Efficacy of medical treatment in Cushing's disease: a systematic review

Summary Objective Reported rates of response to medical therapies used in Cushing's disease (CD) vary widely. The aim of this review is to analyse systematically the efficacy of medical therapies for CD and to assess the strength of the supporting evidence. Methods Systematic PubMed searches identified studies of medical treatment in CD. The GRADE criteria were imposed to assess the strength of evidence supporting each medication. Results Fifteen studies were included. Ten studies specifically reported response rates for patients with CD. Pasireotide was the only treatment to be assessed in a randomized trial and was supported by a ‘moderate’ level of evidence. Response rates with pasireotide from three prospective studies were 17–29%. The remaining medications were supported by a ‘low’ or ‘very low’ level of evidence. The highest response rates were reported in small retrospective studies of metyrapone (75%, one study) and mitotane (72%, one study). Response rates were 25–50% for cabergoline (four studies) and 45% for ketoconazole (one study). Among studies that included patients with other forms of Cushing's syndrome, response rates were 53–88% for ketoconazole (three studies), 70% for mitotane (one study), 57% for metyrapone (one study) and 38–60% for mifepristone. Again, all of these medications are supported by a ‘low’ level of evidence. Conclusions There is a paucity of high‐quality studies of medical therapy in CD, with only one medication achieving a ‘moderate’ level of evidence. Caution should be employed when comparing efficacy rates owing to the variability in study design and quality.