- Email: [email protected]
Effects of Radioactive Iodine Ablation Therapy on Voice Quality
ARTICLE IN PRESS Effects of Radioactive Iodine Ablation Therapy on Voice Quality *I˙mran Aydog˘du, †Yavuz Atar, †Ziya Saltürk, †Hüseyin Sarı, †Enes Ataç, †Zeynep Aydog˘du, †Muzaffer I˙nan, †Gökhan Mersinliog˘lu, and †Yavuz Uyar, *†Turkey Summary: Objective. The goal of this study was to evaluate the effects of radioactive iodine ablation therapy on voice quality of patients diagnosed with well-differentiated thyroid carcinoma. Methods. We enrolled 36 patients who underwent total or subtotal thyroidectomy due to well-differentiated thyroid carcinoma. Voice recordings from patients were analyzed for acoustic and aerodynamic voice. The Voice Handicap Index-10 was used for subjective analysis. The control group consisted of 36 healthy participants. Results taken before and after therapy were compared statistically. Results. There were no differences in the results taken before and after therapy for the radioactive iodine ablation group. The Voice Handicap Index-10 results did not differ between groups before and after therapy. Conclusion. Radioactive iodine ablation therapy has no effect on voice quality objectively or subjectively. Key Words: Acoustic analysis–Radioactive iodine therapy–Total thyroidectomy–Voice–Well-differentiated thyroid cancer. INTRODUCTION Although rare, thyroid carcinoma is the most frequent of the endocrine system carcinomas, responsible for approximately 90% of these cancers.1–3 Annual incidence of well-differentiated thyroid carcinoma is 0.07% and continues to increase each year.2,4 Treatment is typically a combination of surgery (eg, radioactive iodine ablation [RIA] and external radiotherapy) and hormone replacement (eg, thyroid-stimulating hormone suppression and thyroid kinase inhibitors).5 RIA is an important therapy used to treat follicular and papillary thyroid carcinomas because it ablates remnant tumor tissue and metastatic foci. RIA emits beta radiation that extends 1–2 mm in diameter. As a result, it may cause mild and temporary thyroiditis, epithelial edema, follicular irregularity, mononuclear cell infiltration, and necrosis.6 Thyroidectomy might cause dysphonia due to recurrent laryngeal nerve injury or superior laryngeal nerve injury. On the other hand, some minor changes, including lower fundamental frequency (F0), might be seen after 1 year of follow-up.7 In addition, edema and inflammation caused by intubation, strap muscle dysfunction and scars, and elevation problems might cause voice changes.8–12 Injury to salivary gland is one of the most prominent side effects of RIA treatment and might cause vocal changes. In addition, inflammation and necrosis on the remnant thyroid tissue might cause some changes in voice by effecting recurrent laryngeal nerve.13–15 To the best of our knowledge, Ryu et al13 published the results of RIA therapy in a long-term period and found no changes on voice quality in well-differentiated thyroid carcinoma patients. The goal of this study was to investigate the early effects of RIA therapy on these patients. Accepted for publication February 17, 2016. From the *Bahçelievler Government Hospital ENT Clinic, Turkey; and the †Okmeydanı Training and Research Hospital ENT Clinic, Turkey. Address correspondence and reprint requests to I˙mran Aydog˘du, Kocasinan Merkez Mahallesi Karadeniz Caddesi No: 48, Bahçelievler, Istanbul, Turkey. E-mail: [email protected] Journal of Voice, Vol. ■■, No. ■■, pp. ■■-■■ 0892-1997 © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jvoice.2016.02.013
MATERIALS AND METHODS International review board approval was granted by the Okmeydani Training and Research Hospital’s Ethics Committee. This study was conducted at the Okmeydani Training and Research Hospital Ear, Nose and Throat Clinic between March and April 2015. We enrolled 36 patients who underwent total or subtotal thyroidectomy for well-differentiated thyroid carcinoma and planned to have RIA therapy at a dosage of between 1.0 and 2.5 GBq. Twenty-eight patients had underwent total thyroidectomy and eight patients had underwent subtotal thyroidectomy. All patients underwent a complete otolaryngological examination. Patients with upper respiratory tract infections, history of laryngeal surgery or pathology, pulmonary issues, history of head and neck radiotherapy, and reflux or obstructive sleep apnea, and were tobacco users, were excluded. Laryngeal examinations were performed with rigid 70° endoscope (Karl Storz Telecam DX II, Tuttlingen, Germany). The control group consisted of 36 healthy participants. We also compared the results based on gender. All subjects underwent a complete head and neck examination, as well as acoustic and aerodynamic analyses. Voices were recorded using a dynamic microphone placed 15 cm from the lips 2 hours before the treatment and on the 20th day after treatment. Following deep inspiration, subjects were prompted to say the vowel “ah” for as long as they could. This was repeated three times, and the longest recorded time was accepted as the subject’s maximum phonation time (MPT). Additionally, subjects were asked to read a phonetically balanced passage from a famous Turkish story titled “Diyet” for 40 s in a relaxed voice. The Praat software (Version 4.4.13; Boersma and Weenink, University of Amsterdam, Amsterdam, Netherlands) was used for acoustic analysis. The F0, jitter, shimmer, and harmonic-to-noise ratio were determined during acoustic voice analysis. Subjective evaluation was performed using the Voice Handicap Index-10 (VHI-10). The Turkish version of the VHI-10, validated by Kiliç et al,16 consists of 10 questions and is scored between 0 (never) and 4 (always). This questionnaire includes emotional, functional, and physical subscales consisting of four, three, and three questions, respectively.
ARTICLE IN PRESS 2
Journal of Voice, Vol. ■■, No. ■■, 2016
Statistical analysis of the data was conducted using SPSS ver. 17.0 (SPSS IBM USA). After analysis, data were presented using descriptive statistical methods (mean ± standard deviation). Parametric independent sample t-tests were used for comparisons between groups. Results were evaluated using 95% confidence intervals, with the level of significance set as P < 0.05. RESULTS There were 24 (66.6%) papillary thyroid and 12 (33.3%) follicular carcinoma cases. The RIA group consisted of 25 female and 11 male patients with a mean age of 38.7 years (range: 18–63 years). The control group consisted of 24 female and 12 male subjects with a mean age of 36.6 years (range: 20–61 years). Table 1 lists the results of the acoustic and aerodynamic analyses taken before and after RIA therapy, and Table 2 lists the
results of male patients in comparison with the male control group. Table 3 illustrates the female patients in comparison with the female control group. Our results indicated no significant difference between the groups. VHI-10 results before and after RIA therapy were not significant (6.07 ± 3.54 and 5.56 ± 3.23, respectively). In addition, there were no significant differences in the VHI-10 results between the RIA group and the control group. DISCUSSION The incidence of well-differentiated thyroid carcinoma continues to increase worldwide.2,4 The first step to treating this cancer is surgery, involving resection of the tumor and metastatic foci.17 Following surgery, RIA therapy is performed to eliminate remnant thyroid tissue and metastatic foci. This therapy is effective because
TABLE 1. Comparison of Radioactive Iodine Therapy Group and Control Group Parameters MPT F0 Jitter Shimmer HNR Intensity
Before RAI (n = 36) Mean ± SD
After RAI (n = 36) Mean ± SD
Control Group (n = 36) Mean ± SD
P
16.51 ± 2.95 205.45 ± 70.40 0.33 ± 0.19 1.83 ± 0.59 20.69 ± 3.01 70.45 ± 5.40
17.11 ± 2.86 200.50 ± 71.20 0.37 ± 0.23 1.89 ± 0.61 21.63 ± 3.11 69.95 ± 5.60
16.99 ± 2.92 202.52 ± 72.40 0.34 ± 0.21 1.88 ± 0.69 20.99 ± 3.27 69.70 ± 5.51
0.365 0.645 0.622 0.875 0.142 0.432
Abbreviations: F0, fundamental frequency; HNR, harmonic-to-noise ratio; MPT, maximum phonation time; RAI, radioactive iodine therapy; SD, standard deviation.
TABLE 2. Comparison of Results of Male Patients and Male Control Groups Parameters MPT F0 Jitter Shimmer HNR Intensity
Before RAI (n = 11) Mean ± SD
After RAI (n = 11) Mean ± SD
Control Group (n = 12) Mean ± SD
P
17.48 ± 2.87 163.71 ± 42.37 0.32 ± 0.18 1.86 ± 0.47 20.59 ± 2.99 72.01 ± 5.33
16.98 ± 3.01 161.69 ± 46.91 0.36 ± 0.20 1.91 ± 0.59 21.89 ± 3.01 70.21 ± 5.55
17.12 ± 2.81 166.51 ± 44.33 0.35 ± 0.19 1.90 ± 0.68 20.68 ± 3.21 71.34 ± 5.72
0.404 0.561 0.701 0.821 0.199 0.429
Abbreviations: F0, fundamental frequency; HNR, harmonic-to-noise ratio; MPT, maximum phonation time; RAI, radioactive iodine therapy; SD, standard deviation.
TABLE 3. Comparison of Results of Female Patients and Female Control Groups Parameters MPT F0 Jitter Shimmer HNR Intensity
Before RAI (n = 25) Mean ± SD
After RAI (n = 25) Mean ± SD
Control Group (n = 24) Mean ± SD
P
15.98 ± 2.32 221.41 ± 76.46 0.34 ± 0.22 1.82 ± 0.60 21.02 ± 3.23 70.01 ± 5.51
16.23 ± 2.77 219.98 ± 74.90 0.34 ± 0.17 1.88 ± 0.66 20.93 ± 3.17 68.99 ± 5.49
16.71 ± 3.02 225.71 ± 69.11 0.33 ± 0.24 1.87 ± 0.65 21.76 ± 3.14 69.21 ± 5.31
0.693 0.621 0.453 0.757 0.221 0.515
Abbreviations: F0, fundamental frequency; HNR, harmonic-to-noise ratio; MPT, maximum phonation time; RAI, radioactive iodine therapy; SD, standard deviation.
ARTICLE IN PRESS I˙mran Aydog˘du et al
Effects of Radioactive Iodine Ablation Therapy
radioactive iodine has a high affinity to thyroid tissue, and thus can be used to treat well-differentiated thyroid carcinoma. In addition, iodine-131 is economical and user-friendly. Beta radiation emitted from iodine-131 causes damage to follicular cells in a dose-dependent manner. The half-life of iodine-131 is 8 days, which is long enough to treat the carcinoma.18 Following iodine treatment, necrosis can result, leading to fibrosis.6 There are few case reports that mention recurrent laryngeal nerve damage caused by RAI therapy. However, it has been reported that edema from this therapy causes unilateral recurrent laryngeal nerve paralysis.19–24 Of these five cases, two had spontaneous healing within 6 months and two healed within 18 months. None of these reports analyzed voice quality. Although RIA therapy appears to be safe, vocal outcomes should be investigated, especially for patients that are voice professionals. The first study to investigate the effects of RIA therapy on voice quality was performed by Isolan-Cury et al.25 In this study, they performed an acoustic analysis on Graves’ disease patients who underwent RIA therapy. They took recordings before therapy and on days 2, 4, and 18 following therapy. They observed no difference in MPT, F0, and jitter.25 Because voice quality can be affected by a number of variables, patient selection is extremely important. Patients who were below or above a certain age were not included in this study. We also excluded patients with pathologies that can affect voice quality (eg, laryngeal and pulmonary pathologies). MPT reflects prolonged vocalization and continuous speech. It is related to the resistance and force generated at the glottal region.26 F0, the lowest frequency, is the main parameter of the listener’s perception of the speaker’s pitch and is determined primarily by the elasticity, tension, and mass of the vocal folds.27 Jitter and shimmer percentages represent the vibrational action of the glottis, as well as the short-term (period-to-period) irregularity of the pitch and of the peak-to-peak amplitude of the voice, respectively.28 The results from our study revealed no difference in voice quality between the RIA therapy and control groups. CONCLUSIONS RIA therapy had no adverse effect on voice quality objectively and subjectively. Studies with larger patient cohorts and that investigate cepstral analysis of speech will be necessary to completely understand the effects of RIA therapy on voice quality. REFERENCES 1. Jameson JL, Weetman AP. Disorders of the thyroid gland. In: Kasper DL, Fauci AS, Longo DL, et al., eds. Harrison’s Principles of Internal Medicine, 16th Edition. New York: The McGraw Hill Companies; 2005:2014–2126 [Ch 320]. 2. Luster M, Clarke SE, Dietlein M, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35:1941–1959. 3. Mazzaferri EL, Kloos RT. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 2001;86:1447–1463.
3
4. Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer. 2009;115:3801–3807. 5. McLeod DSA, Carruthers K, Kevat DAS. Optimal differentiated thyroid cancer management in the elderly. Drugs Aging. 2015;3:283–294. 6. Davies T, Larsen P. Thyrotoxicosis. In: Williams RH, Larsen PR, eds. Williams Textbook of Endocrinology. 10a ed. Philadelphia: Saunders; 2003:374–396. 7. Minni A, Ruoppolo G, Barbaro M, et al. Long-term (12 to 18 months) functional voice assessment to detect voice alterations after thyroidectomy. Eur Rev Med Pharmacol Sci. 2014;18:1704–1708. 8. Hong KH, Kim YK. Phonatory characteristics of patients undergoing thyroidectomy without laryngeal nerve injury. Otolaryngol Head Neck Surg. 1997;117:399–404. 9. Akyıldız S, Ogut F, Akyıldız M, et al. Multivariate analysis of objective voice changes after thyroidectomy without laryngeal nerve injury. Arch Otolaryngol Head Neck Surg. 2008;134:596–602. 10. Sinagra DL, Montesinos MR, Tacchi VA, et al. Voice changes after thyroidectomy without recurrent laryngeal nerve injury. J Am Coll Surg. 2004;199:556–560. 11. Lombardi CP, Raffaeli M, D’Alatri L, et al. Voice and swallowing changes after thyroidectomy in patients without inferior laryngeal nerve injuries. Surgery. 2006;140:1026–1032. 12. McIvor NP, Flint DJ, Gillibrand J, et al. Thyroid surgery and voice-related outcomes. Aust N Z J Surg. 2000;70:179–183. 13. Ryu CH, Ryu J, Ryu YM, et al. Administration of radioactive iodine therapy within 1 year after total thyroidectomy does not affect vocal function. J Nucl Med. 2015;56:1480–1486. 14. Roh J-L, Kim A-Y, Cho MJ. Xerostomia following radiotherapy of the head and neck affects vocal function. J Clin Oncol. 2005;23:3016–3023. 15. Roh J-L, Kim HS, Kim A-Y. The effect of acute xerostomia on vocal function. Arch Otolaryngol Head Neck Surg. 2006;132:542–546. 16. Kiliç MA, Okur E, Yildirim I, et al. Reliability and validity of the Turkish version of the Voice Handicap Index. Kulak Burun Bogaz Ihtis Derg. 2008;18:139–147. 17. Gagel RF, Goepfert H, Callender DL. Changing concepts in the pathogenesis and management of thyroid carcinoma. CA Cancer J Clin. 1996;46:261– 283. 18. Aras T, Kıratlı P, Sarı O, et al. Diferansiye tiroid karsinomlu hastalarda I-131 tedavisinin etkinlig˘i. Genel Tıp Derg. 2001;11:77–80. 19. Alexander C, Bader JB, Schaefer A, et al. Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med. 1998;39:1551–1554. 20. Coover L. Permanent iatrogenic vocal cord paralysis after I-131 therapy: a case report and literature review. Clin Nucl Med. 2000;25:508–510. 21. Synder S. Vocal cord paralysis after radioiodine therapy. J Nucl Med. 1978;19:975–976. 22. Cambil A, Gil E, Ponce C, et al. Bilateral vocal cord paresis after treatment with radioiodine. Rev Esp Med Nucl. 2003;22:97–99. 23. Craswell PW. Vocal cord paresis following radioactive iodine therapy. Br J Clin Pract. 1972;26:571–572. 24. Beshyah S, Al-Fakllouji H, Neave F. Vocal cord palsy: a very rare complication of radioiodine therapy for hyperthyroidism. Ibnosina J Med Biomed Sci. 2009;1:101–106. 25. Isolan-Cury RW, Monte O, Cury AN, et al. Acute effects of radioiodine therapy on the voice and larynx of Basedow-Graves patients. Rev Bras Otorrinolaringol. 2008;74:224–229. 26. Goksel AO, Toplaog˘ lu I. Voice quality assessment via acoustic and spectrographic analysis in patients which had endolaryngeal surgery. Kulak Burun Bogaz Ihtis Derg. 2009;19:253–258. 27. Gonzalez J, Carpi A. Early effects of smoking on the voice: a multidimensional study. Med Sci Monit. 2004;10:649–656. 28. Cox NB, Morrison MD. Acoustic analysis of voice for computerized laryngeal pathology assessment. J Otolaryngol. 1983;12:295–301.
MATERIALS AND METHODS International review board approval was granted by the Okmeydani Training and Research Hospital’s Ethics Committee. This study was conducted at the Okmeydani Training and Research Hospital Ear, Nose and Throat Clinic between March and April 2015. We enrolled 36 patients who underwent total or subtotal thyroidectomy for well-differentiated thyroid carcinoma and planned to have RIA therapy at a dosage of between 1.0 and 2.5 GBq. Twenty-eight patients had underwent total thyroidectomy and eight patients had underwent subtotal thyroidectomy. All patients underwent a complete otolaryngological examination. Patients with upper respiratory tract infections, history of laryngeal surgery or pathology, pulmonary issues, history of head and neck radiotherapy, and reflux or obstructive sleep apnea, and were tobacco users, were excluded. Laryngeal examinations were performed with rigid 70° endoscope (Karl Storz Telecam DX II, Tuttlingen, Germany). The control group consisted of 36 healthy participants. We also compared the results based on gender. All subjects underwent a complete head and neck examination, as well as acoustic and aerodynamic analyses. Voices were recorded using a dynamic microphone placed 15 cm from the lips 2 hours before the treatment and on the 20th day after treatment. Following deep inspiration, subjects were prompted to say the vowel “ah” for as long as they could. This was repeated three times, and the longest recorded time was accepted as the subject’s maximum phonation time (MPT). Additionally, subjects were asked to read a phonetically balanced passage from a famous Turkish story titled “Diyet” for 40 s in a relaxed voice. The Praat software (Version 4.4.13; Boersma and Weenink, University of Amsterdam, Amsterdam, Netherlands) was used for acoustic analysis. The F0, jitter, shimmer, and harmonic-to-noise ratio were determined during acoustic voice analysis. Subjective evaluation was performed using the Voice Handicap Index-10 (VHI-10). The Turkish version of the VHI-10, validated by Kiliç et al,16 consists of 10 questions and is scored between 0 (never) and 4 (always). This questionnaire includes emotional, functional, and physical subscales consisting of four, three, and three questions, respectively.
ARTICLE IN PRESS 2
Journal of Voice, Vol. ■■, No. ■■, 2016
Statistical analysis of the data was conducted using SPSS ver. 17.0 (SPSS IBM USA). After analysis, data were presented using descriptive statistical methods (mean ± standard deviation). Parametric independent sample t-tests were used for comparisons between groups. Results were evaluated using 95% confidence intervals, with the level of significance set as P < 0.05. RESULTS There were 24 (66.6%) papillary thyroid and 12 (33.3%) follicular carcinoma cases. The RIA group consisted of 25 female and 11 male patients with a mean age of 38.7 years (range: 18–63 years). The control group consisted of 24 female and 12 male subjects with a mean age of 36.6 years (range: 20–61 years). Table 1 lists the results of the acoustic and aerodynamic analyses taken before and after RIA therapy, and Table 2 lists the
results of male patients in comparison with the male control group. Table 3 illustrates the female patients in comparison with the female control group. Our results indicated no significant difference between the groups. VHI-10 results before and after RIA therapy were not significant (6.07 ± 3.54 and 5.56 ± 3.23, respectively). In addition, there were no significant differences in the VHI-10 results between the RIA group and the control group. DISCUSSION The incidence of well-differentiated thyroid carcinoma continues to increase worldwide.2,4 The first step to treating this cancer is surgery, involving resection of the tumor and metastatic foci.17 Following surgery, RIA therapy is performed to eliminate remnant thyroid tissue and metastatic foci. This therapy is effective because
TABLE 1. Comparison of Radioactive Iodine Therapy Group and Control Group Parameters MPT F0 Jitter Shimmer HNR Intensity
Before RAI (n = 36) Mean ± SD
After RAI (n = 36) Mean ± SD
Control Group (n = 36) Mean ± SD
P
16.51 ± 2.95 205.45 ± 70.40 0.33 ± 0.19 1.83 ± 0.59 20.69 ± 3.01 70.45 ± 5.40
17.11 ± 2.86 200.50 ± 71.20 0.37 ± 0.23 1.89 ± 0.61 21.63 ± 3.11 69.95 ± 5.60
16.99 ± 2.92 202.52 ± 72.40 0.34 ± 0.21 1.88 ± 0.69 20.99 ± 3.27 69.70 ± 5.51
0.365 0.645 0.622 0.875 0.142 0.432
Abbreviations: F0, fundamental frequency; HNR, harmonic-to-noise ratio; MPT, maximum phonation time; RAI, radioactive iodine therapy; SD, standard deviation.
TABLE 2. Comparison of Results of Male Patients and Male Control Groups Parameters MPT F0 Jitter Shimmer HNR Intensity
Before RAI (n = 11) Mean ± SD
After RAI (n = 11) Mean ± SD
Control Group (n = 12) Mean ± SD
P
17.48 ± 2.87 163.71 ± 42.37 0.32 ± 0.18 1.86 ± 0.47 20.59 ± 2.99 72.01 ± 5.33
16.98 ± 3.01 161.69 ± 46.91 0.36 ± 0.20 1.91 ± 0.59 21.89 ± 3.01 70.21 ± 5.55
17.12 ± 2.81 166.51 ± 44.33 0.35 ± 0.19 1.90 ± 0.68 20.68 ± 3.21 71.34 ± 5.72
0.404 0.561 0.701 0.821 0.199 0.429
Abbreviations: F0, fundamental frequency; HNR, harmonic-to-noise ratio; MPT, maximum phonation time; RAI, radioactive iodine therapy; SD, standard deviation.
TABLE 3. Comparison of Results of Female Patients and Female Control Groups Parameters MPT F0 Jitter Shimmer HNR Intensity
Before RAI (n = 25) Mean ± SD
After RAI (n = 25) Mean ± SD
Control Group (n = 24) Mean ± SD
P
15.98 ± 2.32 221.41 ± 76.46 0.34 ± 0.22 1.82 ± 0.60 21.02 ± 3.23 70.01 ± 5.51
16.23 ± 2.77 219.98 ± 74.90 0.34 ± 0.17 1.88 ± 0.66 20.93 ± 3.17 68.99 ± 5.49
16.71 ± 3.02 225.71 ± 69.11 0.33 ± 0.24 1.87 ± 0.65 21.76 ± 3.14 69.21 ± 5.31
0.693 0.621 0.453 0.757 0.221 0.515
Abbreviations: F0, fundamental frequency; HNR, harmonic-to-noise ratio; MPT, maximum phonation time; RAI, radioactive iodine therapy; SD, standard deviation.
ARTICLE IN PRESS I˙mran Aydog˘du et al
Effects of Radioactive Iodine Ablation Therapy
radioactive iodine has a high affinity to thyroid tissue, and thus can be used to treat well-differentiated thyroid carcinoma. In addition, iodine-131 is economical and user-friendly. Beta radiation emitted from iodine-131 causes damage to follicular cells in a dose-dependent manner. The half-life of iodine-131 is 8 days, which is long enough to treat the carcinoma.18 Following iodine treatment, necrosis can result, leading to fibrosis.6 There are few case reports that mention recurrent laryngeal nerve damage caused by RAI therapy. However, it has been reported that edema from this therapy causes unilateral recurrent laryngeal nerve paralysis.19–24 Of these five cases, two had spontaneous healing within 6 months and two healed within 18 months. None of these reports analyzed voice quality. Although RIA therapy appears to be safe, vocal outcomes should be investigated, especially for patients that are voice professionals. The first study to investigate the effects of RIA therapy on voice quality was performed by Isolan-Cury et al.25 In this study, they performed an acoustic analysis on Graves’ disease patients who underwent RIA therapy. They took recordings before therapy and on days 2, 4, and 18 following therapy. They observed no difference in MPT, F0, and jitter.25 Because voice quality can be affected by a number of variables, patient selection is extremely important. Patients who were below or above a certain age were not included in this study. We also excluded patients with pathologies that can affect voice quality (eg, laryngeal and pulmonary pathologies). MPT reflects prolonged vocalization and continuous speech. It is related to the resistance and force generated at the glottal region.26 F0, the lowest frequency, is the main parameter of the listener’s perception of the speaker’s pitch and is determined primarily by the elasticity, tension, and mass of the vocal folds.27 Jitter and shimmer percentages represent the vibrational action of the glottis, as well as the short-term (period-to-period) irregularity of the pitch and of the peak-to-peak amplitude of the voice, respectively.28 The results from our study revealed no difference in voice quality between the RIA therapy and control groups. CONCLUSIONS RIA therapy had no adverse effect on voice quality objectively and subjectively. Studies with larger patient cohorts and that investigate cepstral analysis of speech will be necessary to completely understand the effects of RIA therapy on voice quality. REFERENCES 1. Jameson JL, Weetman AP. Disorders of the thyroid gland. In: Kasper DL, Fauci AS, Longo DL, et al., eds. Harrison’s Principles of Internal Medicine, 16th Edition. New York: The McGraw Hill Companies; 2005:2014–2126 [Ch 320]. 2. Luster M, Clarke SE, Dietlein M, et al. Guidelines for radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2008;35:1941–1959. 3. Mazzaferri EL, Kloos RT. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin Endocrinol Metab. 2001;86:1447–1463.
3
4. Chen AY, Jemal A, Ward EM. Increasing incidence of differentiated thyroid cancer in the United States, 1988–2005. Cancer. 2009;115:3801–3807. 5. McLeod DSA, Carruthers K, Kevat DAS. Optimal differentiated thyroid cancer management in the elderly. Drugs Aging. 2015;3:283–294. 6. Davies T, Larsen P. Thyrotoxicosis. In: Williams RH, Larsen PR, eds. Williams Textbook of Endocrinology. 10a ed. Philadelphia: Saunders; 2003:374–396. 7. Minni A, Ruoppolo G, Barbaro M, et al. Long-term (12 to 18 months) functional voice assessment to detect voice alterations after thyroidectomy. Eur Rev Med Pharmacol Sci. 2014;18:1704–1708. 8. Hong KH, Kim YK. Phonatory characteristics of patients undergoing thyroidectomy without laryngeal nerve injury. Otolaryngol Head Neck Surg. 1997;117:399–404. 9. Akyıldız S, Ogut F, Akyıldız M, et al. Multivariate analysis of objective voice changes after thyroidectomy without laryngeal nerve injury. Arch Otolaryngol Head Neck Surg. 2008;134:596–602. 10. Sinagra DL, Montesinos MR, Tacchi VA, et al. Voice changes after thyroidectomy without recurrent laryngeal nerve injury. J Am Coll Surg. 2004;199:556–560. 11. Lombardi CP, Raffaeli M, D’Alatri L, et al. Voice and swallowing changes after thyroidectomy in patients without inferior laryngeal nerve injuries. Surgery. 2006;140:1026–1032. 12. McIvor NP, Flint DJ, Gillibrand J, et al. Thyroid surgery and voice-related outcomes. Aust N Z J Surg. 2000;70:179–183. 13. Ryu CH, Ryu J, Ryu YM, et al. Administration of radioactive iodine therapy within 1 year after total thyroidectomy does not affect vocal function. J Nucl Med. 2015;56:1480–1486. 14. Roh J-L, Kim A-Y, Cho MJ. Xerostomia following radiotherapy of the head and neck affects vocal function. J Clin Oncol. 2005;23:3016–3023. 15. Roh J-L, Kim HS, Kim A-Y. The effect of acute xerostomia on vocal function. Arch Otolaryngol Head Neck Surg. 2006;132:542–546. 16. Kiliç MA, Okur E, Yildirim I, et al. Reliability and validity of the Turkish version of the Voice Handicap Index. Kulak Burun Bogaz Ihtis Derg. 2008;18:139–147. 17. Gagel RF, Goepfert H, Callender DL. Changing concepts in the pathogenesis and management of thyroid carcinoma. CA Cancer J Clin. 1996;46:261– 283. 18. Aras T, Kıratlı P, Sarı O, et al. Diferansiye tiroid karsinomlu hastalarda I-131 tedavisinin etkinlig˘i. Genel Tıp Derg. 2001;11:77–80. 19. Alexander C, Bader JB, Schaefer A, et al. Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. J Nucl Med. 1998;39:1551–1554. 20. Coover L. Permanent iatrogenic vocal cord paralysis after I-131 therapy: a case report and literature review. Clin Nucl Med. 2000;25:508–510. 21. Synder S. Vocal cord paralysis after radioiodine therapy. J Nucl Med. 1978;19:975–976. 22. Cambil A, Gil E, Ponce C, et al. Bilateral vocal cord paresis after treatment with radioiodine. Rev Esp Med Nucl. 2003;22:97–99. 23. Craswell PW. Vocal cord paresis following radioactive iodine therapy. Br J Clin Pract. 1972;26:571–572. 24. Beshyah S, Al-Fakllouji H, Neave F. Vocal cord palsy: a very rare complication of radioiodine therapy for hyperthyroidism. Ibnosina J Med Biomed Sci. 2009;1:101–106. 25. Isolan-Cury RW, Monte O, Cury AN, et al. Acute effects of radioiodine therapy on the voice and larynx of Basedow-Graves patients. Rev Bras Otorrinolaringol. 2008;74:224–229. 26. Goksel AO, Toplaog˘ lu I. Voice quality assessment via acoustic and spectrographic analysis in patients which had endolaryngeal surgery. Kulak Burun Bogaz Ihtis Derg. 2009;19:253–258. 27. Gonzalez J, Carpi A. Early effects of smoking on the voice: a multidimensional study. Med Sci Monit. 2004;10:649–656. 28. Cox NB, Morrison MD. Acoustic analysis of voice for computerized laryngeal pathology assessment. J Otolaryngol. 1983;12:295–301.