Thyroidism is a relatively common disease but its reported incidence varies, being dependent upon the research subject groups and the diagnostic criteria used. The prevalences of overt hyperthyroidism or overt hypothyroidism and subclinical thyrotoxicosis have been reported to be 5%, 5% and 1% respectively^1–7). Subclinical hypothyroidism has been reported to have prevalences from 4–10% in the general population to 7–26% in the geriatric population^8–11). Such thyroid dysfunctions cause changes in the lipoprotein metabolism. It is generally accepted that overt hypothyroidism accelerates the progress of cardiovascular diseases by increasing the total cholesterol and low density lipoprotein cholesterol, LDL-C, levels. Also, hypercholesterolemia caused by hypothyroidism is known to be a reversible phenomenon that can respond to thyroid hormone therapy^12–15). However, many contradictory results have been reported on the relationship between subclinical hypothyroidism and abnormal plasma lipids. As a result of comparing patients with subclinical hypothyroidism and normal controls, no significant difference was found in plasma lipids, nor did thyroid hormone therapy cause a significant difference in this respect^{2, 15–18)}. Whereas recent studies have reported that total cholesterol and low-density lipoprotein cholesterol are more elevated in subclinical hypothyroidism than in normal controls^19–22). These are crucial risk factors and are the basis of thyroid hormone therapy. However, since many studies on the relationship between subclinical hypothyroidism and hyperlipidemia have been performed using selected groups of subjects of 55 years or older, they do not represent the subject group of interest in terms of cardiovascular diseases prevention²³⁾. Thus, we examined the prevalence of thyroid dysfunctions in Korea, and used a large number of subjects covering a wide age range. These subjects had visited hospital for medical check-ups.

The determination of the prevalence of thyroidism in a population can produce different results, according to the subject groups or diagnostic criteria chosen. In this study, the average prevalence of overt hyperthyroidism in Korea for all age levels was 5/1,000 (3.5/1,000 in males and 8.0/1,000 in females), and was highest in the 60’s age group. In 1997, in the English Whickham survey²⁾, the prevalence of thyroidism, including past medical history, was higher than that of the present survey with 19 female patients per 1,000 female patients, and 1.6 male patients per 1,000 male patients, and though it also found a higher prevalence in females, no association was found with age. In a Colorado study³⁾, thyrotoxicosis showed a prevalence of 0.1%, which is lower than that found in the present study, and a study in Spain¹¹⁾ also showed a prevalence rate of 0.2%, which again is lower than that found by the present study. We found that the average prevalence of overt hypothyroidism in Korea is 1.6/1,000 (0.6 males and 3.6 females). In terms of age, those in their 70’s showed the highest with 9.4/1,000, and this was higher than that found in the Whickham or Colorado studies, with 1.9% and 0.4%, respectively. In the present study, the average prevalence of subclinical thyrotoxicosis in Korea was found to be 6.4/1,000 (4.9 in males and 9.4 in females), which is much higher than the prevalences of 0.09% in males, and 0.46% in females found in Norway⁶⁾, but lower than the 2.1% found in Colorado, and much lower than the 7.3% in males and the 5.9% in females found in Germany⁷⁾. In the present study, the average prevalence of subclinical hypothyrodism was 5.7/1,000 (3 in males and 10.9 in females), and the condition was found to be significantly more likely to occur in females. Age related prevalence showed a tendency to increase, and the 60’s showed the highest prevalence at 11.6/1,000. In Norwegian study⁶⁾, the prevalence of subclinical hypothyroidism was 0.37% in males, and 0.9% in females, and the prevalence was highest in the 60’s, which agrees with the results or the present study⁴⁾. In the Whickham survey, the prevalence of subclinical hypothyroidism was three times higher in females than in men.

The Colorado, Danish⁵⁾ and Spain Spanish surveys have showed higher prevalences of subclinical hypothyroidism respectively (9%, 7.2% and 5.6%). In view of these results, the prevalence of subclinical hypothyroidism in Korea seems lower than in other countries, but significantly higher in females than in man and is increase with age. Compared to the study of Jung et al.³⁸⁾, who studied the prevalence rates in a population that had received medical check-ups, the present study shows a lower prevalence of thyroid dysfunction. The reasons for this difference are probably due to the different age profiles of the subject groups, and the different diagnostic criteria and tests used to diagnose thyroid dysfunction. In other words, the present study showed that the 30’s predominate, and that the average age of this study was 41.5, whereas though the study by Jung et al. did not state the average age the 40’s predominated. In addition, Jung et al. measured the concentrations of T3, T4, and TSH whereas we measured the concentrations of FT4 and TSH to evaluate the thyroid function. In addition, the concentration of TSH for diagnosing thyrotoxicosis was applied differently, with 0.25 uIU/mL in the present study, and 0.30 uIU/mL in the study by Jung et al. However, the fact that the thyroid dysfunction was more commonly observed in women than in men, and that hypothyroidism is more commonly observed as age increases, are common findings. The limitation of the present study is that patients who were receiving treatment for thyroid dysfunction could have been included in the normal group due to the lack of an investigation into the medical and treatment histories of subjects with respect to thyroidism. To counterbalance the effect of such a limitation, our study involved over 60,000 subjects, which allowed cardiovascular risk factors such as, blood pressures, blood sugar, level of obesity, dyslipidemia, lipoprotein (a), and hsCRP to be analyzed. Thyroid hormones and serum lipids are known to be closely^{14, 24, 25)}. Moreover, it has been verified that overt hypothyroidism can cause cardiovascular diseases and arteriosclerosis by increasing the total cholesterol and low-density lipoprotein cholesterol. Its mechanism has been attributed to the fact that the concentration of low-density lipoprotein cholesterol receptors falls in fibroblasts, the liver and in other tissues that the diseased thyroid cannot absorb low-density lipoprotein cholesterol as well as the normal thyroid. Thus, this material accumulates in the blood. With thyroid hormone therapy, adverse effects can be controlled and total cholesterol and low-density lipoprotein cholesterol values can be decreased²⁶⁾. However, there is no clear evidence that subclinical hypothyroidism can cause cardiovascular disease, as results are contradictory^{20–23, 26)} Recently, several studies have found than an increase in total cholesterol and low-density lipoprotein cholesterol levels are a primary cause of arteriosclerosis and cardiovascular diseases in subclinical hypothyroidism^{19, 27, 28)}. Various mechanisms are involved in the relationships between subclinical hypothyroidism arteriosclerosis and cardiovascular diseases. Thyroid auto-immunity is one such mechanism, which is related to cardiovascular diseases. This is an abnormal immunoreactivity, which is related to vascular injuries mediated by immune-complex^{29, 31)}.

In a Rotterdam study¹⁹⁾, the incidence of arteriosclerosis or hyperlipidemia was found to be higher in subclinical hypothyroidism in the presence of antibodies for thyroid peroxidase. Moreover, the low-density lipoprotein cholesterol level was found to fall by approximately 12% on thyroid hormone therapy¹⁹⁾.

When subclinical hypothyroidism patients, who show hyperlipidemia, receive thyroid hormone therapy, it causes the total cholesterol and low-density lipoprotein cholesterol to drop, and can decrease the incidence of cardiovascular diseases. In addition, it has been reported that this occurs more so when thyroid auto-antibodies are present^{19–21, 32)}. On the other hand, thyroid hormone therapy causes serum lipid response to changes with TSH level¹⁷⁾. It has also been reported that when TSH>10 mU/L, total cholesterol and low-density lipoprotein cholesterol decrease, but when TSH<10 mU/L, there is no effec^{15, 17, 26)}. In other words, the higher the severity of hypothyroidism, the larger the effects of the thyroid hormone therapy upon hyperlipidemia, when thyroid autoantibodies are benign. There have not been many systematic studies on the relationship between thyroid function and high-density lipoprotein cholesterol, and studies have shown different results, though many have been reported as statistically insignificant. Some studies have reported that the high-density lipoprotein cholesterol level reduces in thyrotoxicosis and increases in hypothyroidism^{24, 25)}. Although Carantoni et al.³³⁾ reported that the high-density lipoprotein cholesterol level decreases with hypothyroidism and contributes to the risk of cardiovascular diseases. In the present study, the total cholesterol was lower in overt and subclinical thyrotoxicosis (i.e., by 34 mg/dL and 9 mg/dL respectively, p<0.0001), compared to the normal group, while low-density lipoprotein cholesterol was lower (by 20 mg/dL and 6 mg/dL, respectively (p<0.0001). Similarly, in cases of subclinical hypothyroidism, the total cholesterol was higher by 5 mg/dL and 4 mg/dL, respectively, (p<0.05, p=0.015), as was the low-density lipoprotein cholesterol, by 2 mg/dL and 3 mg/dL (p<0.05, p=0.047). As a result of analyzing the TSH and lipid levels in 279 subjects of ≥65 in America, the total cholesterol was reported to have increased by 8% at high TSH versus the normal group, and the low-density lipoprotein cholesterol to have increased by 13%. Thus, though increases in the total cholesterol and low-density lipoprotein cholesterol shown in the present study are statistically significant, their degrees are small. In the present study, total cholesterol and low-density lipoprotein cholesterol did not increased in the men with only overt hypothyroidism. However, in women, the difference in the lipid levels of the subclinical and overt hypothyroidism groups was large. Therefore, screening tests for lipids are considered necessary for women. As a result of comparing hsCRP³⁴⁾, which has been reported as a strong independent prognostic factor for the risk of arteriosclerosis and cardiovascular diseases, with thyroid dysfunction itself, no significant difference was found. This is considered to be due to the relatively smaller number of the subject patients involved and a study is now being planned to complement address this. Thyroid hormones are known to play an important role in controlling the energy metabolism and obesity genes³⁵⁾. Therefore, body mass may change in cases of thyroid dysfunction. According to the study by Mehta et al.³⁶⁾, 14% of obese people with a body mass index of 30–40 kg/m² showed hypothyroidism, 8% of these were reported to be overt, and 6% had subclinical hypothyroidism. In this study, body mass index (BMI) and waist-hip ratio were measured as indicators of obesity, which is an important risk factor for cardiovascular diseases. However, thyroid function and BMI did not show any significant correlation, but the waist-hip ratio was found to be significantly higher in the hypothyroidism than in the normal group. Thus central obesity, which is a risk factor for cardiovascular diseases, was found to be significantly higher, especially in the hypothyroidism group. In conclusion, the prevalence of thyroid dysfunction in Korean people who are seemingly healthy was found to be lower than in the West, while the findings that its prevalence was higher in the aged and much higher in women concurred with finding published in West. In subclinical hypothyroidism especially, total cholesterol and low-density lipoprotein cholesterol, which are risk factors for cardiovascular diseases, were significantly elevated even after adjusting the age and gender ratio.

Therefore, we recommend that screening tests and treatment for subclinical hypothyroidism should be undertaken, and that further prospective studies should be initiated on determining the actual incidence of cardiovascular diseases in the subclinical hypothyroidal group.