Endocrinology and Metabolism

Review Article

Obesity and Metabolism
Effects of Cardiovascular Risk Factor Variability on Health Outcomes: Seung-Hwan Lee, Mee Kyoung Kim, Eun-Jung Rhee; Endocrinol Metab. 2020;35(2):217-226. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.217

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Innumerable studies have suggested “the lower, the better” for cardiovascular risk factors, such as body weight, lipid profile, blood pressure, and blood glucose, in terms of health outcomes. However, excessively low levels of these parameters cause health problems, as seen in cachexia, hypoglycemia, and hypotension. Body weight fluctuation is related to mortality, diabetes, obesity, cardiovascular disease, and cancer, although contradictory findings have been reported. High lipid variability is associated with increased mortality and elevated risks of cardiovascular disease, diabetes, end-stage renal disease, and dementia. High blood pressure variability is associated with increased mortality, myocardial infarction, hospitalization, and dementia, which may be caused by hypotension. Furthermore, high glucose variability, which can be measured by continuous glucose monitoring systems or self-monitoring of blood glucose levels, is associated with increased mortality, microvascular and macrovascular complications of diabetes, and hypoglycemic events, leading to hospitalization. Variability in metabolic parameters could be affected by medications, such as statins, antihypertensives, and hypoglycemic agents, and changes in lifestyle patterns. However, other mechanisms modify the relationships between biological variability and various health outcomes. In this study, we review recent evidence regarding the role of variability in metabolic parameters and discuss the clinical implications of these findings.

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Original Articles

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

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Abstract 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.

The Effects of Altered Membrane Cholesterol Levels on Sodium Pump Activity in Subclinical Hypothyroidism: Suparna Roy, Anindya Dasgupta; Endocrinol Metab. 2017;32(1):129-139. Published online February 28, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.129

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Abstract PDF PubReader: Background
Metabolic dysfunctions characteristic of overt hypothyroidism (OH) start at the early stage of subclinical hypothyroidism (SCH). Na⁺/K⁺-ATPase (the sodium pump) is a transmembrane enzyme that plays a vital role in cellular activities in combination with membrane lipids. We evaluated the effects of early changes in thyroid hormone and membrane cholesterol on sodium pump activity in SCH and OH patients.
Methods
In 32 SCH patients, 35 OH patients, and 34 euthyroid patients, sodium pump activity and cholesterol levels in red blood cell membranes were measured. Serum thyroxine (T₄) and thyroid stimulating hormone (TSH) levels were measured using enzyme-linked immunosorbent assays. Differences in their mean values were analysed using post hoc analysis of variance. We assessed the dependence of the sodium pump on other metabolites by multiple regression analysis.
Results
Sodium pump activity and membrane cholesterol were lower in both hypothyroid groups than in control group, OH group exhibiting lower values than SCH group. In SCH group, sodium pump activity showed a significant direct dependence on membrane cholesterol with an inverse relationship with serum TSH levels. In OH group, sodium pump activity depended directly on membrane cholesterol and serum T₄ levels. No dependence on serum cholesterol was observed in either case.
Conclusion
Despite the presence of elevated serum cholesterol in hypothyroidism, membrane cholesterol contributed significantly to maintain sodium pump activity in the cells. A critical reduction in membrane cholesterol levels heralds compromised enzyme activity, even in the early stage of hypothyroidism, and this can be predicted by elevated TSH levels alone, without any evident clinical manifestations.

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

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Abstract PDF PubReader

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.

Citations

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Determinants of Levothyroxine Treatment in Patients with Hypothyroidism
Savaş Karataş, Yalçın Hacıoğlu
Cyprus Journal of Medical Sciences.2022; 7(5): 593. CrossRef
Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape
Won Sang Yoo, Hyun Kyung Chung
Endocrinology and Metabolism.2021; 36(3): 500. CrossRef
Thyroid disorders in Brazil: the contribution of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
I.M. Bensenor
Brazilian Journal of Medical and Biological Research.2019;[Epub] CrossRef
Risk factors for hypothyroidism in euthyroid thyroid nodule patients with lymphocytic thyroiditis on fine needle aspiration cytology
Jeong-Min Lee, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Min-Hee Kim, Chan-Kwan Jung, So-Lyung Jung, Moo-Il Kang, Bong-Yun Cha, Dong-Jun Lim
The Korean Journal of Internal Medicine.2019; 34(6): 1287. CrossRef
Analysis of the factors affecting the evolution over time of subclinical hypothyroidism in children
Mariella Valenzise, Tommaso Aversa, Giuseppina Zirilli, Giuseppina Salzano, Domenico Corica, Simona Santucci, Filippo De Luca
Italian Journal of Pediatrics.2017;[Epub] CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
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Reference interval for thyrotropin in a ultrasonography screened Korean population
Mijin Kim, Tae Yong Kim, Soo Han Kim, Yunkyoung Lee, Su-yeon Park, Hyung-don Kim, Hyemi Kwon, Yun Mi Choi, Eun Kyung Jang, Min Ji Jeon, Won Gu Kim, Young Kee Shong, Won Bae Kim
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Subclinical hypothyroidism: a historical view and shifting prevalence
J. V. Hennessey, R. Espaillat
International Journal of Clinical Practice.2015; 69(7): 771. CrossRef
Letter: The Biochemical Prognostic Factors of Subclinical Hypothyroidism (Endocrinol Metab2014;29:154-62, Myung Won Lee et al.)
Hwa Young Ahn, Yun Jae Chung
Endocrinology and Metabolism.2014; 29(3): 400. CrossRef
The Biochemical Prognostic Factors of Subclinical Hypothyroidism
You Jin Lee
Endocrinology and Metabolism.2014; 29(2): 144. CrossRef

Lipid Profiles and Prevalence of Dyslipidemia in Korean Adolescents.: Shin Hye Kim, Byung Chul Ahn, Hyojee Joung, Mi Jung Park; Endocrinol Metab. 2012;27(3):208-216. Published online September 19, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.3.208

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Abstract PDF

BACKGROUND
The aim of this study is to investigate the distribution of plasma cholesterol and triglyceride levels as well as the prevalence of dyslipidemia among Korean adolescents. METHODS: We analyzed data for 3,045 adolescents aged 10-18 years (1,622 boys and 1,423 girls) who participated in the Korea National Health and Nutrition Examination Surveys from 2007 to 2010. RESULTS: The mean values of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were 159, 89, 89, and 52 mg/dL, respectively. Plasma cholesterol levels were significantly higher in girls than those in boys (162.1 mg/dL vs. 155.6 mg/dL, P < 0.0001). The 90th percentile values of total cholesterol, triglycerides, and LDL-C were 192, 149, 117 mg/dL for boys, and 195, 147, 119 mg/dL for girls. The 10th percentile value of HDL-C was 38 mg/dL for boys and 40 mg/dL for girls. Triglyceride, LDL-C cholesterol levels increased, whereas plasma HDL-C levels decreased with increasing the body mass index (P < 0.0001) in both genders. Total cholesterol levels significantly increased with increasing the body mass index, especially in boys (P < 0.0001). The prevalence of dyslipidemia was 25.2% for boys and 21.7% for girls; this value significantly increased with overweight (37-40%) and obesity (53-56%). Independent predictors (odds ratio) of dyslipidemia were age (1.49), overweight (2.06), and obesity (5.11) for boys; overweight (1.95) and obesity (3.22) for girls. CONCLUSION: Adolescent dyslipidemia is strongly associated with obesity. Lipid screening for overweight or obese youths should be emphasized. Further, longitudinal studies examining the impact of childhood obesity and dyslipidemia on subsequent cardiovascular diseases are needed.

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Jung Sub Lim, Eun Young Kim, Jae Hyun Kim, Jae-Ho Yoo, Kyung Hee Yi, Hyun Wook Chae, Jin-Ho Choi, Ji Young Kim, Il Tae Hwang
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Review Article

Mechanism of Lipid Induced Insulin Resistance: An Overview.: Samir Bhattacharya, Rakesh Kundu, Suman Dasgupta, Sushmita Bhattacharya; Endocrinol Metab. 2012;27(1):12-19. Published online March 1, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.1.12

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Abstract PDF

Type 2 diabetes (T2D) is rapidly spreading throughout the world. It's an insidious disease and still treated in an indirect manner without having specific drug target. In majority cases T2D is treated with drugs that address type 1 diabetes, majority of drugs aim to increase insulin release although the root cause for T2D is not the dearth of insulin release, it occurs in the later stage of disease development. T2D silently progressed in the patient; it begins with insulin resistance that takes place due to the loss of insulin sensitivity. Though insulin resistance is the centre of pathogenesis, our treatment of the disease has not yet addressed it. It is now a fact that insulin resistance is manifested by lipid and fatty acids (FAs) play a critical role in blunting insulin sensitivity. Our understanding is still poor in deciphering how lipid impose insulin insensitivity, majority of workers suggest it is because of insulin signaling defects which implements insulin function in inhibiting glucose to the cell from circulation. Number of long chain saturated FA has been shown to produce insulin signaling defects. However, we really need further investigation to find specific target(s) for FA induced damage. In addition to these information, a new dimension of T2D is getting attractive is fetuin-A/alpha2-Heremans-Schmid Glycoprotein, a secretary protein from liver. Its gene locus has been identified as T2D susceptible. Fetuin-A's excess expression occurs by FA and it disrupts adipocyte function. It has been shown to be associated with T2D especially in obesity. In this review, we briefly discuss the present status on the mechanistic understanding of lipid induced insulin resistance that leads to T2D. More we understand the mechanism; opportunity to fight the battle with T2D will be increasing. Since, this field is now vast; we covered a few major events.

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