Adrenal Suppression in EoE Treated With Budesonide?

Abstract

See “Adrenal Suppression in Children Treated With Oral Viscous Budesonide for Eosinophilic Esophagitis” by Panagiotopoulos et al on page 190. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Panagiotopoulos et al (1) report on the results of a quality assurance (QA) project conducted in children with eosinophilic esophagitis (EoE) treated with budesonide. They disclose evidence that adrenal suppression may result from administering therapeutic doses of budesonide for relatively short (<3 months and longer) time periods. During the last decade, the number of children being diagnosed as having EoE has greatly increased. A full understanding of the implications of the diagnosis is lacking. Therefore, an appreciation of the risks and benefits of any 1 therapy, such as glucocorticoids (GCs), is also unclear. That the study was undertaken as a QA project raises issues both of its scientific value and its place in a scientific peer-reviewed journal. Readers should take note that this is not a rigorously designed prospective study of the type all editors like to publish. It does however have a place as a “hypothesis generating” or (as described) a “pilot” study. The authors have felt appropriately compelled to bring to our attention the potential risks inherent in a treatment regarded as relatively benign. Budesonide treats the symptoms of EoE effectively. It is a GC, but because it is rapidly metabolized in the liver, it is considered less likely to result in adverse effects associated with the systemic use of other GCs. It has never been suggested that budesonide is completely safe, but it is possible that clinicians have become too comfortable with its safety profile. The introduction of GC as therapy for various clinical conditions started in the 1950s (2). Currently, they are used as physiologic replacement in adrenal insufficiency and pharmacologic treatment in a variety of conditions including rheumatologic diseases, nephrotic syndrome, asthma, inflammatory bowel diseases, and EoE. As a general rule, treatment with GC requires close monitoring for both undertreatment and overtreatment. Undertreatment can result in adrenal insufficiency, and overtreatment may lead to growth suppression, iatrogenic Cushing syndrome, and hypothalamic-pituitary-adrenal (HPA) axis suppression/secondary adrenal insufficiency. HPA axis suppression can occur with the use of GC therapy of >2 weeks duration, which exceeds physiological doses (the normal endogenous cortisol secretory rate is 6–8 mg · m−2 · day−1 in children and adults (3,4)). HPA axis suppression has been reported in prolonged systemic, topical, and intralesional GC therapy (2,5). The low-dose 1-μg adrenocorticotropic hormone test used by the authors is more sensitive than the standard-dose (250 μg) test (2,6–8); thus, if the findings reported are confirmed, then the screening and testing for secondary adrenal insufficiency in patients being treated with budesonide for an extended time period is warranted. Also, stringent guidelines for the use of budesonide might be considered. The authors did not find significant association with the treatment duration, dose, or concomitant use of inhaled/nasal corticosteroids. This should be interpreted with caution because of the small sample size and study design (or perhaps lack of design.) Other risk factors for adrenal suppression may include efficiency of gastrointestinal absorption related to diet, gastric acidity, bowel transit time, and interindividual sensitivity to GC related to genetic factors (9). A prospective study measuring adrenal suppression in EoE patients matched for disease extent and randomized to receive either budesonide or a nonsteroid treatment is warranted to determine the significance of the findings disclosed. The early symptoms of secondary adrenal insufficiency can be too subtle to note, but until the true incidence and extent of adrenal suppression is known, it is worthy of consideration to provide hydrocortisone supplementation in times of stress (such as major surgery) to any patient who has been treated with budesonide for 3 months in the last year.