A252/S66: Long-term adrenal insufficiency after treatment with itraconazole and budesonide in CF patients with ABPA: A 5-year follow-up.
M. Skov, T. Pressler
Cystic Fibrosis Center; Copenhagen, Denmark
Aims:
Itraconazole inhibition of CYP3A may interfere with adrenal steroidogenesis and metabolism of budesonide. We have previously found adrenal insufficiency as a side effect ha cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA) treated with itraconazole in combination with budesonide. The present study is a 5 year follow up of adrenal function in these patients.
Methods:
CF patients with ABPA, who developed adrenal insufficiency after combination therapy were included. They were treated with itr aconazole for ABPA (400-600 mg/day) and budesonide as anti inflammatory agent (800-1600 ?g/day). Alter withdrawal of itraconazole and budesonide hydrocortisone substitution therapy (10 mg/m2/day) was started in patients not receiving prednisolone. P- ACTH and stimulated (250 ?g tetracosactid iv) p-cortisol were measured.
Results:
Eleven of 25 (44%) patients had adrenal insufficiency. Median accumulated itraconazole dose was 420 g (3-788 ); median duration of treatment 55 months (1-100). P-ACTH levels normalized within the 1st year after withdrawal. One patient regained adrenal function within the 1st year, one in the 2nd year and two ha the 5th year. Three patients were not re tested due to prednisolone treatment (>5 mg/day). In the remaining 4 patients maximum stimulated p-cortisol levels were 55-213, 174-346,182-373, 178-336 nmol/L after 1, 2, 3 mad 4 years, respectively. Adrenal insufficiency was unrelated to dose and duration of treatment.
Conclusions:
Within the 5 year period 1/3 of the patients did not recover, 1/3 slowly regained adrenal function and 1/3 stayed on prednisolone treatment to control ABPA. Adrenal suppression, irrespective of the duration, may last for years. Monitoring of adrenal function during and after withdrawal of treatment is crucial.