The Current Status of Hyperthyroidism in Korea
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Thyroid hormones increase tissue thermogenesis and the basal metabolic rate, and reduce serum cholesterol levels and systemic vascular resistance [1]. Hyperthyroidism occurs due to excessive synthesis and secretion of thyroid hormones by the thyroid [2]. Since hyperthyroidism is a potential risk factor for weight loss, cardiovascular disease, arrhythmia, osteoporosis, fragility fractures, and neuropsychiatric disease, it is of the utmost importance to understand the current status of this condition [3].
The prevalence and incidence of thyroid dysfunction vary across populations and can be influenced by several factors such as age, sex, ethnicity, and iodine status [4-7]. The prevalence of overt hyperthyroidism has been reported to be 0.5% to 0.8% in Europe and 0.5% in the United States [3,8]. Several studies have reported the prevalence and incidence of hyperthyroidism in Korea [9-11].
A recent study using the National Health Insurance (NHI) database after excluding subjects with thyroid cancer reported that the prevalence of hyperthyroidism in patients undergoing treatment was 2.76 per 1,000 population in Korea in 2015 with a noteworthy sex disparity shown by rates of 1.79 per 1,000 population among men and 3.74 per 1,000 population among women [11]. The prevalence of hyperthyroidism reported in previous Korean studies was similar to the rates in other countries [3,8]. In a study published in 2013 using the Health Insurance Review & Assessment Service (HIRA) database, the prevalence of hyperthyroidism was 3.40 per 1,000 population (2.09 among men and 4.70 among women) [10]. The study using Korea National Health and Nutrition Examination Survey VI reported that the prevalence of overt and subclinical hyperthyroidism was 0.54% and 2.98%, respectively, using the reference interval of serum thyroid-stimulating hormone in the Korean reference population [9].
A recent study using the NHI database found that the number of incident cases of hyperthyroidism steadily increased from 2006 to 2012, and then decreased through 2015 [11]. The incidence of hyperthyroidism in patients undergoing treatment was 0.55 per 1,000 population in Korea in 2015 [11]. In the study published in 2013 using HIRA database, the incidence of hyperthyroidism was 0.72 per 1,000 population (0.40 among men and 1.03 among women) [10].
Ahn et al. [12] reported the current status of hyperthyroidism in Korea from 2003 to 2018 using nationwide population-based data from the NHI. The authors evaluated the prevalence and the changes in annual age-standardized incidence during the study period. In Korea, hyperthyroidism occurred about 2.5 times more in women than in men. As of 2018, the prevalence of hyperthyroidism was 3.04 per 1,000 population, and the agestandardized prevalence was 2.48 per 1,000 population. The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively.
In addition, Ahn et al. [12] evaluated the treatment of choice for hyperthyroidism and its changes during the study period. In Korea, antithyroid drugs were preferred as the first-line treatment for hyperthyroidism. The percentage of patients who received antithyroid drug treatment did not change substantially throughout the entire study period, remaining at approximately 93.7% of all hyperthyroidism patients. Meanwhile, the annual proportions of ablation therapy decreased from 7.68% in 2008 to 4.56% in 2018. Specifically, the average proportions of radioactive iodine treatment were 5.68%±0.31% from 2003 to 2008, which then gradually decreased from 6.0% in 2008 to 2.6% in 2018. However, the proportions of patients who underwent surgery showed no significant difference over time, from 1.43% in 2003 to 1.95% in 2018.
Methimazole has recently emerged as the most frequently prescribed antithyroid drug, out of three types of antithyroid drugs [11]. Prior to 2009, propylthiouracil held the position of the most commonly used drug for patients with hyperthyroidism, but in 2010, methimazole overtook propylthiouracil [11]. The Food and Drug Administration issued a safety alert regarding the use of propylthiouracil in 2009, because propylthiouracil can lead to fulminant hepatic necrosis that could be fatal [13- 15]. In light of these safety concerns, the American Thyroid Association and American Association of Clinical Endocrinologists guidelines and the Korean Thyroid Association guidelines recommended using methimazole to treat hyperthyrodism, except within the first trimester of pregnancy and for patients in thyrotoxic crisis [15,16]. For these reasons, physicians’ prescription trends have shifted, and methimazole became the most frequently prescribed antithyroid drug in 2015.
Nonetheless, antithyroid drugs are associated with several complications including agranulocytosis, acute pancreatitis, and hepatitis. It is important to understand the clinical characteristics and the risk factors of these antithyroid drug related complications. Ahn et al. [12] reported that the overall incidence rates of agranulocytosis within 1 year after initiating antithyroid drugs were 0.08% and 0.15% in male and female among hyperthyroidism patients, respectively. A previous multicenter study including Korean patients with antithyroid drug related agranulocytosis diagnosed between 1997 and 2014 reported that the majority of incidents occurred in the early treatment period specifically, the initial 3-month period of treatment accounted for 75.9% of cases of agranulocytosis [17]. The mean age of the patients (11 males, 43 females) was 38.2±14.9 years. Forty-eight patients (88.9%) with agranulocytosis had fever and sore throat on initial presentation.
The overall incidence of acute hepatitis within 90 days after initiating antithyroid drug was found to be 0.53% in both sexes [12]. The peak-incidence age was 20 to 29 years old, and the incidence of this complication gradually decreased with age in both sexes. The overall incidence rates of acute pancreatitis occurring within 90 days after initiating antithyroid drugs were 0.08% in men and 0.05% in women, respectively [12]. Further studies evaluating the clinical characteristics and risk factors for these drug related complications are needed.
Hyperthyroidism is associated with several comorbidities including atrial fibrillation or flutter, heart failure, osteopenia or osteoporosis, and fractures [1,2,12,16]. Ahn et al. [12] reported that hyperthyroid patients may have a higher risk of these comorbidities at a younger age than the general population. The prevalence of atrial fibrillation or flutter was 5.93% and 3.84% in men and women, respectively [12]. The prevalence of heart failure was 3.21% in men and 2.86% in women. The prevalence of osteopenia or osteoporosis was 5.59% in men and 18.18% in women. The prevalence of fracture was 9.11% in men and 11.81% in women.
In conclusion, understanding the current status of hyperthyroidism is important for its proper diagnosis and management, because hyperthyroid patients may face a higher risk of several comorbidities including atrial fibrillation or flutter, heart failure, osteopenia or osteoporosis, and fractures at a younger age than the general population. As of 2018, in Korea, the prevalence of hyperthyroidism was 3.04 per 1,000 population, with an age-standardized prevalence of 2.48 per 1,000 population. Hyperthyroidism was about 2.5 times more prevalent in women than in men. The first-line treatment for hyperthyroidism consisted of antithyroid drugs, with methimazole being the most frequently prescribed option. However, it is crucial to consider that antithyroid drugs are associated with several complications, including agranulocytosis, acute pancreatitis, and hepatitis.
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CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.