High Prevalence of Hearing Impairment in Primary Congenital Hypothyroidism

Abstract

<b><i>Background:</i></b> An association between hearing impairment (HI) and congenital hypothyroidism (CH) has been reported previously. However, in general, studies were retrospective and had small sample sizes, and the results were variable and inconclusive. The aim of our study was to assess the prevalence of HI among patients with CH and to examine factors potentially predictive of HI including severity of CH, etiology of CH, and timing of treatment initiation. <b><i>Methods:</i></b> Audiometry was undertaken prospectively in 66 patients aged 3–21 years diagnosed with primary CH and 49 healthy matched controls. All patients with HI underwent examination by an otolaryngologist, and in patients with sensorineural loss, brainstem evoked response audiometry was performed. A next-generation sequencing (NGS) panel for genes involved in deafness was performed in patients with sensorineural HI to exclude additional genetic etiologies. <b><i>Results:</i></b> HI was found in 19 patients (28.7%). Among them, 5 (7.6%) had moderate to severe bilateral sensorineural impairment and 14 (21.2%) had mild conductive HI. Conductive HI was bilateral in 5 of these patients (36%). None of the controls had HI. No specific etiology was found in patients with HI, and no differences were identified in age at diagnosis, age at initiation of levothyroxine (LT<sub>4</sub>) therapy, gender, or ethnicity between patients with and without HI. A nonsignificant trend toward lower mean screening TT<sub>4</sub> levels was found in patients with HI (compared to those without HI) (3.42 vs. 5.34 μg/dL, <i>p</i> = 0.095). No pathogenic variants in genes attributed to HI were identified by NGS in the 5 patients with sensorineural deafness, indicating that HI in these patients was likely attributable to CH rather than other genetic etiologies. <b><i>Conclusions:</i></b> Our findings indicate a high prevalence of HI among patients with CH, predominantly of the conductive type. HI was not associated with the etiology of CH or with delayed initiation of LT<sub>4</sub> therapy. Audiometry is recommended for children diagnosed with CH and repeat monitoring may be warranted to identify acquired HI and to prevent long-term sequelae of undiagnosed deafness.

Long-Term Outcome of Patients with TPO Mutations

“…Four patients had sensorineural hearing impairment. A high rate of hearing impairment in CH has been shown recently by our group [24]. Furthermore, TPO mutations have been reported to be associated with sensorineural deafness in humans [25] as well as in animal models [26], indicating that the TPO enzyme itself may have a role in the development of the auditory system.…”

Sensorineural hearing loss in a child with congenital hypothyroidism receiving thyroid hormone replacement therapy

“…2,14 This further highlight the importance of timely treatment in children with congenital hypothyroidism, especially considering that the severity of congenital hypothyroidism and the child's age at treatment initiation is directly associated with the degree of hearing loss. 15 In our presented case, the patient first referred to us at the age of 6 months where growth and developmental disorders had occurred. As the patient's auditory organs had been damaged, it became difficult to rehabilitate the patient's hearing ability.…”

Dysfunction of the Auditory System in Children With Hypothyroidism: A Systematic Review and Meta-Analysis

“…Additionally, some studies detailed subtypes of CH including athyreosis, dysgenesis, ectopic thyroid, dyshormonogenesis, and transient CH. While some studies reported no association between hearing impairment and CH etiology (Vanderschueren-Lodeweyckx et al 1983;Almagor et al 2020), other studies observed more severe HL in their children with athyreosis compared to ectopic thyroid (Lichtenberger-Geslin et al 2013;Bruno et al 2015). Bruno et al (2015) noted an association between children with severe CH (defined by CH etiology including athyreosis, TSH levels, and age at bone maturation delay) and greater degrees of HL as assessed by PTA.…”

“…Following widespread screening, intellectual disability due to CH decreased significantly; however, the effect of early screening and treatment on hearing outcomes in children has been less dramatic. Reports of HL prevalence range from 20% to 47% (Vanderschueren-Lodeweyckx et al 1983; Rovet et al 1996; Almagor et al 2020) in cohort studies and the effect of LT4 therapy on hearing improvement is not well-established based on the few longitudinal studies that have followed children into adolescence (Léger et al 2011; Lichtenberger-Geslin et al 2013). Even in older children with CH and normal-hearing thresholds, subclinical hearing disorders could be present.…”