|Year : 2019 | Volume
| Issue : 3 | Page : 676-680
Incidence of thyroid cancer and medical cost among patients with newly diagnosed thyroid nodules in Korea: A retrospective cohort study using nationwide data
Min Kyung Hyun1, Jong Hee Kim2, Jin Won Kwon3
1 Department of Preventive Medicine, College of Korean Medicine, Dongguk University, Gyeongju-si, Republic of Korea
2 National Health Insurance Service, Wonjoo, Republic of Korea
3 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea
|Date of Web Publication||29-May-2019|
Prof. Jin Won Kwon
80 Daehak-ro, Buk-gu, Daegu 41566
Republic of Korea
Source of Support: None, Conflict of Interest: None
Aims: The frequency of newly diagnosed thyroid nodules is increasing in South Korea. However, few studies have investigated the incidence of thyroid cancer in patients with thyroid nodules using national data. Therefore, this study was conducted to investigate the incidence of thyroid cancer and medical costs among patients newly diagnosed with thyroid nodules in South Korea.
Settings and Design: This was a retrospective cohort study.
Subjects and Methods: We analyzed the national health claim database, which includes all hospital records and covers almost every population managed by the National Health Insurance System. We selected patients aged 20–120 years with new thyroid nodules in 2008 using the International Classification of Diseases, Tenth Edition codes. We followed the selected cases for at least 2 years after thyroid nodule diagnosis to investigate cancer development and medical costs.
Statistical Analysis Used: Frequency analysis was used.
Results: We identified 283,844 eligible patients with thyroid nodules. Their mean age was 48 ± 13.2, and 234,388 (82.58%) cases were female. During the median follow-up of 2.4 years, 21,538 (7.6%) patients were diagnosed with thyroid cancer, and 93.5% of them underwent treatment such as thyroidectomy, chemotherapy, or radiotherapy. The average medical cost was 3,996,391 KRW after diagnosis of thyroid cancer.
Conclusions: Here, national representative statistics regarding the incidence and medical costs of thyroid nodule and thyroid cancer are presented. The information provided herein will improve understanding of the natural course of thyroid nodules in Asians. Further study is needed to identify the risk factors of thyroid cancer in patients with thyroid nodules.
Keywords: Health-care costs, incidence, retrospective cohort studies, thyroid cancer, thyroid nodule
|How to cite this article:|
Hyun MK, Kim JH, Kwon JW. Incidence of thyroid cancer and medical cost among patients with newly diagnosed thyroid nodules in Korea: A retrospective cohort study using nationwide data. J Can Res Ther 2019;15:676-80
|How to cite this URL:|
Hyun MK, Kim JH, Kwon JW. Incidence of thyroid cancer and medical cost among patients with newly diagnosed thyroid nodules in Korea: A retrospective cohort study using nationwide data. J Can Res Ther [serial online] 2019 [cited 2021 Dec 4];15:676-80. Available from: https://www.cancerjournal.net/text.asp?2019/15/3/676/204895
| > Introduction|| |
Recently, the incidence of thyroid cancer has increased rapidly worldwide. According to statistics disclosed in 2013 by the Korea Central Cancer Registry, National Cancer Center, thyroid cancer had the highest incidence rate of 18.9%. In females, the level can reach 30.5%, while in males, it is 7.4%. According to trends in the age-standardized thyroid cancer incidence rates from 1999 to 2013, the annual rate of change is 21.2%, being 23.4% for males and 20.9% for females. This is the highest increase in incidence among all types of cancers. This gradual increasing phenomenon of thyroid cancer has not just occurred in South Korea but has been a global phenomenon over the last 30 years. In Australia, the incidence of thyroid cancer increased by 13.8% for females from 2000 to 2007, while in the United States, the incidence increased by 7% from 1997 to 2009. In Canada, the average annual increase rate is 3.5% for males and 3.2% for females from 1970/72 to 1994/96. In 2012, the age-standardized thyroid cancer incidence rates were 20.0% (ranked fourth) in the United States and 6.5% (ranked ninth) in Japan, while England was not in the top 10 among all types of cancers.
The rapid increase in thyroid cancer has been attributed to increased occurrence of small papillary cancers. Indeed, it has been confirmed that small papillary cancers with a size of 0–1.0 cm contribute to the total increase of thyroid cancer incidence. In addition, it has been reported that less than half of thyroid cancers and thyroidectomies were diagnosed by screening and chance identification., Thyroid nodules are found in 4%–7% of the general population and 5%–10% of these nodules are diagnosed as malignant.,, However, few recent studies have investigated the incidence of thyroid cancer among patients with newly diagnosed thyroid nodules using ultrasonography for thyroid cancer screening. Therefore, in this study, we investigated the incidence of thyroid cancer and medical costs among patients with newly diagnosed thyroid nodules in a retrospective cohort using national representative data from Korea.
| > Subjects and Methods|| |
We used a nationwide insurance claim database from 2006 to 2010 provided by the Health Insurance Review and Assessment Service. Korea has a unique national health insurance system that covers the entire population including 97% health insurance and 3% medical aid. This database was established for reimbursement purposes, but it has previously been used for health-related studies. This study was approved by the Institutional Review Board at the National Evidence-based Collaborating Agency.
Inclusion and exclusion criteria for patients
We selected 485,223 patients aged 20–120 years with thyroid nodules codes (D34, E041, and E042), and an index date for each patient was defined by the first diagnosis with thyroid nodule in 2008. New patients were identified after excluding those who were previously reported to have thyroid cancer (C73), other organ cancer (C), or thyroid nodule before the index date. Thyroid nodule was defined based on diagnosis code or operation code (C8591, C8592) of the fine-needle aspiration (FNA) cytology test. Thyroid cancer was defined using the diagnosis code for thyroidectomy (P4551, P4552, P4553, P4554, and P4561), chemotherapy, or radiation therapy. A total of 283,844 patients were selected in 2008 based on our criteria, and we followed them for at least 2 years after diagnosis of thyroid nodule.
Definition of outcome and variables
We summarized the patient demographics, clinical information obtained using the Charlson comorbidity index (CCI), type of medical facility, and department. The CCI score was calculated based on the 19 clinical conditions defined by Charlson and subsequently divided into four different groups based on scores of 0, 1, 2, and ≥3., The medical facilities were categorized into tertiary hospitals, general hospitals, hospitals, and clinics, and the medical departments were classified into four categories, internal medicine, surgery, orthopedics, and others. To investigate the incidence of thyroid nodule per 100,000 Koreans, we applied the Korean population in 2008 as a denominator. Cancer incidence rate was also investigated during follow-up periods.
We also analyzed the incidence rate and time from nodule to cancer incidence, treatment rate of thyroid cancer, and medical costs. The medical costs per patient were calculated based on outpatient treatment and hospitalization fees in response to diagnosis of thyroid nodule before diagnosis with thyroid cancer. We also calculated the medical costs caused by thyroid cancer. Costs included direct medical costs such as hospital admissions, outpatient visits, emergency room visits, medications, and surgical operations. It consisted of reimbursement by the national health insurance and legal out-of-pocket expenses from the patient, in which extreme costs of more than 1% were excluded because they were considered outliers that lead to bias in cost estimation.
Frequencies and percentages are presented for gender, age, type of medical facility, and medical department. The thyroid cancer incidence rates among patients with thyroid nodules were calculated. All data manipulation and statistical analyses were conducted using SAS 9.1.3 (SAS Institute, Cary, NC, USA).
| > Results|| |
Characteristics of patients with thyroid nodule
The characteristics of 283,844 patients, including gender, age, and type of medical facility and medical department of the sample population, are shown in [Table 1]. The frequency of thyroid nodule patients was four times higher in females than in males (female 82.58%, male 17.42%). The mean age (standard deviation) was 48 years (13.2), with the highest proportion being 30–49. Clinics had the highest frequency, followed by general hospitals. The internal department showed the highest frequency among medical departments [Table 1].
|Table 1: Characteristics of new patients newly diagnosed with thyroid nodules in 2008|
Click here to view
Incidence rate of new thyroid nodules
There were 283,844 patients with thyroid nodule first diagnosed in 2008, which was estimated to be a new occurrence rate of 775/100,000 patients based on the estimated population provided by the Korean Statistics Office [Figure 1].
Incidence rate and treatment pattern of thyroid cancer from new thyroid nodule
Among 283,844 patients, 21,538 (7.6%) were diagnosed with thyroid cancer in 2008–2010. Within 1 year of detection of a new thyroid nodule, 18,849 (6.6%) patients were diagnosed with thyroid cancer [Table 2]. Furthermore, 92% of patients with thyroid cancer underwent thyroidectomy, 6.5% were not treated, and 1.5% underwent chemotherapy [Figure 2].
|Table 2: Thyroid cancer development in patients with new thyroid nodules over 3 years|
Click here to view
Medical costs of thyroid nodule and thyroid cancer
Medical cost analysis was based on 21,267 cases after exclusion of the upper 1% in the cost distribution. The average annual medical costs were 1,366,577 KRW per patient with thyroid nodule before the diagnosis of thyroid cancer. This cost increased to 3,996,371 KRW per patient after diagnosis with thyroid cancer, which meant that medical costs were 2.9 times higher after the diagnosis [Figure 3].
|Figure 3: Pre-post comparison of average medical costs when patients with newly diagnosed thyroid nodules were diagnosed with thyroid cancer. (A) After diagnosis with thyroid nodule but before diagnosis with thyroid cancer. (B) After diagnosis with thyroid cancer. Note: Patients (n = 21,267): Patients with newly diagnosed thyroid nodules that were also diagnosed with thyroid cancer, excluding those accounting for the top 1% of the medical cost|
Click here to view
| > Discussion|| |
This is the first study to compare the incidence of thyroid nodules and thyroid cancer and medical costs among patients with newly diagnosed thyroid nodules using nationwide insurance claim data from 2006 to 2010 in Korea. In our study, 775/100,000 (0.8%) adults were identified as having thyroid nodules, and they spent an average of KW 1,366,577 on treatment per year. Thyroid nodules are very common in adults, with about 19%–68% of all adults having at least one thyroid nodule., Accordingly, screening of the entire population by ultrasonography would be a waste of money, especially for countries with nationwide insurance such as South Korea. This is because there is insufficient evidence to determine if ultrasonographic screening to detect thyroid nodule is effective or not at reducing the morbidity or mortality associated with thyroid cancer. Furthermore, detection of thyroid nodules may increase anxiety and costs even though there is little possibility of cancer development. Indeed, it has been suggested that use of ultrasonography to detect thyroid nodules be suspended until a thorough cost/benefit analysis is conducted. Various investigations of the natural history of thyroid nodules are needed to avoid the unnecessary anxiety associated with their discovery and define their correlation with the risk of mortality due to thyroid cancer.
Based on demographics, the percentage of gender and mean age of patients with thyroid nodules in this study were similar with those of several previous studies that showed higher rates in women (80%) than men and a mean patient age of about 50 years.,,
In general, 5%–15% of nodules are diagnosed as malignant in the general population;,,,, therefore, the rate of 7.6% observed in this study is reasonable. Some small studies have reported various malignant rates of thyroid nodule in hospital settings. For example, the malignant rate was 42.7% among 1310 nodules (1254 patients) of asymptomatic patients in one South Korean hospital  and 1.7% among 700 nodules in another South Korean study. Moreover, these rates were 17.8% patients among ninety patients in Iran, and 26.4% in a core needle biopsy group and 24.7% in a diagnostic surgery group in Italy. These studies were relatively higher incidence rates of thyroid cancer. These discrepancies may have been due to differences in populations and settings. In small studies, most patients likely visited hospitals and clinics because of symptoms and self-detection of nodules.
It has been debated whether papillary carcinoma with a size of <0.5 cm should be treated because it has a good prognosis and low mortality rate. Recent guidelines have stated that it should not be subjected to FNA to prevent unnecessary operation.,, Although this study was limited in that we did not know the size and severity of thyroid cancer, 92% of patients with thyroid cancer underwent thyroidectomy and 3,996,371 KRW per patient was paid by thyroid cancer patients after being diagnosed with thyroid nodules. Conversely, the proportion of individuals undergoing thyroidectomy to treat thyroid cancer was 10.4% at the end of 2012, and they paid $416 million in 2006 in the United States., However, it is not clear how much benefit is provided by surgical intervention for low-risk thyroid cancers because thyroidectomy may cause surgery-related complication, such as hypoparathyroidism (or hypocalcemia), injury to the recurrent laryngeal nerve, and bleeding.,,
This study provides the first results of the incidence rate of thyroid cancer from new thyroid nodules based on a nationwide database. The most important limitation of this study was that the size and number of thyroid nodules and the risk of thyroid cancer were not determined based on the nationwide insurance claim database but was instead based on secondary data. Moreover, it is important to note that no size information was available when interpreting the results because large thyroid nodules may affect the prevalence and posttest probability of malignancy.
| > Conclusions|| |
The incidence of thyroid cancer was still high, and the amount of medical costs associated with it cannot be overlooked. Therefore, follow-up studies investigating the incidence and natural history of thyroid nodules in Korea are needed. Moreover, further study is needed to identify the population at risk of having high mortality due to thyroid cancer among patients with thyroid nodules to enable more effective screening.
Financial support and sponsorship
This study was funded by the National Evidence-based Healthcare Collaborating Agency in the Republic of Korea (project no. NM 2011-04).
Conflicts of interest
There are no conflicts of interest.
| > References|| |
National Cancer Information Center. National cancer statistics in Korea in 2013; 2015.
Pellegriti G, Frasca F, Regalbuto C, Squatrito S, Vigneri R. Worldwide increasing incidence of thyroid cancer: Update on epidemiology and risk factors. J Cancer Epidemiol 2013;2013:965212.
Nguyen QT, Lee EJ, Huang MG, Park YI, Khullar A, Plodkowski RA. Diagnosis and treatment of patients with thyroid cancer. Am Health Drug Benefits 2015;8:30-40.
Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 2006;295:2164-7.
Davies L, Ouellette M, Hunter M, Welch HG. The increasing incidence of small thyroid cancers: Where are the cases coming from? Laryngoscope 2010;120:2446-51.
Tufano RP, Noureldine SI, Angelos P. Incidental thyroid nodules and thyroid cancer: Considerations before determining management. JAMA Otolaryngol Head Neck Surg 2015;141:566-72.
Ugurluoglu C, Dobur F, Karabagli P, Celik ZE. Fine needle aspiration biopsy of thyroid nodules: Cytologic and histopathologic correlation of 1096 patients. Int J Clin Exp Pathol 2015;8:14800-5.
Ugurlu MU, Uprak K, Akpinar IN, Attaallah W, Yegen C, Gulluoglu BM. Radiofrequency ablation of benign symptomatic thyroid nodules: Prospective safety and efficacy study. World J Surg 2015;39:961-8.
Tan GH, Gharib H. Thyroid incidentalomas: Management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997;126:226-31.
Kim DS. Introduction: Health of the health care system in Korea. Soc Work Public Health 2010;25:127-41.
Lee CH, Hyun MK, Jang EJ, Lee NR, Kim K, Yim JJ. Inhaled corticosteroid use and risks of lung cancer and laryngeal cancer. Respir Med 2013;107:1222-33.
Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol 2004;57:1288-94.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 1987;40:373-83.
Statistics Korea. Korean population and household in 2008; 2008.
Russ G, Leboulleux S, Leenhardt L, Hegedüs L. Thyroid incidentalomas: Epidemiology, risk stratification with ultrasound and workup. Eur Thyroid J 2014;3:154-63.
Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al.
2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2016;26:1-133.
Shin S, Park SE, Kim SY, Hyun MK, Kim SW, Kwon JW, et al.
Effectiveness of ultrasonographic screening for thyroid cancer: Round-table conference in the National Evidence- based Healthcare Collaborating Agency (NECA) in conjunction with the Korean Thyroid Association. Asian Pac J Cancer Prev 2014;15:5107-10.
Cronan JJ. Thyroid nodules: Is it time to turn off the US machines? Radiology 2008;247:602-4.
Medici M, Liu X, Kwong N, Angell TE, Marqusee E, Kim MI, et al.
Long- versus short-interval follow-up of cytologically benign thyroid nodules: A prospective cohort study. BMC Med 2016;14:11.
Singh Ospina N, Maraka S, Espinosa DeYcaza A, O'Keeffe D, Brito JP, Gionfriddo MR, et al.
Diagnostic accuracy of thyroid nodule growth to predict malignancy in thyroid nodules with benign cytology: Systematic review and meta-analysis. Clin Endocrinol (Oxf) 2016;85:122-31.
Remonti LR, Kramer CK, Leitão CB, Pinto LC, Gross JL. Thyroid ultrasound features and risk of carcinoma: A systematic review and meta-analysis of observational studies. Thyroid 2015;25:538-50.
Singer PA, Cooper DS, Daniels GH, Ladenson PW, Greenspan FS, Levy EG, et al.
Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association. Arch Intern Med 1996;156:2165-72.
Hwang SH, Kim EK, Moon HJ, Yoon JH, Kwak JY. Risk of thyroid cancer in euthyroid asymptomatic patients with thyroid nodules with an emphasis on family history of thyroid cancer. Korean J Radiol 2016;17:255-63.
Choi YJ, Jung I, Min SJ, Kim HJ, Kim JH, Kim S, et al.
Thyroid nodule with benign cytology: Is clinical follow-up enough? PLoS One 2013;8:e63834.
Akhavan A, Jafari SM, Khosravi MH, Khajehpour H, Karimi-Sari H. Reliability of fine-needle aspiration and ultrasound-based characteristics of thyroid nodules for diagnosing malignancy in Iranian patients. Diagn Cytopathol 2016;44:269-73.
Trimboli P, Nasrollah N, Amendola S, Crescenzi A, Guidobaldi L, Chiesa C, et al.
A cost analysis of thyroid core needle biopsy vs. diagnostic surgery. Gland Surg 2015;4:307-11.
Ho TW, Shaheen AA, Dixon E, Harvey A. Utilization of thyroidectomy for benign disease in the United States: A 15-year population-based study. Am J Surg 2011;201:570-4.
Selberherr A, Scheuba C, Riss P, Niederle B. Postoperative hypoparathyroidism after thyroidectomy: Efficient and cost-effective diagnosis and treatment. Surgery 2015;157:349-53.
Nixon I. The surgical approach to differentiated thyroid cancer. F1000Res 2015;4. pii: F1000 Rev-1366.
Shin JJ, Caragacianu D, Randolph GW. Impact of thyroid nodule size on prevalence and post-test probability of malignancy: A systematic review. Laryngoscope 2015;125:263-72.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
|This article has been cited by|
||Thyroid cancer and its associated factors: A population-based case-control study
| ||Mohammad Taher Parad, Mohammad Fararouei, Ali Reza Mirahmadizadeh, Sima Afrashteh |
| ||International Journal of Cancer. 2021; 149(3): 514 |
|[Pubmed] | [DOI]|
||Impact of drug formulation on outcomes of pharmaceutical poisoning in children aged 7 years or younger
| ||Yura Ko, Woochan Jeon, Yoo Jin Choi, Heewon Yang, Jisook Lee |
| ||Medicine. 2021; 100(40): e27485 |
|[Pubmed] | [DOI]|
||Differentiated Thyroid Cancer: A Health Economic Review
| ||Klaas Van Den Heede, Neil S. Tolley, Aimee N. Di Marco, Fausto F. Palazzo |
| ||Cancers. 2021; 13(9): 2253 |
|[Pubmed] | [DOI]|