Corticosteroid therapy for hearing and balance disorders

Abstract

This review addresses the current status of steroid therapies for hearing and vestibular disorders and how certain misconceptions may be undermining the efficacy in restoring normal ear function, both experimentally and clinically. Specific misconceptions addressed are that steroid therapy is not effective, steroid-responsive hearing loss proves an underlying inflammatory problem in the ear, and steroids only have application to the hearing disorders listed below. Glucocorticoid therapy for hearing and balance disorders has been employed for over 60 years. It is recommended in cases of sudden hearing loss, Meniére's disease, immune-mediated hearing loss, and any vestibular dysfunction suspected of having an inflammatory etiology. The predominant steroids employed today are dexamethasone, prednisone, prednisolone, and methylprednisolone. Despite years of use, little is known of the steroid responsive mechanisms in the ear that are influenced by glucocorticoid therapy. Furthermore, meta-analyses and clinical study reviews occasionally question whether steroids offer any benefit at all. Foremost in the minds of clinicians is the immune suppression and anti-inflammatory functions of steroids because of their efficacy for autoimmune hearing loss. However, glucocorticoids have a strong binding affinity for the mineralocorticoid (aldosterone) and glucocorticoid receptors, both of which are prominent in the ear. Because the auditory and vestibular end organs require tightly regulated endolymph and perilymph fluids, this ion homeostasis role of the mineralocorticoid receptor cannot be overlooked in both normal and pathologic functions of the ear. The function of the glucocorticoid receptor is to provide anti-inflammatory and antiapoptotic signals by mediating survival factors.

Copyright © 2012 Wiley Periodicals, Inc.

Figures

Figure 1

Block diagram illustrating the chain of events for the hypothalamic-pituitary-adrenal (HPA) axis and its actions on target tissues that contain glucocorticoid receptors.

Figure 2

Theory of steroid-responsive hearing loss.

Figure 3

Glycocalyx of the endothelial cells is made up of glycosaminoglycans (GAGs, red) bound to a proteoglycan core (green) that is attached to the endothelial cell (Endo Cell) membrane. Tight junctions (TJ) prevent most circulating factors from entering the inner ear. These structures are naturally removed by circulating inflammatory factors to allow their attachment to the endothelial cell surface. This breaks the tight junctions to permit entry of various serum immune factors to enter the extracapillary space. In the ear, this would break the blood labyrinth barrier, causes loss of the endocochlear potential (EP), and allow serum inflammatory cytokines and immune cells to enter the ear.

Figure 4

Stria vascularis recovery with steroid treatment. The untreated MRL autoimmune mouse shows strial edema and vascular pathology as systemic disease progresses and hearing loss occurs. Note that the stria is free of inflammatory cells. Prednisolone treatment improves hearing and stria appearance. Aldosterone treatment also improves hearing and restores the normal morphology of the stria, similar to a BALB/c mouse that has no disease. Scale = 25µm.

Figure 5

Schematic illustration showing the localization and relative expression of glucocorticoid receptors in the cochlea. The highest expression is found in the spiral ganglion neurons and the least in the outer hair cells.

Figure 6

A highly schematic illustration showing how diurnal cortisol levels (arbitrary values) vary throughout the day for normal young adults (women and men) (Larsson et al., 2009) and for individuals with either depression (Porter et al., 2007), post traumatic stress disorder (PTSD) (Yehuda et al., 2005) or obesity (Farag et al., 2008)). These are only a few examples illustrating how important it is to take into consideration the patient’s endogenous cortisol profile into account before implementing glucocorticoid therapy.