Increased long‐term remission after adequate medical cortisol suppression therapy as presurgical treatment in <scp>C</scp>ushing's disease

Bosch, Oscar F C van den; Stades, Aline M.E.; Zelissen, Pierre

doi:10.1111/cen.12286

Cited by 29 publications

(34 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These percentages rose to 7.1-22.7% (mean, 14.5%; median, 14.1%) when considering the population of patients initially responsive to treatment (494,501,502,507,508).…”

Section: Ketoconazolementioning

confidence: 96%

“…Five studies have evaluated the efficacy and safety of ketoconazole treatment in a relatively large number of patients, specifically, more than 10 patients, for a sufficiently long period of follow-up, specifically a mean and/or median follow-up of at least 6 months (494,501,502,507,508). These studies included a total number of 310 patients with CD; however, the real total number of different patients is likely 272, since 38 of these patients were apparently included in two different studies.…”

Section: Ketoconazolementioning

confidence: 99%

“…Considering these five major studies, ketoconazole has been administered at dosages ranging from 200 to 1200 mg/d (mean, 673.9 mg/d; median, 620 mg/d), with a follow-up ranging from 0.03 to 156 months (mean, 12.6 mo; median, 7.5 mo). According to the results of these studies, ketoconazole treatment controlled cortisol secretion in 44.7% to 92.9% of patients, with mean and median response rates of 64.3% and 50%, respectively (494,501,502,507,508). Table 9 summarizes the results of the main studies evaluating the outcome of ketoconazole therapy in CD.…”

Section: Ketoconazolementioning

confidence: 99%

“…In July 2013, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) gave strong warnings about the use of ketoconazole as an antifungal agent, due to its potential for hepatotoxicity. Although fatal hepatitis is a very rare event during ketoconazole treatment for CS, an increase in liver enzymes is frequently observed, ranging from 2.6 to 18.7% of cases in the major studies (494,501,502,507,508). Generally, this increase occurred at the beginning of treatment and normalized a few months after withdrawal.…”

Section: Ketoconazolementioning

confidence: 99%

“…Treatment with metyrapone in CD has been documented in case reports (525)(526)(527) and in five main studies including a total of 120 patients with CD (506,507,524,528,529). In these studies, the dosage of metyrapone ranged from 500 to 6000 mg/d (mean, 2127.5 mg/d; median, 1750 mg/d), with a follow-up ranging from 0.25 to 66 months (mean, 8.7 mo; median, 5.5 mo).…”

Section: Metyraponementioning

confidence: 99%

See 4 more Smart Citations

The Treatment of Cushing's Disease

et al. 2015

View full text Add to dashboard Cite

Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment. Patients with persistent or recurrent CD require additional treatments, including pituitary radiotherapy, adrenal surgery, and/or medical therapy. Pituitary radiotherapy is effective in controlling cortisol excess in a large percentage of patients, but it is associated with a considerable risk of hypopituitarism. Adrenal surgery is followed by a rapid and definitive control of cortisol excess in nearly all patients, but it induces adrenal insufficiency. Medical therapy has recently acquired a more important role compared to the past, due to the recent employment of novel compounds able to control cortisol secretion or action. Currently, medical therapy is used as a presurgical treatment, particularly for severe disease; or as postsurgical treatment, in cases of failure or incomplete surgical tumor resection; or as bridging therapy before, during, and after radiotherapy while waiting for disease control; or, in selected cases, as primary therapy, mainly when surgery is not an option. The adrenal-directed drug ketoconazole is the most commonly used drug, mainly because of its rapid action, whereas the glucocorticoid receptor antagonist, mifepristone, is highly effective in controlling clinical comorbidities, mainly glucose intolerance, thus being a useful treatment for CD when it is associated with diabetes mellitus. Pituitary-directed drugs have the advantage of acting at the site responsible for CD, the pituitary tumor. Among this group of drugs, the dopamine agonist cabergoline and the somatostatin analog pasireotide result in disease remission in a consistent subgroup of patients with CD. Recently, pasireotide has been approved for the treatment of CD when surgery has failed or when surgery is not an option, and mifepristone has been approved for the treatment of Cushing's syndrome when associated with impairment of glucose metabolism in case of the lack of a surgical indication. Recent experience suggests that the combination of different drugs may be able to control cortisol excess in a great majority of patients with CD.

show abstract

“…These percentages rose to 7.1-22.7% (mean, 14.5%; median, 14.1%) when considering the population of patients initially responsive to treatment (494,501,502,507,508).…”

Section: Ketoconazolementioning

confidence: 96%