Hypothalamic-Pituitary-Adrenal Axis Suppression Related to Itraconazole and Budesonide Association Therapy

Presentation Number: SAT-0779
Date of Presentation: June 21st, 2014

César Esteves1, Celestino Neves*2, Maria João Matos1 and Davide Carvalho1
1Centro Hospitalar São João, Faculty of Medicine, University of Porto, Portugal, 2São João Hospital, Faculty of Medicine, University of Porto, Porto, Portugal

Abstract

Introduction: Cases of iatrogenic Cushing syndrome or adrenal failure are usually the result of the administration of oral glucocorticoids for a long period. Inhaled or topic corticoids aren't usually considered to be responsible for significant abnormalities in the glucocorticoid axis. However, there are exceptions. Aims: To report a case of adrenal failure in a patient treated with itraconazole and inhaled budesonide therapy. Clinical case: Female, 63 years old, under follow-up in a Pulmonology consultation for allergic broncopulmonary aspergillosis. She was treated with itraconazole 400 mg od for 7 months until July 2011 and kept under therapy with budesonide/formoterol 160/4,5 µg / inhalation bid, tiotropium bromide 18 µg/inhalation od and mometasone furoate 50 µg/pulverization od. She was referred to the Endocrinology appointment due to skin hyperpigmentation and weight loss after initiation of therapy with itraconazole, and a morning serum cortisol of 0.05 µg/dL. At the time of the first Endocrinology appointment she complained of subsequent weight gain with centripetal fat deposition and moon face. She had an ACTH below the limit of detection, normal potassium and low aldosterone (0.9 ng/dL). After itraconazole therapy suspension, ACTH increased to 64.1 ng/L, cortisol 9.7 and 18.8 µg/dL before and after the administration of Synacthen, respectively, and aldosterone to 10.3 ng/dL. Due to worsening of aspergillosis, she initiated treatment with itraconazole, with reduction of cortisol levels to 4.0 and 9.3 µg/dL before and after the administration of Synacthen, respectively. Discussion: The present case is representative of itraconazole effects on the pituitary-adrenal axis, in individuals treated with budesonide, which is an inhaled glucocorticoid metabolized by the cytochrome P450 3A4. Mometasone furoate is also a glucocorticoid for nasal pulverization metabolized by the same cytochrome but its systemic absorption is minimal and its contribution in the present case is undetermined. Itraconazole can also induce abnormalities of mineralocorticoid metabolism. Conclusion: Itraconazole is an antifungal agent, considered safe in terms of its effects on the glucocorticoid axis. The occurrence of pituitary-adrenal axis suppression was previously described for the association of itraconazol and budesonide. There are no described cases associated with mometasone furoate. However, it might be considered as it shares the same metabolic pathways as budesonide.

 

Nothing to Disclose: CE, CN, MJM, DC