ECE2016 Eposter Presentations Pituitary - Clinical (83 abstracts)
Ketoconazole in Cushing’s disease management
Sofia Oliveira 1, , João Neves 1, , Celestino Neves 1, , Sandra Belo 1, , Paula Freitas 1, , Duarte Pignatelli 1, , José Castedo 1, , Eduardo Vinha 1, , Ana Oliveira 1, & Davide Carvalho 1,
1Department of Endocrinology, Diabetes and Metabolism of Centro Hospitalar de São João, Porto, Portugal; 2Faculty of Medicine, University of Porto, Porto, Portugal; 3Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal.
Background: Transphenoidal surgery is still the best initial therapy for Cushing’s disease (CD), with a high probability of cure and few risks or complications. However, pharmacotherapy has a role as primary or adjunctive therapy: when surgery is delayed, in case of postoperative persistence or recurrence of hypercortisolism, or while waiting for radiotherapy effectiveness. Ketoconazole, a steroidogenesis inhibitor, is nowadays the main drug used to CD control by reducing cortisol levels, with potent antisecretory efficacy in majority of cases, and relatively rare major side effects (anaphylaxis and fulminant hepatitis), but its use remains controversial.
Objective: The present study aims to assess the efficacy and tolerance of ketoconazole in CD and evaluate the benefit/risk balance.
Patients and methods: We reviewed ten present cases of CD treated with ketoconazole in our center, with a mean follow-up of 16±15.3 months (0.25–40). Clinical assessment included age, gender distribution, BMI, blood pressure, levels of serum cortisol and ACTH, urinary free cortisol (UFC), hepatic function, lipid profile, glucose and HbA1c levels, hypokalemia and GI tolerance.
Results: The mean age of the participants was 43.7±13.01 years, 80% females, with a BMI of 29±6.2 kg/m2. Eight patients (80%) are receiving the drug for 3–40 months, with a mean final dose of 500±270.8 mg. One patient suspended treatment after 1week due to GI intolerance and another one after 13 months due to an infectious intercurrence. At the last follow-up, 60% of patients had normal UFC levels, 50% had at least a 50% decrease and 10% had unchanged UFC levels. Increase in liver enzymes was generally mild and reversible (90%), with 1 (10%) case of major increase. No fatal hepatitis was observed.
Conclusion: Ketoconazole is a safe and efficacious drug in CD, but has the potential hepatotoxicity that requires careful selection of patients and subsequent clinical and biochemical monitoring.
Keywords: Cushing’s disease, ketoconazole, steroidogenesis inhibitors, hypercortisolism
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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