Abstract
PurposeTo systematically review the effectiveness of medical treatment for Cushing’s syndrome in clinical practice, regarding cortisol secretion, clinical symptom improvement, and quality of life. To assess the occurrence of side effects of these medical therapies.MethodsEight electronic databases were searched in March 2017 to identify potentially relevant articles. Randomized controlled trials and cohort studies assessing the effectiveness of medical treatment in patients with Cushing’s syndrome, were eligible. Pooled proportions were reported including 95% confidence intervals.ResultsWe included 35 articles with in total 1520 patients in this meta-analysis. Most included patients had Cushing’s disease. Pooled reported percentage of patients with normalization of cortisol ranged from 35.7% for cabergoline to 81.8% for mitotane in Cushing’s disease. Patients using medication monotherapy showed a lower percentage of cortisol normalization compared to use of multiple medical agents (49.4 vs. 65.7%); this was even higher for patients with concurrent or previous radiotherapy (83.6%). Mild side effects were reported in 39.9%, and severe side effects were seen in 15.2% of patients after medical treatment. No meta-analyses were performed for clinical symptom improvement or quality of life due to lack of sufficient data.ConclusionsThis meta-analysis shows that medication induces cortisol normalization effectively in a large percentage of patients. Medical treatment for Cushing’s disease patients is thus a reasonable option in case of a contraindication for surgery, a recurrence, or in patients choosing not to have surgery. When experiencing side effects or no treatment effect, an alternate medical therapy or combination therapy can be considered.
Highlights
Cushing’s syndrome due to endogenous glucocorticoid excess is either adrenocorticotropic hormone (ACTH)dependent or ACTH-independent, both with a variety of underlying causes [1]
Until now no systematic review and meta-analysis has been performed to summarize the effectiveness of all medical agents used in clinical practice
Randomized controlled trials and cohort studies assessing the effectiveness of food and drug administration (FDA)/European Medicines Agency (EMA) approved medical treatment for treatment of Cushing’s syndrome, either de novo or with persistent or recurrent disease, were eligible for inclusion, as well as cabergoline, which has been used for Cushing’s syndrome in multiple investigator initiated clinical trials
Summary
Cushing’s syndrome due to endogenous glucocorticoid excess is either adrenocorticotropic hormone (ACTH)dependent or ACTH-independent, both with a variety of underlying causes [1]. ACTH-independent Cushing’s syndrome is caused by a cortisol-producing adrenal adenoma or carcinoma [1]. Drugs used in medical practice vary per country and underlying cause of Cushing’s syndrome and include ketoconazole, metyrapone, mitotane, cabergoline, pasireotide, and mifepristone [7, 8]. Until now no systematic review and meta-analysis has been performed to summarize the effectiveness of all medical agents used in clinical practice (ketoconazole, metyrapone, mitotane, cabergoline, pasireotide, and mifepristone). The primary aim of the present systematic review and metaanalysis was to evaluate the effectiveness of medical treatment for Cushing’s syndrome in clinical practice. Effectiveness of medical treatment was evaluated regarding cortisol secretion, clinical symptom improvement, and quality of life. The secondary study aim was to compare these medical therapies according to occurrence of side effects
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