Discussion

The major finding of this study was that the serum iron level, but not haemoglobin level, was significantly higher in the complete recovery than in the non-complete recovery group, despite the significant correlation between the serum iron and haemoglobin levels. This result indicates that the serum iron level might be a novel independent biomarker for predicting the prognosis of patients with idiopathic sudden SNHL. Moreover, we demonstrated that higher initial hearing threshold was associated with a poor prognosis in idiopathic sudden SNHL, which is consistent with the findings of previous studies.^{Reference Kuhn, Heman-Ackah, Shaikh and Roehm11}

Currently, a treatment strategy for idiopathic sudden SNHL has not been established because the aetiology of idiopathic sudden SNHL is still not fully understood. Blood circulatory disorders, hypoxia, oxidative stress and elevated intracellular levels of reactive oxygen species have been considered to be one of the crucial causes of idiopathic sudden SNHL.^{Reference Hsu, Hu, Chiu, Lee and Huang12} Because the cochlear tissues are supplied with oxygen and nutrients by the labyrinthine artery without collateral circulation, obstruction of the blood supply by thrombosis may cause cochlear ischemic damage, resulting in the symptoms of idiopathic sudden SNHL. Furthermore, oxidative stress was found to play a major role in cochlear damage in an animal model of hearing loss.^{Reference Kurioka, Matsunobu, Satoh, Niwa and Shiotani13} Considering the above, various empirical treatments, such as vasodilators, anticoagulants or antioxidant agents have been applied for idiopathic sudden SNHL to improve blood circulation and oxygen supply and reduce oxidative stress. Accurately predicting the prognosis is also extremely important in clinical practice to determine whether additional intensive treatment, such as intratympanic steroid injection, should be applied. However, there are still no treatments or prognostic factors that show unequivocal evidence of efficacy for patients with idiopathic sudden SNHL.

Iron is a critical and indispensable element for maintaining the metabolic requirements of neuronal tissues. Recently, it was reported to have a central role in the association between neurodegeneration and oxidative stress in neurodegenerative diseases.^{Reference Belaidi and Bush14} The auditory system is also affected by iron metabolism.^{Reference Castiglione, Ciorba, Aimoni, Orioli, Zeri and Vigliano15} Hearing loss caused by iron deficiency may gradually progress, and iron deficiency may be associated with the pathogenesis of idiopathic sudden SNHL.^{Reference Brissot, Ropert, Le Lan and Loreal16}

Iron deficiency impairs energy production and, consequently, myelin production. Damage to the myelin surrounding the auditory nerve impairs the conduction velocity, resulting in auditory impairment. It has been reported that iron supplementation contributed to maintaining the integrity of the blood-labyrinth barrier and homeostasis in the cochlea.^{Reference Liu, Zheng, Wu, Shen, Jing and Yu17} Accordingly, iron homeostasis could be potentially associated with idiopathic sudden SNHL and be a central pathway involved in its pathophysiology.

Moreover, iron deficiency impairs erythropoiesis, resulting in iron-deficiency anaemia and leading to impaired capacity for oxygen supply. Iron-deficiency anaemia has also been demonstrated to be significantly associated with age-related hearing loss.^{Reference Schieffer, Chuang, Connor, Pawelczyk and Sekhar8} In contrast, iron may exert not only neuroprotective but also neurotoxic effects, such as acceleration of reactive oxygen species production, resulting in apoptotic cell death in the organ of Corti.^{Reference Henderson, Bielefeld, Harris and Hu5} These findings indicated that the prognosis of idiopathic sudden SNHL may potentially be positively or negatively influenced by the serum iron level.

Our findings that decreased serum iron levels were associated with poor prognosis in idiopathic sudden SNHL indicate that iron plays important roles in the recovery of idiopathic sudden SNHL mediated by promotion of vascular oxygen supply and mitochondrial respiration in the inner ear. Although none of the patients in our study had serum iron overload (more than 180 μg/dl), serum iron overload might lead to acceleration of reactive oxygen species production, resulting in poor outcome of idiopathic sudden SNHL.

Regarding iron status, we only measured haematological data, including red blood cell count, haemoglobin, serum iron level, haematocrit and mean corpuscular volume. Although these variables are not optimal for reflecting the iron status of patients with idiopathic sudden SNHL, the findings of this study have some clinical implications that are significant in terms of the understanding and management of patients with idiopathic sudden SNHL. Our results might indicate that patients with idiopathic sudden SNHL with low levels of serum iron might preferably receive comprehensive and intensive treatment in order to prevent poor results. Although the role of iron in idiopathic sudden SNHL is not well known, its effects need to be considered in the management of idiopathic sudden SNHL in clinical practice.

This study has some limitations. First, it was performed at a single hospital, and the sample size was relatively small. Second, ferritin, the major iron storage protein accumulating great amounts of iron, was not included in the haematological variables measured in this study. Therefore, further studies with larger populations that include the ferritin level are warranted to determine the effects of the iron metabolism on the prognosis of idiopathic sudden SNHL.