Endocrinology and Metabolism

Original Articles

Thyroid Big Data Articles (National Health Insurance Service Database)
Repeated Low High-Density Lipoprotein Cholesterol and the Risk of Thyroid Cancer: A Nationwide Population- Based Study in Korea: Jinyoung Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Kyungdo Han, Hyuk-Sang Kwon; Endocrinol Metab. 2022;37(2):303-311. Published online April 6, 2022; DOI: https://doi.org/10.3803/EnM.2021.1332

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Background
High-density lipoprotein cholesterol (HDL-C) plays an important role in the reverse cholesterol transport pathway and prevents atherosclerosis-mediated disease. It has also been suggested that HDL-C may be a protective factor against cancer. However, an inverse correlation between HDL-C and cancer has not been established, and few studies have explored thyroid cancer.
Methods
The study participants received health checkups provided by the Korean National Health Insurance Service from 2009 to 2013 and were followed until 2019. Considering the variability of serum HDL-C level, low HDL-C level was analyzed by grouping based on four consecutive health checkups. The data analysis was performed using univariate and multivariate Cox proportional hazard regression models.
Results
A total of 3,134,278 total study participants, thyroid cancer occurred in 16,129. In the crude model, the hazard ratios for the association between repeatedly measured low HDL-C levels and thyroid cancer were 1.243, 1.404, 1.486, and 1.680 (P for trend <0.01), respectively, which were significant even after adjusting for age, sex, lifestyle factors, and metabolic diseases. The subgroup analysis revealed that low HDL-C levels likely had a greater impact on the group of patients with central obesity (P for interaction= 0.062), high blood pressure (P for interaction=0.057), impaired fasting glucose (P for interaction=0.051), and hyperlipidemia (P for interaction=0.126).
Conclusion
Repeatedly measured low HDL-C levels can be considered a risk factor for cancer as well as vascular disease. Low HDL-C levels were associated with the risk of thyroid cancer, and this correlation was stronger in a metabolically unhealthy population.

Citations

Citations to this article as recorded by

Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer
Seohyun Kim, Gyuri Kim, So Hyun Cho, Rosa Oh, Ji Yoon Kim, You-Bin Lee, Sang-Man Jin, Kyu Yeon Hur, Jae Hyeon Kim
Scientific Reports.2024;[Epub] CrossRef
Association between organophosphate flame retardant exposure and lipid metabolism: data from the 2013–2014 National Health and Nutrition Examination Survey
Fu-Jen Cheng, Kai-Fan Tsai, Kuo-Chen Huang, Chia-Te Kung, Wan-Ting Huang, Huey-Ling You, Shau-Hsuan Li, Chin-Chou Wang, Wen-Chin Lee, Hsiu-Yung Pan
Frontiers in Public Health.2024;[Epub] CrossRef
Low serum total cholesterol levels predict inferior prognosis of patients with POEMS syndrome
Jue Zhang, Ting Zhang, Ye Yao, Xuxing Shen, Yuanyuan Jin, Run Zhang, Lijuan Chen
Discover Oncology.2024;[Epub] CrossRef
Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field
Michal Olejarz, Ewelina Szczepanek-Parulska, Marek Ruchala
Frontiers in Endocrinology.2024;[Epub] CrossRef
Carbohydrate, Lipid, and Apolipoprotein Biomarkers in Blood and Risk of Thyroid Cancer: Findings from the AMORIS Cohort
Xue Xiao, Yi Huang, Fetemeh Sadeghi, Maria Feychting, Niklas Hammar, Fang Fang, Zhe Zhang, Qianwei Liu
Cancers.2023; 15(2): 520. CrossRef
Altered serum lipid levels are associated with prognosis of diffuse large B cell lymphoma and influenced by utility of rituximab
Fei Wang, Luo Lu, HuiJuan Chen, Yanhua Yue, Yanting Sun, Feng Yan, Bai He, Rongrong Lin, Weiying Gu
Annals of Hematology.2023; 102(2): 393. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
High-density lipoprotein cholesterol and carcinogenesis
Meijuan Tan, Shijie Yang, Xiequn Xu
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Low Serum Cholesterol Level Is a Significant Prognostic Factor That Improves CLL-IPI in Chronic Lymphocytic Leukaemia
Rui Gao, Kaixin Du, Jinhua Liang, Yi Xia, Jiazhu Wu, Yue Li, Bihui Pan, Li Wang, Jianyong Li, Wei Xu
International Journal of Molecular Sciences.2023; 24(8): 7396. CrossRef
Do metabolic factors increase the risk of thyroid cancer? a Mendelian randomization study
Weiwei Liang, FangFang Sun
Frontiers in Endocrinology.2023;[Epub] CrossRef
Assessment of causal association between differentiated thyroid cancer and disordered serum lipid profile: a Mendelian randomization study
Qiang Ma, Yu Li, Lijuan An, Liang Guo, Xiaokang Liu
Frontiers in Endocrinology.2023;[Epub] CrossRef
Risk factors and diagnostic prediction models for papillary thyroid carcinoma
Xiaowen Zhang, Yuyang Ze, Jianfeng Sang, Xianbiao Shi, Yan Bi, Shanmei Shen, Xinlin Zhang, Dalong Zhu
Frontiers in Endocrinology.2022;[Epub] CrossRef
Exposure to multiple trace elements and thyroid cancer risk in Chinese adults: A case-control study
Jia-liu He, Hua-bing Wu, Wen-lei Hu, Jian-jun Liu, Qian Zhang, Wei Xiao, Ming-jun Hu, Ming Wu, Fen Huang
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Diabetes, Obesity and Metabolism
Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat: Sun Ok Song, You-Cheol Hwang, Han Uk Ryu, Steven E. Kahn, Donna L. Leonetti, Wilfred Y. Fujimoto, Edward J. Boyko; Endocrinol Metab. 2021;36(4):835-844. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1130

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Background
Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.
Methods
All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.
Results
A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm² in men and 63.1±39.5 cm² in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.
Conclusion
These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Citations

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Fenofibrate add-on to statin treatment is associated with low all-cause death and cardiovascular disease in the general population with high triglyceride levels
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
Metabolism.2022; 137: 155327. CrossRef
The associations between lipid profiles and visceral obesity among gastrointestinal cancer patients: a cross-sectional study
Bo Gao, Xiangrui Li, Wenqing Chen, Shu’an Wang, Jian He, Yu Liu, Chao Ding, Xiaotian Chen
Lipids in Health and Disease.2022;[Epub] CrossRef

Review Articles

Obesity and Metabolism
High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis: Alice Ossoli, Chiara Pavanello, Laura Calabresi; Endocrinol Metab. 2016;31(2):223-229. Published online June 10, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.223

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Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system.

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Obesity and Metabolism
High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes: Philip J. Barter; Endocrinol Metab. 2013;28(3):169-177. Published online September 13, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.3.169

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High density lipoproteins (HDLs) have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic β cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

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Original Articles

APOA5 Polymorphism Is Associated with Metabolic Syndrome in Korean Postmenopausal Women.: Doh Hee Kim, Seung Hee Lee, Kyung Hoon Han, Chae Bong Kim, Kwan Young Song, Sook Cho, Kye Heui Lee; Endocrinol Metab. 2012;27(4):276-281. Published online December 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.4.276

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BACKGROUND
Menopause is an independent risk factor in metabolic syndrome which induced an alteration of the lipid metabolism by hormonal changes. Apolipoprotein A5 gene (APOA5) was related to the regulation of triglyceride and high density lipoprotein cholesterol (HDL-C) level with biosynthesis and decomposition. This study was conducted to investigate the relationship between APOA5 polymorphism and metabolic syndrome in Korean postmenopausal women. METHODS: This study included 307 postmenopausal women with anthropometric and biochemical measurement in 2010-2011. The polymorphism of APOA5 was analyzed by polymerase chain reaction-restriction fragment length polymorphism method with MseI restriction enzyme. RESULTS: The metabolic syndrome prevalence with TT genotype was significantly lower than the frequency in those with TC/CC (27.09%, 38.46%, and 45.71% for TT, TC, and CC, respectively; P < 0.05). Multiple regression analysis of metabolic syndrome risk factors indicated that postmenopausal women with CC genotype had a higher risk with 3 times than that in TT genotype (P < 0.05). APOA5 C carriers showed an increased risk of triglyceride level (odd ratio, 2.93 and 1.85 for CC and TC+CC, respectively; P < 0.05). Interestingly, HDL-C was related to triglyceride directly in comparison to APOA5. CONCLUSION: The results of this study indicate that APOA5 has an influence on serum triglyceride and HDL-C, which contribute to metabolic syndrome in Korean postmenopausal women.

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Effects of a 3-year dietary intervention on age-related changes in triglyceride and apolipoprotein A-V levels in patients with impaired fasting glucose or new-onset type 2 diabetes as a function of the APOA5 -1131 T > C polymorphism
Minjoo Kim, Jey Sook Chae, Miri Kim, Sang-Hyun Lee, Jong Ho Lee
Nutrition Journal.2014;[Epub] CrossRef
APOA5Polymorphism Is Associated with Metabolic Syndrome in Korean Postmenopausal Women
Mi Hae Seo, Won Young Lee
Endocrinology and Metabolism.2012; 27(4): 274. CrossRef

Lipid Profile Changes in Postmenopausal Korean Women Treated with Alendronate (10 mg) for 2 Years: Comparing with Control Group.: Il Woo Joo, Han Jin Oh; J Korean Endocr Soc. 2007;22(1):19-25. Published online February 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.1.19

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BACKGROUND
Bisphosphonate, which has been used for prevention and treatment of osteoporosis with the mechanism of inhibiting bone resorption, also has an association with the cholesterol synthethic process. This suggests that bisphosphonate might have benefit to improve the lipid profile in humans through a process that blocks the mevalonate-squalene pathway. However, few reports have revealed the relationship between the action of bisphosphonate and lipid metabolism in postmenopausal Korean women. We planned this study to determine the effect of alendronate (10 mg) on the serum lipid level in postmenopausal Korean women. Subjects and METHODS: We retrospectively evaluated the postmenopausal Korean women (aged over 50) who visited the Osteoporosis clinic in the Health Care Center in Seoul from March of 2003 to October of 2005. The changes of the serum lipid levels, including total cholesterol, triglyceride, and HDL cholesterol, after 2-years of alendronate 10 mg administration were evaluated and comparing to a control group. RESULTS: After 2-years alendronate (10 mg) administration, the total cholesterol was decreased by 11.8 +/- 3.7 mg/dL, and the HDL cholesterol was increased by 5.2 +/-1.4 mg/dL as compared to the baseline lipid level. Both of these results showed statistical significance. Changes of the triglyceride and fasting blood glucose also showed a decline by 15.4 +/-9.8 mg/dL and 6.0 +/-1.4 mg/dL, respectively, but this was not statistically significant. However, in the control group, the total cholesterol was increased by 9.4 +/-8.8 mg/dL, and the triglyceride was increased by 10.5 +/-7.2 mg/dL as compared to the baseline lipid level. Both of the results showed statistical significance. CONCLUSION: Alendronate might have a beneficial effect on lipid metabolism to decrease cholesterol and increase HDL. Taking into consideration about the postmenopausal increase in the cholesterol level, alendronate is recommended for the prevention of hyperlipidemia in postmenopausal women, in addition to preventing and treating osteoporosi

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The effect of alendronate on lipid profile of postmenopausal women with osteopenia and prediabetes: A randomized triple-blind clinical trial
Maryam Karimifard, Ashraf Aminorroaya, Massoud Amini, Ali Kachuie, Awat Feizi, SimaAminorroaya Yamini, MolukHadi Alijanvand
Journal of Research in Medical Sciences.2021; 26(1): 52. CrossRef

Relationship between Adiponectin, Leptin and Body Fat in Men with Hypogonadism Before and After Testosterone Treatment.: Sang Wan Kim, Joon Ku Kang, Do Joon Park, Chan Soo Shin, Kyung Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee; J Korean Endocr Soc. 2004;19(5):473-484. Published online October 1, 2004

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Abstract PDF: BACKGROUND
Testosterone replacement therapy in men with hypogonadism improves sexual function, decreases body fat, and increases the mass and function of lean muscle. These beneficial effects of testosterone replacement therapy are accompanied by slight lowering of the high density lipoprotein (HDL) cholesterol levels, increase in the hematocrit/hemoglobin ratio and size of the prostate gland. It is presently unknown whether the effect of testosterone on body fat could also reduce the risk of atherosclerotic disease associated with obesity. We investigated the relationship between body fat and blood leptin and adiponectin levels to elucidate the effect of testosterone on body fat metabolism, as well as the effect of testosterone on lipid and bone metabolism. METHODS: We selected 28 men, who were hypogonadal (mean serum testosterone+/-SD, 22.3+/-35.3 ng/dL) due to an organic disease, and them with oral testosterone (testosterone undecanoate) for 12 months. We measured the body composition, serum leptin, plasma adiponectin, biochemical bone markers, bone mineral density, prostate-specific antigen, and serum lipids before and 3, 6 and 12 months after treatment. We analyzed the relationship between body fat and blood leptin and adiponectin levels. RESULTS: The mean serum testosterone concentration reached the subnormal range after 6 months of treatment, which remained for the duration of treatment. The fat mass decreased and muscle mass increased, not within the first 6 months, but principally within 12 months (p<0.05). Although the decrease in the serum leptin level was not statistically significant, there were positive correlations between the leptin level and fat mass before and after 6 months of treatment (p<0.05). The plasma adiponectin did not increase or correlate with body fat parameters. The bone mineral densities of the lumbar spine (L2-L4) and femoral neck did not increased, but the serum osteocalcin and urine N-telopeptide were significantly decreased (p<0.05 and <0.01, respectively). The HDL-cholesterol decreased, principally within the first 6 months (p<0.01), but the total and LDL cholesterols, and the triglycerides remained unchanged during the course of treatment. There was also no change in prostate-specific antigen. CONCLUSION: Twelve months of oral testosterone replacement in men with hypogonadism improved body composition and bone metabolism, but demonstrated subnormal serum testosterone levels, had no effect on the leptin and adiponectin levels and decrease in HDL-cholesterol levels. It will be necessary to examine the long-term effects of testosterone replacement on the incidence of cardiovascular events as well as cardiovascular risk factors in men with hypogonadism

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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Abstract 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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