Not much was known about the impact of the major β-thalassemia disease and the toxicity of DFO therapy on hearing organ in southern Iran. We found an incidence of only 3.5% SNHL in a large population of patients.
In fact conflicting reports and great discrepancy between the incidences of hearing impairment has a long and rich history. It has appeared in the literature during the past 30 years. The first experience of de Virgiliis group in 1975 when they reported high-tone sensorineural hearing loss in 14 of 20 patients with beta-thalassaemia major[
10], and later in 1979 when the same group reported moderate unilateral or bilateral high-tone sensorineural deafness in 43 of 75 patients, however, all patients were receiving chelation therapy with DFO, but de Virgiliis et al did not consider this to be causative[
11]. Several authors have studied the ototoxicity of DFO, Some studies have reported frequencies of SNHL between 7.4% and 33%[
2,
12].
Despite small sample size in most of the studies, no statistically significant differences were found between the affected and unaffected groups with respect to age, ferritin levels or lengths of time that they had received and dose of DFO, peak DFO dose and iron overload[
2,
4,
12–
14].
The therapeutic index suggested by Porter et al[
15] also was not helpful in predicting risk for ototoxicity[
2]. The prevalence of hearing loss in thalassaemia patients in other studies were 25% in Olivieri et al (n=89), 33% in Barratt et al. (n=27)[
14], 24% in Porter et al. (n= 37)[
15], 15.5% in Argiolu et al (n=308)[
13], 27% in Kontzolglulou et al (n=88)[
14], 29% in Styles et al (n=28)[
2] and 3.4% in our study.
In a recent study by Shamsian et al. they found the incidence of 7.4% SNHL in 67 patients suffered from major β-thalassemia who treated with deferoxamine. They defined hearing loss as a hearing threshold more than 15 dB. Although they did not report what frequencies involved specifically, the researchers detected there was no association between serum ferritin level or DFO dosage and hearing loss[
16].
Although there is discrepancy in the rates between our study and foregoing reports, the difference may be as a result of our definition for hearing loss, ototoxicity, and exclusion criteria.
We reviewed the audiograms of Barratt et al study[
12]; three of those patients, had a history of recurrent acute ear infections. In three patients whose hearing loss was only above 6 kHz, bone conduction could not be assessed by the authors. We also reviewed the findings of Porter et al[
15] Survey, from all 9 cases, in 5 patients hearing loss was only in one frequency above 6 kHz. Actually in Styles and Vichinsky's[
2] study we see that of nine patients with abnormal audiograms in 5 of them one frequency was abnormal.
In a research by Karimi et al, 128 patients receiving subcutaneous DFO in doses from 21 to 39 mg/kg/day were studied in 2002. Patients had received their total weekly dose of DFO according to two different methods. The first group had received it on an every other day basis and the second group had received it on 6 days a week. Of the patients in the first group 44.7% had hearing loss in the right ear and 41.8% in the left ear only at 8000 Hz frequency, compared to the second group, 27.8 and 23%, respectively. A significant correlation was found between the dose of drug given at each episode of DFO therapy and hearing loss at the frequency of 8,000 Hz. They concluded that DFO ototoxicity is determined not only by the total amount of the drug given, but also by its maximal plasma concentration[
17]. However they reported higher frequency of SNHL than other authors, they considered that hearing loss was significant only at one (8000 Hz) frequency.
A retrospective controlled study by Masala et[
18] al showed a 12% rate of SNHL in patients with thalassemia treated with DFO. The control group of normal patients showed a 10% rate of SNHL. They found no significant difference between thalassemic patients and controls, and concluded that there were inadequate data for DFO otoxicity. Similar findings were reported by Cohen et al who found that 49 out of 52 patients treated with DFO, had no auditory or visual abnormalities[
19]. The lack of ototoxic side effects at lower doses can be considered in good harmony with clinical reports of the low incidence of toxic side effects of DFO[
5,
20–
23]. In a recent national health survey by Agrawal et al, on the prevalence of hearing loss among US adults, they found in the youngest age group (20–29 years), 8.5% showed high -frequency hearing loss, and the prevalence seems to be growing among this age group[
24].
Other authors have agreed with this opinion that the DFO dose generally used (<50 mg kg/ day) is not ototoxic. They report a frequency of hearing loss similar to that in the normal population. Ambrosetti et al[
4] in a review of 38 adult patients with thalassemia major support this view since in their patients SNHL was related to neither therapeutic index, nor serum ferritin levels. Furthermore, the percentage of patients with SNHL is similar to that in the normal population of the same age (15–35%). Ambrosetti et al. data suggest that no difference exists between thalassemic patients and non-thalassemic population, and it is adequate to conclude that DFO is not ototoxic[
4].
