Year : 2016 | Volume
: 13 | Issue : 2 | Page : 67--70
Hearing impairment in children with permanent congenital hypothyroidism: Data from Northwest India
Devi Dayal1, Nirmal Hansdak2, Dharam Vir3, Atul Gupta4, Jaimanti Bakshi3,
1 Department of Pediatrics, Advanced Pediatric Center, Pediatric Endocrinology and Diabetes Unit, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Otolaryngology and Head and Neck Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
4 Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India
Dr. Devi Dayal
Department of Pediatrics, Pediatric Endocrinology and Diabetes Unit, Advanced Pediatric Center, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
Background: There is an increased risk of hearing impairment in permanent congenital hypothyroidism (CH). Only a few studies have explored the prevalence of hearing impairment in CH and their results vary widely. There is no data on hearing impairment in Indian children with CH. Setting and Design: Pediatric Endocrinology Clinic of a large tertiary care hospital located in Northwest India. Cross sectional study. Materials and Methods: Hearing evaluation of 77 children diagnosed with permanent CH was performed with a battery of tools that included Middle ear analysis, Pure Tone Audiometry (PTA), Behavioral Observation Audiometry (BOA) and Oto Acoustic Emissions (OAE). The choice of assessment tool was based on patient's age. Results: The mean age at diagnosis and at inclusion into the study was 3.0±2.7 years and 5.2±3.3 years respectively. The majority (63, 82%) of patients had symptoms suggestive of hypothyroidism; none complained of hearing loss. The etiological diagnosis was thyroid agenesis in 55 (71.4%), ectopia in 5 (6.5%), dyshormonogenesis in 9 (11.7%) and hypothyroidism with eutopic gland in 8 (10.3%) patients. Middle ear analysis, PTA, BOA and OAE was done in 48, 44, 43 and 53 patients respectively. Sensorineural hearing loss was detected in 1 out of 77 (1.2%) patients while conductive hearing loss was found in 5 (6.5%) patients. Conclusion: Hearing loss was present in a small proportion of patients with permanent CH. Further larger studies are required to determine the exact prevalence of hearing impairment in Indian children with permanent CH.
|How to cite this article:|
Dayal D, Hansdak N, Vir D, Gupta A, Bakshi J. Hearing impairment in children with permanent congenital hypothyroidism: Data from Northwest India.Thyroid Res Pract 2016;13:67-70
|How to cite this URL:|
Dayal D, Hansdak N, Vir D, Gupta A, Bakshi J. Hearing impairment in children with permanent congenital hypothyroidism: Data from Northwest India. Thyroid Res Pract [serial online] 2016 [cited 2022 May 29 ];13:67-70
Available from: https://www.thetrp.net/text.asp?2016/13/2/67/183278
Congenital hypothyroidism (CH) is the most common endocrine disorder in children with an estimated prevalence of 1:2000–1:4000 live births. The thyroid hormones are essential for the development of the inner as well as the middle ear., Genetic studies in animal models indicate a relationship between thyroid hormones and auditory system development., The deletions of gene for dual oxidase 2 which is required for iodide oxidation in thyroid gland result in anatomical changes of the internal ear and low hearing threshold. Similarly, mutations of Pax 8 gene in mice cause thyroid agenesis and hearing impairment. The risk of hearing impairment is thus increased in CH. The association between CH and hearing impairment has indeed been recognized for a long time.,
The health burden of sensorineural hearing loss (SNHL) is significant worldwide (2–4/1000 children in the developed countries and 1–8/1000 babies in less developed countries)., CH has been identified as one of the several risk factors for SNHL in studies on prevalence of hearing loss. However, the prevalence of hearing loss in patients with CH has been explored in only a few studies and the results are conflicting. In a study from Iran before the beginning of neonatal screening for hypothyroidism, hearing impairment was noted in 50% of patients with CH; the hearing loss was severe and profound in CH due to dyshormonogenesis (DH) and mild or moderate in patients with thyroid agenesis. Others have detected audiological abnormalities ranging between 20% and 25% of children with CH diagnosed after neonatal screening., Recent data from Iran suggest a low prevalence (3.2%) of hearing loss in patients with CH. There is no data on hearing impairment in CH from India.
Children with even mild form of hearing loss may suffer from delayed speech and various other developmental and learning impairments. Many of these overt or subtle abnormalities are amenable to prevention with early detection and treatment of hearing loss. The health burden of CH related hearing impairment and its consequences may be high in India in view of the recent reports of an alarmingly high incidence of CH (1:914–1:1985)., We thus aimed to study the prevalence of hearing impairment in children with permanent CH and its relation age at starting thyroxine (T4) therapy.
Materials and Methods
Children aged 6 months to 12 years diagnosed as permanent CH and on replacement therapy were recruited from pediatric endocrinology clinic between July 2012 and December 2013 and underwent audiological evaluation in the Speech and Hearing Unit of the Department of Otolaryngology of our hospital. The diagnosis of hypothyroidism was based on low serum total T4 and elevated serum thyroid stimulating hormone levels according to reference ranges. Etiological diagnosis was based on the findings of technetium- 99m pertechnetate thyroid scintiscan and thyroid ultrasonography performed routinely in our hospital at the time of initial evaluation of CH. Perchlorate discharge test was done in selected cases. Those having subclinical hypothyroidism, transient hypothyroidism, history of familial hearing loss, dysmorphism, especially craniofacial anomalies, past history of significant neurological insult (bacterial meningitis, head trauma, mental retardation), otitis media or any other ear disease, significant neonatal problems such as very low birth weight, hyperbilirubinemia, mechanical ventilation, use of ototoxic medications were excluded. Autoimmune thyroid disease was excluded by routinely performing antithyroid peroxidase antibodies in all patients. Children who fulfilled the criteria were enrolled into the study after obtaining written informed consent from the parents/caretakers and assent from the child if above 8 years of age. The study was approved by the Institute's Ethics Committee.
The clinical and biochemical data were recorded into a prestructured proforma. A detailed otorhinolaryngological examination was done to exclude conditions listed in the exclusion criteria. The audiological investigations were done on all the patients by the same audiologist and on same instruments. The choice of hearing assessment tool was based on the patient's age and the ability to cooperate and included the following:
Middle ear analysis
After an otoscopic examination to ensure that there was no wax or perforation, the test was performed by inserting the probe of Immittance Meter (MAICO MI 34, MAICO Diagnostics, Berlin, Germany) into the ear canal. A tympanogram was obtained based on the pressure variance at 226 Hz.
Pure tone audiometry
Pure-tone hearing thresholds were estimated in the frequency range of 250 Hz to 8 kHz using Madsen Orbiter 922 Clinical Audiometer Version II (GN Otometrics, Taastrup, Denmark) which was calibrated according to ANSI standards. Air conduction and bone conduction pure tone threshold curves were obtained for each ear separately. High-frequency audiometry measuring thresholds at 10, 12, and 16 kHz was performed with the same audiometer. The pure tone average thresholds at 500, 1000, and 2000 Hz were also recorded for each ear. Speech recognition thresholds test was done to determine the faintest level at which a person could hear and repeat words presented at a comfortable intensity (e.g., 30–40 dB above the pure tone audiometry [PTA] of 500, 1000, and 2000 Hz). Speech discrimination score was calculated as the percentage of correctly repeated words after presenting 25 phonetically balanced monosyllables to the test ear at an intensity of 40–50 decibel above the average air conduction threshold for 500, 1000, and 2000 Hz, with the nontest ear masked adequately.
Behavioral observation audiometry
Behavioral responses were recorded to a variety of nonverbal stimuli for children aged <3 years and those not cooperative for PTA. The behavior was analyzed by observing consistent age-appropriate responses.
Transient evoked otoacoustic emissions (TrOAE) and distortion product OAE (DPOAE) were performed on SmartOAE and SmartTrOAE instruments (Intelligent Hearing Systems, Miami, USA), respectively. Individuals with abnormal results on behavioral observation audiometry (BOA) and OAE testing were further considered for brain stem evoked response audiometry.
All data were coded and entered in SPSS for Windows (Version 20.0; IBM Corp., Armonk, NY, USA) for analysis. Descriptive statistics was reported as mean and standard deviation while the qualitative variables were recorded in proportions. Associations were evaluated using Pearson correlation test, Chi-square test, and Fisher's exact test. Multiple regression analysis was used to access the relationship of hearing loss to factors such as age at diagnosis and dose of T4. A P < 0.05 was considered statistically significant.
The study population consisted of 77 children; 45 (58.4%) were girls. Their mean age at inclusion into the study was 5.2 ± 3.3 years; majority (36, 47%) were <4 years of age. The interval between diagnosis of CH and the date of enrolment into the study was <1, 1–3 years and >3 years in 20 (26%), 28 (36.4%) and 29 (37.7%) patients, respectively. The mean age at diagnosis was 3.0 ± 2.7 years. The presenting features included constipation in 31 (40.3%), developmental delay in 14 (18%), lethargicness in 12 (15.6%), prolonged neonatal jaundice in 11 (14.3%), growth retardation in 10 (13%), and attention deficit in 1 (1.3%). Fourteen (18%) had nonspecific symptoms. None of the patients complained of hearing loss. The etiology of CH based on the results of combined scanning and PDT was thyroid agenesis in 55 (71.4%), ectopia in 5 (6.5%), DH in 9 (11.7%), and hypothyroidism with eutopic gland in 8 (10.3%). The dose of T4 was <37.5 mcg, 50–75 mcg, and 87.5–200 mcg in 29 (37.7%), 32 (41.6%), and 16 (20.8%) patients, respectively.
Impedance audiometry was performed in 48 patients. Forty-three (89.5%) patients had normal type A tympanogram, and 5 (10.5%) had type B tympanogram suggestive of conductive pathology of the left ears. On the right side, 46 (95.8%) patients showed type A tympanogram and 2 (4.2%) had type B tympanogram.
PTA was done in 44 patients in both the ears and showed normal results. There was no relation between age, age at diagnosis, and dose of T4 and frequencies in both the ears.
All the 43 patients who underwent BOA showed normal response in the right ear. In the left ear, response was absent in 1 patient suggestive of mild SNHL.
Fifty-three patients who underwent TrOAE and DPOAE showed normal results. There was no correlation between ages and test frequencies in both the ears, except a negative correlation between age at diagnosis and 1 kHz frequency (r2= −0.398, P = 0.00) on TrOAE of the left ear, and between initial thyroid hormone levels and 1.5 kHz frequency (r2= −0.279, P = 0.05) of the right ear. On DPOAE, an inverse correlation (r2= −0.386, P = 0.05) was seen between age and frequency of 4 kHz in the left ear only. On the right side, no correlation was seen between age, age at diagnosis, and dose of T4 and frequencies ranging from 0.5 to 6 kHz.
Based on the results of all the hearing assessment tests, SNHL was detected in 1 out of 77 (1.2%) patients while conductive hearing loss was found in 5 (6.5%) (unilateral in 3) patients.
The majority of our patients showed normal hearing and the prevalence of 1.2% are probably the lowest reported so far. A previous study from Iran estimated a prevalence of 3.2% in CH patients diagnosed by newborn screening and initiated on early treatment. In all other studies, the prevalence of hearing impairment ranged between 20% and 50%.,, However, François et al. documented normal hearing in all the 42 children of a cohort of CH. The differences in results can partly be attributed to small sample sizes. The number of patients assessed for hearing impairment ranged between 32 and 75 in the previous studies.,,, Other factors that may contribute to differences in prevalence are the methods of hearing assessment, age of hearing examination, or differences in genetic factors in different patient populations. Genetic component in CH is indicated by an increased occurrence in down syndrome, advanced maternal age, and increased occurrence in families. The only patient who was detected to have hearing impairment in our study had DH similar to previous observations. The higher risk of hearing impairment in DH is probably due to the underlying genetic factors.
The effect of treatment or the dose of T4 did not seem to have any relationship with hearing impairment in our patients. Treatment with T4 was shown to improve the minor abnormalities of hearing in a previous study. The improvement was attributed to a better recruitment of neuronal pool of the generators of the auditory brainstem response waves in the brainstem and thalamocortical projections of the auditory pathways which are adversely affected in the hypothyroid state. However, even with early treatment, specific auditory brainstem evoked potential abnormalities were found in 25% of patients in another study. The conductive hearing loss observed in some of our patients is probably because of common occurrence of otitis media in this age group in our set up.
Hearing loss was present in a small proportion of patients with permanent CH and should be detected by a battery of modern hearing evaluation tests. There is no relationship of hearing impairment in these children with the age at diagnosis and the dose of T4 that they receive. Further larger studies are required to map the exact burden of hearing impairment in Indian children with CH.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Dayal D, Prasad R. Congenital hypothyroidism: Current perspectives. Res Rep Endocr Disord 2015;5:91-102.|
|2||Knipper M, Zinn C, Maier H, Praetorius M, Rohbock K, Köpschall I, et al. Thyroid hormone deficiency before the onset of hearing causes irreversible damage to peripheral and central auditory systems. J Neurophysiol 2000;83:3101-12.|
|3||Cordas EA, Ng L, Hernandez A, Kaneshige M, Cheng SY, Forrest D. Thyroid hormone receptors control developmental maturation of the middle ear and the size of the ossicular bones. Endocrinology 2012;153:1548-60.|
|4||Weber G, Rabbiosi S, Zamproni I, Fugazzola L. Genetic defects of hydrogen peroxide generation in the thyroid gland. J Endocrinol Invest 2013;36:261-6.|
|5||Bouchard M, de Caprona D, Busslinger M, Xu P, Fritzsch B. Pax 2 and Pax 8 cooperate in mouse inner ear morphogenesis and innervation. BMC Dev Biol 2010;10:89.|
|6||Refetoff S, DeWind LT, DeGroot LJ. Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: Possible target organ refractoriness to thyroid hormone. J Clin Endocrinol Metab 1967;27:279-94.|
|7||DeLong GR, Stanbury JB, Fierro-Benitez R. Neurological signs in congenital iodine-deficiency disorder (endemic cretinism). Dev Med Child Neurol 1985;27:317-24.|
|8||Smith RJ, Bale JF Jr., White KR. Sensorineural hearing loss in children. Lancet 2005;365:879-90.|
|9||Augustine AM, Jana AK, Kuruvilla KA, Danda S, Lepcha A, Ebenezer J, et al. Neonatal hearing screening – Experience from a tertiary care hospital in Southern India. Indian Pediatr 2014;51:179-83.|
|10||Crifò S, Lazzari R, Salabè GB, Arnaldi D, Gagliardi M, Maragoni F. A retrospective study of audiological function in a group of congenital hypothyroid patients. Int J Pediatr Otorhinolaryngol 1980;2:347-55.|
|11||Chou YH, Wang PJ. Auditory brainstem evoked potentials in early-treated congenital hypothyroidism. J Child Neurol 2002;17:510-4.|
|12||Rovet J, Walker W, Bliss B, Buchanan L, Ehrlich R. Long-term sequelae of hearing impairment in congenital hypothyroidism. J Pediatr 1996;128:776-83.|
|13||Hashemipour M, Hovsepian S, Hashemi M, Amini M, Kelishadi R, Sadeghi S. Hearing impairment in congenitally hypothyroid patients. Iran J Pediatr 2012;22:92-6.|
|14||Bailey T. Auditory pathways and processes: Implications for neuropsychological assessment and diagnosis of children and adolescents. Child Neuropsychol 2010;16:521-48.|
|15||Prabhu SR, Mahadevan S, Jagadeesh S, Suresh S. Congenital Hypothyroidism: Recent Indian data. Indian J Endocrinol Metab 2015;19:436-7.|
|16||Sareen N, Pradhan R. Need for neonatal screening program in India: A national priority. Indian J Endocrinol Metab 2015;19:204-20.|
|17||The Association of Clinical Biochemistry. UK Guidelines for the Use of Thyroid Function Tests, British Thyroid Association's; 2006. Available from: http://www.british-thyroid-association.org. [Last accessed on 2015 Sep 15].|
|18||Dayal D, Sindhuja L, Bhattacharya A, Sodhi KS, Sachdeva N. Agenesis and not ectopia is common in North Indian children with thyroid dysgenesis. Indian J Endocrinol Metab 2014;18 Suppl 1:S97-9.|
|19||Dayal D, Naganur SH, Siakia BK, Singh B. Thyroid dysfunction and autoantibodies in first degree relatives of North Indian children with autoimmune thyroiditis. Thyroid Res Pract 2015;12:96-9.|
|20||François M, Bonfils P, Leger J, Czernichow P, Narcy P. Role of congenital hypothyroidism in hearing loss in children. J Pediatr 1994;124:444-6.|
|21||Dayal D, Jain P, Panigrahi I, Bhattacharya A, Sachdeva N. Thyroid dysfunction in Indian children with Down syndrome. Indian Pediatr 2014;51:751-2.|
|22||Dayal D, Sindhuja L, Bhattacharya A, Bharti B. Advanced maternal age in Indian children with thyroid dysgenesis. Clin Pediatr Endocrinol 2015;24:59-62.|
|23||Sindhuja L, Dayal D, Sodhi KS, Sachdeva N, Bhattacharya A. Thyroid dysfunction and developmental anomalies in first degree relatives of children with thyroid dysgenesis: World J Pediatr 2015;ŠDec 18. doi: 10.1007/s12519-015-0061-z. [Epub ahead of print]|
|24||Anjana Y, Vaney N, Tandon OP, Madhu SV. Functional status of auditory pathways in hypothyroidism: Evoked potential study. Indian J Physiol Pharmacol 2006;50:341-9.|
|25||Kalpana R, Chamyal PC. Study of prevalence and aetiology of the hearing loss amongst school going children. Indian J Otolaryngol Head Neck Surg 1997;49:142-4.|