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Thyroid
Management of Subclinical Hypothyroidism: A Focus on Proven Health Effects in the 2023 Korean Thyroid Association Guidelines
Eu Jeong Ku, Won Sang Yoo, Hyun Kyung Chung
Endocrinol Metab. 2023;38(4):381-391.   Published online August 8, 2023
DOI: https://doi.org/10.3803/EnM.2023.1778
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  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) and normal free thyroxine levels. The Korean Thyroid Association recently issued a guideline for managing SCH, which emphasizes Korean-specific TSH diagnostic criteria and highlights the health benefits of levothyroxine (LT4) treatment. A serum TSH level of 6.8 mIU/L is presented as the reference value for diagnosing SCH. SCH can be classified as mild (TSH 6.8 to 10.0 mIU/L) or severe (TSH >10.0 mIU/L), and patients can be categorized as adults (age <70 years) or elderly (age ≥70 years), depending on the health effects of LT4 treatment. An initial increase in serum TSH levels should be reassessed with a subsequent measurement, including a thyroid peroxidase antibody test, preferably 2 to 3 months after the initial assessment. While LT4 treatment is not generally recommended for mild SCH in adults, it is necessary for severe SCH in patients with underlying coronary artery disease or heart failure and it may be considered for those with concurrent dyslipidemia. Conversely, LT4 treatment is generally not recommended for elderly patients, regardless of SCH severity. For those SCH patients who are prescribed LT4 treatment, the dosage should be personalized, and serum TSH levels should be regularly monitored to maintain the optimal LT4 regimen.

Citations

Citations to this article as recorded by  
  • Clinical Implications of Different Thyroid-Stimulating Hormone (TSH) Reference Intervals between TSH Kits for the Management of Subclinical Hypothyroidism
    Won Sang Yoo
    Endocrinology and Metabolism.2024; 39(1): 188.     CrossRef
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Thyroid
Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape
Won Sang Yoo, Hyun Kyung Chung
Endocrinol Metab. 2021;36(3):500-513.   Published online June 18, 2021
DOI: https://doi.org/10.3803/EnM.2021.1066
  • 9,210 View
  • 552 Download
  • 16 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   ePub   
Subclinical hypothyroidism (sHypo) is defined as normal serum free thyroid hormone levels coexisting with elevated serum thyroid-stimulating hormone (TSH) levels. sHypo is a common condition observed in clinical practice with several unique features. Its diagnosis should be based on an understanding of geographic and demographic differences in biochemical criteria versus a global reference range for TSH that is based on the 95% confidence interval of a healthy population. During the differential diagnosis, it is important to remember that a considerable proportion of sHypo cases are transient and reversible in nature; the focus is better placed on persistent or progressive forms, which mainly result from chronic autoimmune thyroiditis. Despite significant evidence documenting the health impacts of sHypo, the effects of levothyroxine treatment (LT4-Tx) in patients with sHypo remains controversial, especially in patients with grade 1 sHypo and older adults. Existing evidence suggests that it is reasonable to refrain from immediate LT4-Tx in most patients if they are closely monitored, except in women who are pregnant or in progressive cases. Future research is needed to further characterize the risks and benefits of LT4-Tx in different patient cohorts.

Citations

Citations to this article as recorded by  
  • THYROID FUNCTION ABNORMALITIES IN PATIENTS WITH CHOLELITHIASIS: A HOSPITAL-BASED CROSS-SECTIONAL STUDY
    AVANISH KUMAR SAXENA, ANAM FATIMA, KUNDRAPU VEERA VENKATA SIVA, ANUSHKA PARIYA, VAYALAPALLI SYAMA CHINMAYI
    Asian Journal of Pharmaceutical and Clinical Research.2024; : 138.     CrossRef
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    Current Medical Research and Opinion.2023; 39(3): 351.     CrossRef
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    G. T. Makhkamova, Sh. T. Turdieva
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    Debbie Noelia Tebanta Albán, Gabriel Aníbal Hugo Merino, María Valentina Muñoz Arteaga, Ariana Lisseth Vázquez López
    Ciencia Digital.2023; 7(1): 6.     CrossRef
  • 2023 Korean Thyroid Association Management Guidelines for Patients with Subclinical Hypothyroidism
    Hyun Kyung Chung, Eu Jeong Ku, Won Sang Yoo, Yea Eun Kang, Kyeong Jin Kim, Bo Hyun Kim, Tae-Yong Kim, Young Joo Park, Chang Ho Ahn, Jee Hee Yoon, Eun Kyung Lee, Jong Min Lee, Eui Dal Jung, Jae Hoon Chung, Yun Jae Chung, Won Bae Kim, Ka Hee Yi, Ho-Cheol Ka
    International Journal of Thyroidology.2023; 16(1): 32.     CrossRef
  • Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases
    María José Mendoza-León, Ashutosh K. Mangalam, Alejandro Regaldiz, Enrique González-Madrid, Ma. Andreina Rangel-Ramírez, Oscar Álvarez-Mardonez, Omar P. Vallejos, Constanza Méndez, Susan M. Bueno, Felipe Melo-González, Yorley Duarte, Ma. Cecilia Opazo, Al
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Human amnion-derived mesenchymal stem cells improve subclinical hypothyroidism by immunocompetence mediating apoptosis inhibition on thyroid cells in aged mice
    Chuyu Li, Qiang Rui, Xiaohan Dong, Song Ning, Jing Zhou, Huimin Wu, Chunyan Jiang, Yugui Cui, Jiayin Liu, Jun Jiang, Lianju Qin
    Cell and Tissue Research.2023; 394(2): 309.     CrossRef
  • Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case–Control Study from Korea
    Hyeree Park, Sun Wook Cho, Sung Ho Lee, Kangmin Kim, Hyun-Seung Kang, Jeong Eun Kim, Aesun Shin, Won-Sang Cho
    Thyroid®.2023; 33(12): 1483.     CrossRef
  • The Role of Global Longitudinal Strain in Subclinical Hypothyroid Patients With Heart Failure
    Nismat Javed, Vibha Hayagreev, Angel DeLaCruz, Muhammad Saad, Amandeep Singh, Timothy Vittorio
    Cureus.2023;[Epub]     CrossRef
  • Association between shift work and the risk of hypothyroidism in adult male workers in Korea: a cohort study
    Seonghyeon Kwon, Yesung Lee, Eunhye Seo, Daehoon Kim, Jaehong Lee, Youshik Jeong, Jihoon Kim, Jinsook Jeong, Woncheol Lee
    Annals of Occupational and Environmental Medicine.2023;[Epub]     CrossRef
  • Estimation of left ventricular functions in patients with subclinical hypothyroidism: a meta-analysis
    Binyi Li, Yong Huang, Zheng Li
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • Comparison of Five Different Criteria for Diagnosis of Subclinical Hypothyroidism in a Large-Scale Chinese Population
    Yan-song Zheng, Sheng-yong Dong, Yan Gong, Jia-hong Wang, Fei Wang, Qiang Zeng
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Subclinical Hypothyroidism and Cognitive Impairment
    Jung-Min Pyun, Young Ho Park, SangYun Kim
    Journal of Alzheimer's Disease.2022; 88(2): 757.     CrossRef
  • Effect of Levothyroxine Supplementation on the Cardiac Morphology and Function in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis
    Xichang Wang, Haoyu Wang, Qiuxian Li, Ping Wang, Yumin Xing, Fan Zhang, Jiashu Li, Zhongyan Shan
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(9): 2674.     CrossRef
  • Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS)
    A. Amouzegar, M. Dehghani, H. Abdi, L. Mehran, S. Masoumi, F. Azizi
    Journal of Endocrinological Investigation.2022; 45(12): 2353.     CrossRef
  • Retrospective cohort analysis comparing changes in blood glucose level and body composition according to changes in thyroid‐stimulating hormone level
    Hyunah Kim, Da Young Jung, Seung‐Hwan Lee, Jae‐Hyoung Cho, Hyeon Woo Yim, Hun‐Sung Kim
    Journal of Diabetes.2022; 14(9): 620.     CrossRef
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    Yesung Lee, Woncheol Lee, Hyoung-Ryoul Kim
    Epidemiology and Health.2022; 44: e2022104.     CrossRef
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Original Article
Changes in Serum Lipids and Apolipoproteins Levels According to the Thyroxine Treatment in The Patients with Subclinical Hypothyroidism.
Hye Young Park, Bo Youn Cho, Won Bae Kim, Hong Gyu Lee, Chang Soon Koh, Geon Sang Park, Hyung Kyu Park, Sook Kyung Kim, Chan Soo Shin, Seong Yeon Kim
J Korean Endocr Soc. 1996;11(1):41-51.   Published online November 7, 2019
  • 1,221 View
  • 21 Download
AbstractAbstract PDF
Background
Subclinical hypothyroidism(SCH) is a common biochemical abnormality which can be found in routine screening tests of thyroid function. We are increasingly faced with the question of whether its an indication for thyroxine replacement therapy. The effect of thyroxine replacement on lipid profile in SCH has aroused a great interest because of an association of overt hypothyroidism(OVH) with hyperlipidemia and increased risk of coronary artery disease. Method: We prospectively evaluated the changes in lipids and apoproteins before and after thyroxine replacement therapy in 23 patients with SCH and in 37 patients with OVH. We measured serum total cholesterol and triglyceride using autoanalyzer, high density lipoprotein(HDL) chole-sterol by dextran sulfate method, Apo A1 and Apo B by immunonephelometric assay. Results: Thyroxine replacement therapy significantly decreased total cholesterol, low density lipoprotein(LDL) cholesterol and apo B levels, but did not affect the level of triglyceride, HDL cholesterol or apo AI in patients with OVH. In SCH, thyroxine replacement therapy with the doses to normalize serum TSH concentrations also decreased significantly the level of cholesterol and LDL cholesterol albeit apo B levels did not change. Moreover, in most of patients with OVH (11 of 12) and in all of patients with SCH(5 of 5) who had had hyperchlesterolemia before treatment, thyroxine replament normalized their cholesterol and LDL cholesterol levels. Conclusion: In regard to the beneficial changes in blood lipid levels, patients with SCH should be treated, especially in cases who have other risk factors for the development of atherosclerosis. If thyroxine replacement only will reduce the incidence of coronary artery disease in SCH remains to be elucidated by long-term prospective studies.
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Case Report
A Case of Subclinical Hypothyroidism Associated with Turner's Syndrome.
In Kwon Han, Jung Gil Lee, Sun Wha Lee, Seong Kyu Lee, Chan Moon Pak, Ho Yeon Chung
J Korean Endocr Soc. 1994;9(1):35-38.   Published online November 6, 2019
  • 1,252 View
  • 20 Download
AbstractAbstract PDF
Recently it is known that Turner's syndrome is frequently associated with hypothyroidism. We report a case of Turner's syndrome associated with subclinical hypothyroidism. A 23-year-old female was admitted to the hospital with complaints of amenorrhea and short stature. She had a mosaicism of 45, X0/46, Xi(X_q) in the cell, cultured from the peripheral blood. The plasma thyroxine and triiodothyronine were normal and there was no clinical symptom of hypothyroidism. But the thyroid-stimulating hormone(TSH) concentration was unusually higher(184 uU/L). She has been treated with the cyclic therapy of conjugated estrogen and medroxyprogesterone, in addition to the thyroxine replacement therapy. After 2 months, the menstruation was restored and TSH was normalized.
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Review Article
Thyroid
Subclinical Hypothyroidism and Cardiovascular Disease
Sunghwan Suh, Duk Kyu Kim
Endocrinol Metab. 2015;30(3):246-251.   Published online August 4, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.246
  • 4,935 View
  • 68 Download
  • 31 Web of Science
  • 29 Crossref
AbstractAbstract PDFPubReader   

Subclinical hypothyroidism (SCH) is a common disorder that is characterized by elevated thyroid-stimulating hormone levels in conjunction with free thyroxine concentrations within the normal reference range. Thyroid hormones are known to affect the heart and vasculature and, as a result, the impact of SCH on the cardiovascular (CV) system has recently become an important topic of research. Strong evidence points to a link between SCH and CV risk factors such as alterations in blood pressure, lipid levels, and atherosclerosis. Additionally, accumulating evidence indicates that SCH is associated with metabolic syndrome and heart failure. The present review proposes that SCH may be a potentially modifiable risk factor of CV disease and mortality. However, large-scale clinical trials with appropriate power investigating the risks and benefits of SCH treatment are required to determine whether these benefits can be achieved with levothyroxine therapy.

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    Selvihan BEYSEL, Mahmut APAYDIN, Mustafa ÇALIŞKAN, Mustafa ÖZBEK, Erman ÇAKAL
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Original Article
Thyroid
The Biochemical Prognostic Factors of Subclinical Hypothyroidism
Myung Won Lee, Dong Yeob Shin, Kwang Joon Kim, Sena Hwang, Eun Jig Lee
Endocrinol Metab. 2014;29(2):154-162.   Published online June 26, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.2.154
  • 3,623 View
  • 50 Download
  • 14 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   
Background

Patients with subclinical hypothyroidism (SHT) are common in clinical practice. However, the clinical significance of SHT, including prognosis, has not been established. Further clarifying SHT will be critical in devising a management plan and treatment guidelines for SHT patients. Thus, the aim of this study was to investigate the prognostic factors of SHT.

Methods

We reviewed the medical records of Korean patients who visited the endocrinology outpatient clinic of Severance Hospital from January 2008 to September 2012. Newly-diagnosed patients with SHT were selected and reviewed retrospectively. We compared two groups: the SHT maintenance group and the spontaneous improvement group.

Results

The SHT maintenance group and the spontaneous improvement group had initial thyroid-stimulating hormone (TSH) levels that were significantly different (P=0.035). In subanalysis for subjects with TSH levels between 5 to 10 µIU/mL, the spontaneous improvement group showed significantly lower antithyroid peroxidase antibody (anti-TPO-Ab) titer than the SHT maintenance group (P=0.039). Regarding lipid profiles, only triglyceride level, unlike total cholesterol and low density lipoprotein cholesterol, was related to TSH level, which is correlated with the severity of SHT. Diffuse thyroiditis on ultrasonography only contributed to the severity of SHT, not to the prognosis. High sensitivity C-reactive protein and urine iodine excretion, generally regarded as possible prognostic factors, did not show any significant relation with the prognosis and severity of SHT.

Conclusion

Only initial TSH level was a definite prognostic factor of SHT. TPO-Ab titer was also a helpful prognostic factor for SHT in cases with mildly elevated TSH. Other than TSH and TPO-Ab, we were unable to validate biochemical prognostic factors in this retrospective study for Korean SHT patients.

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Close layer
Review Article
Thyroid
Prevalence and Risk Factors of Subclinical Thyroid Disease
Ye An Kim, Young Joo Park
Endocrinol Metab. 2014;29(1):20-29.   Published online March 14, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.1.20
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AbstractAbstract PDFPubReader   

Subclinical thyroid disease is defined biochemically by an abnormal thyrotropin (TSH) level and normal serum-free thyroxine level. The prevalence of this condition varies according to the reference range for TSH and geographic or demographic factors. Recently, several studies, including our community-based cohort studies, have reported on the incidence of subclinical thyroid disease in Korea. Using these studies, we reviewed the prevalence and risk factors of subclinical thyroid disease, focusing on subclinical hypothyroidism.

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Original Articles
Thyroid Dysfunction of North Korean Women Living in South Korea, Focusing on Subclinical Hypothyroidism.
Joo Hyung Kim, Sol Ah Park, Nam Hoon Kim, Jae Hee Ahn, Yoon Jung Kim, Myongjin Cho, Yoon Jung Lee, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim
Endocrinol Metab. 2012;27(3):200-207.   Published online September 19, 2012
DOI: https://doi.org/10.3803/EnM.2012.27.3.200
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AbstractAbstract PDF
BACKGROUND
Thyroid function depends on ethnic and environmental factors. North Korean refugees have the same genetic background as South Koreans, but they have been exposed to different environments. This study examines the prevalence and pattern of thyroid disorders in North Korean women living in South Korea, focusing on subclinical hypothyroidism (SCH). METHODS: The intended sample was a total of 327 North Korean women residing in Seoul. Health questionnaires and medical examinations, including serum thyrotropin (thyroid stimulating hormone, TSH), free thyroxine, and thyroid autoantibodies, were conducted. RESULTS: The prevalence of SCH was 9.4%. In logistic regression analysis, smoking, menopause, length of stay in South Korea, body mass index, history of thyroid disease, and metabolic syndrome were not associated with the risk of SCH. Whereas, the positivity of autoantibodies were associated with a high risk for SCH (odds ratio [OR], 4.840; 95% confidence interval [CI], 1.80-13.017; P = 0.002), and age was associated with a low risk for SCH (OR, 0.94; 95% CI, 0.888-0.994; P = 0.031). The serum TSH levels also decreased with increasing age, and in particular, there was significant difference between 30-39 years, and over 60 years (2.33 +/- 1.51 microIU/mL vs. 1.54 +/- 0.73 microIU/mL, P = 0.028). CONCLUSION: In North Korean women, the positivity of autoantibodies was associated with a high risk for SCH. But interestingly, a younger age was associated with a high risk for SCH. Considering that they suffered from severe famine at the period of growth, and this led to malnutrition, their thyroid dysfunction might be associated with the peculiar environment that they experienced.

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  • Systematic review of evidence on public health in the Democratic People’s Republic of Korea
    John J Park, Ah-Young Lim, Hyung-Soon Ahn, Andrew I Kim, Soyoung Choi, David HW Oh, Owen Lee-Park, Sharon Y Kim, Sun Jae Jung, Jesse B Bump, Rifat Atun, Hee Young Shin, Kee B Park
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  • Environmental Factors and Thyroid Dysfunction
    Hyun-Kyung Chung
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Comparison of Common Carotid Artery Intima-Media Thickness between Subclinical Hypothyroidism and Euthyroidism.
Kyung Sun Park, Jung Im Rue, Soo Kyung Kim, In Jae Kim, Sang Wook Lim, Seok Won Park, Yu Lee Kim, Dong Hoon Cha, Yong Wook Cho, Young Kil Choi, Sang Jong Lee
J Korean Endocr Soc. 2006;21(6):490-496.   Published online December 1, 2006
DOI: https://doi.org/10.3803/jkes.2006.21.6.490
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  • 2 Crossref
AbstractAbstract PDF
BACKGROUND
Common carotid artery intima-media thickness (IMT), which is increased in patients with overt hypothyroidism, is an independent risk factor of the atherosclerosis-related disease. This study was performed to compare serum lipid level and common carotid artery IMT among patients with overt hypothyroidism, subclinical hypothyroidism and euthyroidism. METHODS: Patients with newly-diagnosed subclinical (n=32) and overt (n=32) hypothyroidism were selected for this study. All of the patients and an age- and sex-matched euthyroidism cohort were checked for clinical characteristics and serum lipid levels. Common carotid artery IMT was also measured using high resolution B-mode ultrasonography. RESULTS: Statistically significant differences were observed between the total cholesterol levels of patients with subclinical hypothyroidism and those with euthyroidism. When common carotid artery IMT measured by ultrasonography, subclinical (0.67 +/- 0.11 mm) and overt (0.71 +/- 0.12 mm)) hypothyroidism showed significantly increased mean IMT compared to that of euthyroidism (0.58 +/- 0.07 mm, P < 0.05, respectively), but no differences were found between subclinical and overt hypothyroidism. CONCLUSION: We concluded that subclinical hypothyroidism is related to increased common carotid artery IMT as well as dyslipidemia. Therefore, we recommend that treatment principle of subclinical hypothyroidism be established through large-scale, prospective studies performed to determine the effect of thyroid hormone replacement on the reduction of common carotid artery IMT.

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Serum Lipoprotein (a) and Lipid Concentrations in Patients with Subelinical Hypothyroidism.
Kyoung Ah Kim, Jae Hoon Chung, Yeun Sun Kim, Kyu Jeung Ahn, Eun Mi Koh, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Jong Hun Lee, Kwang Won Kim
J Korean Endocr Soc. 1997;12(1):11-17.   Published online January 1, 2001
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  • 17 Download
AbstractAbstract PDF
BACKGROUND
Overt hypothyroidism is well-known cause of secondary hyperlipidemia and atherosclerosis. However, there have been dissenting reports of abnormalities in serum lipid concentrations in patients with subclinical hypothyroidism (SH). Recently, it has been reported that serum Lp (a) concentration, an independent risk factor of atherosclerosis, was increased in patients with SH. Therefore, we analyzed serum Lp (a) and other lipid concentrations to investigate whether they are increased in patients with SH and the correlation between serum Lp (a) and TSH concentrations. METHODS: We undertook this study in 53 patients with SH (TSH > 6 uiU/ml) and 197 age-and sex-matched healthy control subjects, They had no abnormalities in liver function, BUN, creatinine, fasting blood glucose, urinalysis, and past medical histories. Serum T3, T4, and TSH concentrations were measured by RIA using commercial kits. Serum concentrations of Lp (a), total cholesterol, triglyceride (TG), and HDL cholesterol (HDL-C) were measured by rate nephelometry and enzyme assay, respectively. RESULTS: There were no significant differences of serum Lp (a), total cholesterol, LDL cholesterol, TG, and HDL-C concentrations in 53 patients with SH and 197 control subjects (25.6+-3.8mg/dL vs. 25.4+-1.5mg/dL ; 204.0+-4.2mg/dL vs. 204.0+-2.4mg/dL ; 127.0+-3.9mg/dL vs. 125.0+-2.3 mg/dL ; 133.0+-8.5mg/dL vs. 130.0+-6.0mg/dL ; 50.0+-1.5mg/dL vs. 53.0+-0.9mg/dL). There was no correlation between Lp (a) and TSH concentrations in SH (r=0.12, p>0.05). CONCLUSION: Serum Lp (a) concentration as well as total cholesterol, LDL cholesterol, and TG was not increased in patients with SH. There was no correlation between serum Lp (a) and TSH levels in subclinical hypothyroidism.
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Endocrinol Metab : Endocrinology and Metabolism