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This version published online on March 31, 2005
Endocrinology, doi:10.1210/en.2005-0080
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Submitted on January 19, 2005
Accepted on March 21, 2005

Evidence for Ototopical Glucocorticoid-induced Decrease in Hypothalamic-Pituitary-Adrenal Axis Response and Liver Function

GETU ABRAHAM*, JUTTA GOTTSCHALK, and FRITZ RUPERT UNGEMACH

Leipzig University, Institute of Pharmacology, Pharmacy and Toxicology (G.A., F.R.U.), Institute of Physiological Chemistry (J.G.), An den Tierkliniken 15, 04103 Leipzig, Germany

* To whom correspondence should be addressed. E-mail: gabraham{at}rz.uni-leipzig.de.

To help clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis activity (HPA) and altered hepatic metabolism, one commercially available dexamethasone containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function.

Ten beagle-dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 days in a single-blind and placebo-controlled study. Resting cortisol concentrations were assessed before, during and after treatment using RIA system. The adrenal function and HPA axis feedback sensitivity was measured by a standard-dose (250 µg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function and blood cell counts.

Ototopical dexamethasone treatment induced a marked suppression (to about 100%) in resting plasma cortisol concentrations below placebo (P < 0.0001) within the first 11 days, and remained reduced during the whole treatment period on day 19. As well, ACTH stimulation test resulted in a markedly reduced rise of plasma cortisol concentrations (P = 0.0004). Concomitantly, a significant increase in serum activities of alkaline phosphatase (ALP), {gamma}-glutamyl transferase (GGT), alanine transaminase (ALAT) and aspartate transaminase (ASAT) was detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. While cortisol levels and hematological parameters returned to baseline 7 days after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the audiotory canal, to suppress the HPA axis function as well as to alter metabolic and hematopoeitic profiles. Thus, long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.


Key words: ototopical glucocorticoids • cortisol • HPA axis • liver function




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