|Year : 2014 | Volume
| Issue : 4 | Page : 191-195
Effects of acute thyroxine depletion on hearing in differentiated thyroid carcinoma patients
Zekiye Hasbek1, Canan Filiz Karakus2, Emine Elif Altuntas3, Fatih KiliÁli4
1 Department of Nuclear Medicine, School of Medicine, Cumhuriyet University Campus, 58140, Turkey
2 Department of Otorhinolaryngology, Ministry of Health, Hatay Antakya Public Hospital, Hatay, Turkey
3 Department of Otolaryngology, School of Medicine, Cumhuriyet University Campus, 58140, Turkey
4 Department of Endocrinology and Metabolic Diseases, School of Medicine, Cumhuriyet University Campus, 58140 Sivas, Turkey
|Date of Web Publication||13-Dec-2014|
Emine Elif Altuntas
Department of Otolaryngology, School of Medicine, Cumhuriyet University Campus, 58140 Sivas
Source of Support: None, Conflict of Interest: None
Introduction: Radioiodine ablation refers to the destruction of functioning remnants of normal thyroid tissue or metastatic foci remaining after thyroidectomy. Effective thyroid ablation requires adequate stimulation of thyroid-stimulating hormone. Our aim in this study was to evaluate the hearing changes of patients before ablation therapy in the iatrogenic hypothyroid period, which has been constituted with the purpose of treatment success and following the ablation therapy in the euthyroid period 1 month after the thyroid hormone (TH) replacement therapy was initiated. Materials and Methods: Patients who were diagnosed with thyroid cancer, treated with total/near-total thyroidectomy and referred for 131 I therapy or low-dose 131 I whole body scan were included in our study. Hearing tests as high-frequency audiometry, autoacoustic emission and tympanometry were made during hypothyroid and euthyroid periods on all the patients included in the study. Results: In the present study were enrolled 75 patients with a mean age of 46.6 ± 12 years (range: 19-69 years). In hypothyroid period, while there was not any hearing-loss in 124 of 150 (82.7%) ears of 75 patients; mild hearing-loss in 18 (12%) ears, moderate hearing-loss in 7 (4.7%) ears and severe hearing-loss in 1 (0.07%) ear were detected. In euthyroid period, while there was not any hearing-loss in 132 of 150 (88%) ears; there were mild hearing-loss in 11 (7.3%), moderate hearing-loss in 6 (4%), and severe hearing-loss in 1 (0.07%) ear. However, there could not be found any significant difference between hearing levels of patients before and after treatment (P = 0.317). Conclusion: Although THs play an important role in the physiology of hearing, the hypothyroidism made in 4 weeks period causes serious damages on hearing functions of patients. However, with regard to temporary hearing losses that hearing levels could improved with treatment, we believe that hearing should also be questioned in the follow-up of patients with differentiated thyroid cancer.
Keywords: Hearing-loss, Hypothyroidism, Radioiodine, Thyroid cancer
|How to cite this article:|
Hasbek Z, Karakus CF, Altuntas EE, KiliÁli F. Effects of acute thyroxine depletion on hearing in differentiated thyroid carcinoma patients. Indian J Otol 2014;20:191-5
|How to cite this URL:|
Hasbek Z, Karakus CF, Altuntas EE, KiliÁli F. Effects of acute thyroxine depletion on hearing in differentiated thyroid carcinoma patients. Indian J Otol [serial online] 2014 [cited 2020 Jan 19];20:191-5. Available from: http://www.indianjotol.org/text.asp?2014/20/4/191/146937
| Introduction|| |
There are several histological types and subtypes of thyroid carcinoma with different cellular origins, characteristics, and prognoses. Differentiated thyroid cancer (DTC), which includes papillary and follicular histologies, is a common malignancy and is increasing in incidence. It carries a favorable prognosis compared with other cancers. However, optimal outcomes are achieved only via coordinated multimodal therapy. Of these treatments, surgery is the principal of initial management. Most patients should undergo thyroidectomy with concomitant central neck (Level VI) lymph node dissection. 131 I ablation therapy is a successful form of treatment that aims to destroy the remaining residual tissue and/or metastatic tissue after surgical treatment in patients with DTCs.  Effective thyroid ablation requires adequate stimulation of thyroid-stimulating hormone (TSH). Two methods of preparation are available: Thyroid hormone (TH) withdrawal for 4-6 months and consequent hypothyroidism, or administration of recombinant human thyrotropin with the patient continuing L-thyroxine (LT4) therapy. 
Thyroid hormone deficiency can cause severe cognitive dysfunction and deafness. One of the most important dysfunctions of the thyroid gland is hypothyroidism in which the production or function of THs is impaired, resulting in generalized reduction of the metabolism of all systems.  Hypothyroidism is a cause of genetically and environmentally induced deafness.  Hearing-loss in hypothyroidism has been reported by many authors but its pathophysiology is unclear. However, it is been known that hypothyroidism causes decrease in cellular energy production. The real incidence of hearing-loss in patients with hypothyroidism is still uncertain, and it may affect 25% of the patients with acquired hypothyroidism and 35-50% of the patients with congenital hypothyroidism.  In literature, there are some clinic and animal studies that hypothyroidism induced hearing-loss was evaluated by various audiological methods. ,, Tests as brainstem auditory evoked potentials (BAEP) and otoacoustic emission (OAE) can be used in evaluation of hearing functions of patients with hypothyroidism.
Our aim in this study was to evaluate the hearing-loss changes of patients with high-frequency audiometry, otoacoustic emission and tympanometry, after total/near-total thyroidectomy, diagnosed with differentiated thyroid carcinoma, within the deep hypotroidism period that iatrogenically generated during high-dose ablation therapy, and following the ablation therapy in the euthyroid period 1 month after the TH replacement therapy was initiated.
| Materials and Methods|| |
Patients who were diagnosed with DTC, treated with bilateral total/near-total thyroidectomy and referred for ablation therapy with high-dose 131 I between June 2011 and June 2012 were included in our study. This study was performed in accordance with the principles of Declaration of Helsinki and approved by the Cumhuriyet University Research Ethics Committee. Oral and written consent of the patients were obtained. All patients were evaluated twice in both hypothyroid and euthyroid period. LT4 was withdrawn for 4 weeks for adequate stimulation of TSH before ablation therapy (hypothyroid period). Serum thyroglobulin (Tg), antithyroglobulin antibody (anti-TgAb), free T3 (fT3), fT4 and TSH levels were recorded before ablation therapy in all patients after adequate thyroxine withdrawal for 4-5 weeks. The reference range of free T4, free T3 and TSH were between 0.7 and 1.48 ng/dL, 1.71-3.71 pg/mL and 0.35-4.94 mIU/mL, respectively. After 131 I ablation therapy, all patients were begun taking L-T4 preparation (euthyroid period). Serum Tg, anti-TgAb, fT3, fT4 and TSH levels were measured again 1 month after the ablation therapy.
Exclusion criteria were: History of ear surgery; ear or head trauma; acute or chronic otitis media; syphilis; other malignancy; upper respiratory tract infection at examination; intake of ototoxic drugs or employment in a noisy environment; the diseases which cause hearing-loss as hypertension, liver failure, renal failure; radiotherapy or chemotherapy treatment in the last month; vascular disease; congenital cochlear malformation; neurologic disease (cause a loss of hearing). Moreover, patients who did not agree on taking hearing tests, who had ear infection symptoms within the euthyroid period, who did not keep on hearing and hormone levels follow-up and who did not want to continue to the study were also excluded from the study.
Hearing tests as high-frequency audiometry, autoacoustic emission and tympanometry were made during hypothyroid and euthyroid periods on all the patients included in the study. All the patients were evaluated by the same physician who was unaware of the TH state of the patients at ear, nose and throat (ENT) clinic. Detailed anamnesis information, thyroid function test results, otoscopic examination symptoms, high-frequency audiogram and otoacoustic emission findings of all patients included in the study were recorded with patient follow-up forms. Air and bone conduction thresholds of patients were measured by clinical audiometer device (Interacoustics AC 40 Clinical Audiometer, Assens, Denmark) which calibrated according to ISO standards. All audiological tests were made while other ear was masked. Pure tone hearing thresholds according to international standards were determined by air and bone conduction for frequencies 0.25, 0.5, 1, 2, 4, 6, 8 and 12 kHz. For whom the pure tone threshold of hearing was up to 0 20 dBs the hearing was classified as normal, for those between 21 and 40 dBs as mild, for those between 41 and 60 dBs as moderate, for those between 61 and 80 dBs as severe, for those between 80 and 100 dBs as deep and for those over 100 dBs the hearing was classifies as total hearing-loss. After that Transient Evoked Otoacoustic Emission (TEOAE) test was made with TEOAE device (MAICO ERO-SCAN TEOAE) on all patients. TEOAE testing and analysis were made by a commercial device (Maico, ERO Scan Analyzer, GmbH Salzufer, 13/14, 10587, Berlin GE) that calibrated before it was used. During the test, disposable prop were used to close the ear canal. When testing is complete, if there was a response to TEOAE (better hearing than 30 decibels), the result was seen as "PASS" on the screen, while it was seen as "REFER" for ones that there was not any response (hearing-loss range was 30 decibels or more). Screening test was repeated in the ear we get "REFER" as result. Stimulant in form of klick occurred in the frequency range 0.7-4 kHz and 83 dB/SPL (±3 dB) degree of density. This test was recorded in each session separately for the right and left ears. The results were recorded one by one in the frequency band width of 1, 5-4 kHz and in 1.5, 2, 2.5, 3, 3.5 and 4 kHz frequencies for TEOAE. In the band width of 1, 5-4 kHz, the average amplitude of TEOAE below 6 dB was meant that there was no response to otoacoustic emission.
Statistical Package of Social Science (SPSS Inc., Chicago, IL) for Windows version 14.0. software was used for the statistical analysis. The Chi-square test was applied to evaluate the statistical significance of the parameters; significance levels were presented as P values. It was assumed that the observed differences were statistically significant at the P < 0.05 level. Also "McNemar's test," "Unpaired t-test," and "Correlation Analysis" were applied.
| Results|| |
A total of 75 patients with an age range of 19-69 years (mean: 46.6 ± 12 years) were included in the study. Of the patients, 15 (20%) were males with a mean age of 48.4 ± 12 (22-69) years while, the 60 (80%) were females with a mean age 46.1 ± 12 (19-66). The difference between genders was considered to be insignificant in terms of age (P > 0.05).
The difference was found to be significant when fT3, fT4 and TSH levels of hypothyroid and euthyroid periods were compared and significant differences were found (P = 0.001). While fT3 levels: 1.28 ± 0.22, fT4 levels: 0.42 ± 0.06, TSH levels: 70.96 ± 26.19 during hypothyroid period; fT3 levels: 2.86 ± 0.58, fT4 levels: 1.21 ± 0.22 and TSH level: 2.88 ± 1.66 during euthyroid period [Table 1].
|Table 1: Comparison of thyroid hormone levels and TSH levels in hypothyroid period and euthyroid period (P<0.05*)|
Click here to view
In hypothyroid period, while there was not any hearing-loss in 124 of 150 (82.7%) ears of 75 patients; mild hearing-loss in 18 (12%) ears, moderate hearing-loss in 7 (4.7%) ears and severe hearing-loss in 1 (0.07%) ear were detected. In euthyroid period, while there was not any hearing-loss in 132 of 150 (88%) ears; there were mild hearing-loss in 11 (7.3%), moderate hearing-loss in 6 (4%), and severe hearing-loss in 1 (0.07%) ear. However, there could not be found any significant difference between hearing levels of patients before and after treatment (P = 0.317) [Table 2].
|Table 2: Comparison of the patients categorized by their airway threshold values in hypothyroid period and euthyroid period (P=0.317)|
Click here to view
When we compared the hypothyroid and euthyroid period's average value of pure tone of individuals participating in the study; it has been recorded that the pure tone average values in euthyroid period decreased, and this difference was found as significant. However, while there were negative relationship parameters between hypothyroid period pure tone averages and fT3 (r = −0.19) and fT4 (r = −0.14); a positive relation, but weak correlation were found with the TSH (r = 0.07). The positive relation between euthyroid period pure tone averages and fT3 (r = 0.04) and fT4 (r = 0.13) and its negative correlation with TSH (r = −0.22) was also weak.
When the values of airway hearing thresholds in both hypothyroid and euthyroid periods which measured at different frequencies were compared; airway thresholds in all frequencies but 8000 Hz were higher in hypothyroid period, lower in euthyroid period. Differences between the measurements were significant (P < 0.05) [Table 3]. Variation of airway hearing thresholds of the individuals at different frequencies in hypothyroid and euthyroid periods was shown in [Figure 1].
|Figure 1: Variation of airway hearing thresholds of the individuals at different frequencies in hypothyroid and euthyroid periods|
Click here to view
|Table 3: Comparison of the airway hearing thresholds of individuals in different frequences within hypothyroid and euthyroid periods|
Click here to view
When otoacoustic emission results of 150 ears of 75 patients involved in the study in hypotyroid and eutyroid periods were compared; the "PASS" result was recorded for 136 (90.66%) ears, the "REFER" result was recorded for 14 (9.33%) ears in hypothyroid period; on the other hand, the "PASS" result was recorded for 142 (94.66%) ears and the "REFER" result were recorded for 8 (5.33%) ears in euthyroid period.
| Discussion|| |
Thyroid cancers are the most common cancers of the endocrine system. Ablation therapy with 131 I is a valuable adjunct in differentiated thyroid carcinoma therapy for ablation of postsurgical residual tissue in the neck and for eradication of functioning local and distant thyroid metastases. TH medication are withdrawn until TSH > 30 μU/mL; this is usually 4-5 weeks after discontinuing levothyroxine. Patients should follow a low-iodine diet for 10-14 days (iodized salt, milk, eggs, seafood, chocolate etc.) before ablation therapy. After ablation therapy, TH replacement should be instituted 3-5 days after the administration of therapy. 
Worldwide, not enough iodine in the diet and Hashimoto's thyroiditis are the most common causes of hypothyroidism. Previous treatment with radioactive iodine is a less common cause. Hypothyroidism is characterized by low serum free thyroxine concentrations with elevated serum TSH concentrations. Auditory impairment has been related more largely to congenital hypothyroidism than to acquired hypothyroidism.  Hearing deficit is an invisible abnormality, but has major consequences for educational and social skills if not detected. Therefore, there is a relationship among especially the early diagnosis of congenital hypothyroidism and the age of beginning the treatment of TH replacement and the hearing-loss. , Hearing-loss may develop during the acquired hypothyroidism. However, it has not been determined precisely yet whether there is any relationship between the severity of hearing-loss and the degree and reversibility of hypothyroidism.  Despite there are many studies in literature about the hearing-loss caused by congenital hypothyroidism, studies on acquired hypothyroidism are very limited. In their study including only 7 patients with hypothyroidism, Howarth and Lloyd  have detected that the hearing-loss of 4 of these patients improved after treatment.
Ear development and hearing function depend on THs through different pathways, including both inner ear morphology as well as neurological processes.  In ENT, hearing-loss accompanied with cochleovestibular symptoms such as tinnitus and dizziness is the most commonly encountered symptom of hypothyroidism. Hearing-loss observed in hypothyroidism is a mild to moderate bilateral sensorineural hearing-loss.  It is not possible to distinguish cochlear from retrocochlear hearing-loss by clinical examination alone; further testing as autoacoustic emission test is required.
When Di Lorenzo et al.  evaluated the hearing degrees of patients with hyperthyroidism before and 6-12 months after the treatment by using auditory brainstem responses (ABR), the findings showed that there was a relationship between the degree of hypothyroidism and ABR abnormalities and hearing-loss was reversible, although it's not always true. Similarly, Anand et al.  reported that, detected reduction in the audiometric thresholds and BAEP changes in 16 of 20 patients with hypothyroidism without treatment. After the hormonal replacement treatment for a period of 3.7 months, there was a remarkable improvement in the audiometric threshold; however, the BAEP results maintained altered, there was also a reduction on the absolute latency amplitudes on waves I, III and V and increase in the absolute latency in wave V and interpeaks LI-III and L I-V. Besides, in the study of Parazzini et al.  on 29 congenital hypothyroid patients and 68 healty babies, no correlation was found between outer hair cell dysfunction and hypothyroidism. Regarding the Thornton and Jarvis  study on 14 patients with hyperthyroidism and 21 patients with hypothyroidism; hyperthyroid patients did not differ significantly from the control group. However, the audiometric findings for the hypothyroid group showed that, 36% of the group had a better hearing for frequency average of >25 dB. But they said that the situation might have occurred because of the low body temperature of patients. In their study on 30 patients of control group and 30 patients of hypothyroidism group, Santos et al.  reported that, audiological changes were not associated with serum TSH or T4 levels. The first study in the literature about hearings of cases with chronic hypothyroidism and acute hypothyroidism was Jahnke et al.  study. They demonstrated that, hearing-loss was seen in 45% of the patients with chronic hypothyroidism. They demonstrated that, there was hair cell damage in 13 of the patients with chronic hypothyroidism. This loss was mild to moderate in over 90% of the cases and 50% of the patients showed a small improvement in hearing after thyroid substitution therapy. Dokianakis et al.  presented the audiometric findings on 23 patients with hypothyroidism for a minimum of 4 months to a maximum of 20 years. In 12 patients, there was a definite impairment of hearing before the substitution therapy. And they found that, the audiometric measurements after an adequate substitution therapy of minimum 4 months have shown a definite improvement of hearing-loss. We detected decrease in hearing levels of the patients with acquired hypothyroidism in pretreatment period, on the other hand improvement in hearing in the posttreatment euthyroid period. While the average of pure tone thresholds of our patients was 16.61 ± 11 in hypothyroid period, it was 15.39 ± 11 in euthyroid period and this difference was found statistically significant. With regard to our study, the improvement in hearing within the euthyroid period following hypothyroid period make us think that acute severe hypothyroidism has a temporary impact on hearing. As a consequence, untreated hypothyroidism is known to impair hearing but the impact of temporary hypothyroidism on hearing is unknown. Although only a limited numbers of studies have directly investigated the relationship between iodine deficiency and auditory function. Even we could not find any study on hearings changes of rapidly growing acute hypothyroid cases during our literature search, such as the cases in our study. With their study in 1982, Anniko and Rosenkvist  investigated the morphologic changes in the inner ears of rats which were experimentally made hypothyroid. In their study they found that the first structure of the inner ear to be affected by hypothyroidism was tectorial membrane and thickening of the basilar membrane was indicated in many, but not all, specimens and in some control animals and may be coincidental. As a result of this experimental study, they emphasized that the morphologic changes seen in hypothyroid period might be reversible by treatment. We don't know the reason of temporary increase of threshold in hearing levels in hypothyroid/euthyroid periods in our study. However, changes in the morphology of the inner ear might be effective on the basis of these temporary changes, as in the findings of the study of Anniko and Rosenkvist.  Therefore, believe that future studies need to be done on this issue.
| Conclusion|| |
Although THs play an important role in the physiology of hearing, the hypothyroidism made in 4 weeks period causes serious damages on hearing functions of patients. However, with regard to temporary hearing losses that hearing levels could improve with treatment, we believe that hearing should also be questioned in the follow-up of patients with DTC.
| References|| |
Mazzaferri EL. The diagnosis and imaging of thyroid cancer. In: Amdur JA, Mazzaferri EL, editors. Essentials of Thyroid Cancer Management. Springer Science+Business Media, Inc.; 2005. p. 39-120.
Schroeder PR, Haugen BR, Pacini F, Reiners C, Schlumberger M, Sherman SI, et al.
A comparison of short-term changes in health-related quality of life in thyroid carcinoma patients undergoing diagnostic evaluation with recombinant human thyrotropin compared with thyroid hormone withdrawal. J Clin Endocrinol Metab 2006;91:878-84.
Annerbo S, Lökk J. A clinical review of the association of thyroid stimulating hormone and cognitive impairment. ISRN Endocrinol 2013;2013:856017.
Fang Q, Giordimaina AM, Dolan DF, Camper SA, Mustapha M. Genetic background of Prop1(df) mutants provides remarkable protection against hypothyroidism-induced hearing impairment. J Assoc Res Otolaryngol 2012;13:173-84.
Vanasse M, Fischer C, Berthezène F, Roux Y, Volman G, Mornex R. Normal brainstem auditory evoked potentials in adult hypothyroidism. Laryngoscope 1989;99:302-6.
Di Lorenzo L, Foggia L, Panza N, Calabrese MR, Motta G, Tranchino G, et al.
Auditory brainstem responses in thyroid diseases before and after therapy. Horm Res 1995;43:200-5.
Anand VT, Mann SB, Dash RJ, Mehra YN. Auditory investigations in hypothyroidism. Acta Otolaryngol 1989;108:83-7.
Parazzini M, Ravazzani P, Medaglini S, Weber G, Fornara C, Tognola G, et al.
Click-evoked otoacoustic emissions recorded from untreated congenital hypothyroid newborns. Hear Res 2002;166:136-42.
American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, et al.
Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009;19:1167-214.
Melse-Boonstra A, Mackenzie I. Iodine deficiency, thyroid function and hearing deficit: A review. Nutr Res Rev 2013;26:110-7.
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.
Wasniewska M, De Luca F, Siclari S, Salzano G, Messina MF, Lombardo F, et al.
Hearing loss in congenital hypothalamic hypothyroidism: A wide therapeutic window. Hear Res 2002;172:87-91.
Comer DM, McConnell EM. Hypothyroid-associated sensorineuronal deafness. Ir J Med Sci 2010;179:621-2.
Howarth AE, Lloyd HE. Perceptive deafness in hypothyroidism. Br Med J 1956;1:431-3.
Ritter FN. The effects of hypothyroidism upon the ear, nose and throat. A clinical and experimental study. Laryngoscope 1967;77:1427-79.
Thornton AR, Jarvis SJ. Auditory brainstem response findings in hypothyroid and hyperthyroid disease. Clin Neurophysiol 2008;119:786-90.
Jahnke K, Maas B, Mödder G. Hypacusis in acquired hypothyroidism (author's transl). HNO 1979;27:1-6.
Santos KT, Dias NH, Mazeto GM, Carvalho LR, Lapate RL, Martins RH. Audiologic evaluation in patients with acquired hypothyroidism. Braz J Otorhinolaryngol 2010;76:478-84.
Dokianakis G, Ferekidis E, Pantazopoulos P. Hearing loss and hyperthyroidism (author's transl). Arch Otorhinolaryngol 1978;219:351-3.
Anniko M, Rosenkvist U. Tectorial and basal membranes in experimental hypothyroidism. Arch Otolaryngol 1982;108:218-20.
[Table 1], [Table 2], [Table 3]