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Evidence for ototopical glucocorticoid-induced decrease in hypothalamic-pituitary-adrenal axis response and liver
Getu Abraham1, Jutta Gottschalk, Fritz Rupert Ungemach
1Leipzig University, Institute of Pharmacology, Pharmacy, and Toxicology, An den Tierkliniken 15, D-04103 Leipzig, Germany. gabraham@rz.uni-leipzig.de
Endocrinology
|April 2, 2005
Summary
Ototopical dexamethasone treatment significantly suppresses the hypothalamic-pituitary-adrenal (HPA) axis and alters liver enzymes and blood cell counts in dogs. Systemic effects should be considered with long-term use.
Area of Science:
- Veterinary Pharmacology
- Endocrinology
- Toxicology
Background:
- Limited knowledge exists regarding the systemic effects of ototopical glucocorticoid treatments on the hypothalamic-pituitary-adrenal (HPA) axis and hepatic function.
- Ototopical glucocorticoids are commonly used for treating ear conditions, necessitating an understanding of their potential systemic absorption and impact.
Purpose of the Study:
- To investigate the impact of a dexamethasone-containing ointment applied to the ear canal on HPA axis activity.
- To evaluate alterations in hepatic metabolism and hemopoietic profiles following ototopical dexamethasone administration.
Main Methods:
- A single-blind, placebo-controlled study involving ten beagle dogs treated with dexamethasone ointment (0.6 mg/ear/day) for 21 days.
- Assessment of resting cortisol levels, adrenal function via ACTH stimulation tests, serum biochemical parameters (including liver enzymes), and hematological profiles.
- Measurements were taken before, during, and after the treatment period.
Main Results:
- Ototopical dexamethasone caused significant suppression of resting plasma cortisol concentrations and a blunted cortisol response to ACTH stimulation, indicating HPA axis impairment.
- Elevated serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were observed.
- Changes in leukocyte counts included decreased eosinophils and lymphocytes, with increased neutrophils. Most hematological parameters normalized post-treatment, but liver enzymes remained elevated.
Conclusions:
- Dexamethasone applied ototopically is absorbed sufficiently to suppress HPA axis function and alter metabolic and hemopoietic parameters.
- Long-term ototopical glucocorticoid therapy requires consideration of potential systemic HPA suppression, especially concerning stress.
- Elevated serum enzyme activities post-treatment may not necessarily indicate liver damage (hepathopathy) but rather reflect metabolic changes.