerized tomography scan during remission, suggesting a direct toxic effect on the adrenal glands. Cases 2 and 3 had normal to low ACTH levels and low-normal UFC, consistent with an effect at the level of the ectopic tumor. They did not have a history of cyclicity and case 3 has been in remission for ∼5 years, making cyclic Cushing's syndrome less likely. Case 4, with a history of cyclic hypercortisolism, had normal to slightly elevated ACTH levels and low-normal UFC during remission. The most likely etiology of remission is cyclic production of ACTH by the ectopic tumor. Spontaneous and sustained remission of hypercortisolemia is possible in EAS after long-term treatment with steroidogenesis inhibitors; a drug holiday may be warranted during chronic therapy to evaluate this. The pathophysiology remains unclear but may involve several different mechanisms.

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Cushing’s Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century

Hormone and Metabolic Research ◽

10.1055/a-0580-0460 ◽

2018 ◽

Vol 50 (04) ◽

pp. 280-289 ◽

Cited By ~ 2

Author(s):

Anelia Nankova ◽

Maria Yaneva ◽

Atanaska Elenkova ◽

Dimitar Tcharaktchiev ◽

Marin Marinov ◽

...

Keyword(s):

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Remission Rate ◽

Treatment Strategies ◽

Cushing's Syndrome ◽

New Drugs ◽

Cushing's Disease ◽

Treatment Modalities ◽

Tertiary Center

AbstractCushing’s syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients – the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing’s disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing’s disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

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Support Needs of Patients with Cushing’s Disease and Cushing’s Syndrome: Results of a Survey Conducted in Germany and the USA

International Journal of Endocrinology ◽

10.1155/2018/9014768 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Ilonka Kreitschmann-Andermahr ◽

Sonja Siegel ◽

Christa Gammel ◽

Karen Campbell ◽

Leslie Edwin ◽

...

Keyword(s):

Medical Care ◽

Cushing’S Syndrome ◽

Cushing’S Disease ◽

Disease Burden ◽

Cushing's Syndrome ◽

Cushing's Disease ◽

Support Needs ◽

Cross Sectional ◽

Patient Support Group

Background. Cushing’s disease (CD) and Cushing’s syndrome (CS) are chronic illnesses, characterized by symptoms of prolonged hypercortisolism, which often changes to hypocortisolism after successful treatment. In view of the high disease burden of CD/CS patients and long-term impaired quality of life, the present survey was conducted to gain information about subjective illness distress and patients’ specific needs in terms of supportive measures beyond medical interventions. Patients and Methods. Cross-sectional questionnaire study including patients with CD treated in 2 German neurosurgical tertiary referral centers and CD/CS patient members of a US-based patient support group completed a survey inquiring about disease burden, coping strategies, and support needs. Additionally, the degree of interest in different offers, e.g., internet-based programs and seminars, was assessed. Results. 84 US and 71 German patients answered the questionnaire. Patients in both countries indicated to suffer from Cushing-related symptoms, reduced performance, and psychological problems. 48.8% US patients and 44.4% German patients stated that good medical care and competent doctors helped them the most in coping with the illness. US patients were more interested in support groups (p=0.035) and in courses on illness coping (p=0.008) than the German patients, who stated to prefer brochures (p=0.001). 89.3% of US patients would attend internet-based programs compared to 75.4% of German patients (p=0.040). There were no differences between groups for the preferred duration of and the willingness to pay for such a program, but US patients would travel longer distances to attend a support meeting (p=0.027). Conclusion. Patients in both countries need skilled physicians and long-term medical care in dealing with the effects of CD/CS, whereas other support needs differ between patients of both countries. The latter implies that not only disease-specific but also culture-specific training programs would need to be considered to satisfy the needs of patients in different countries.

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