Association Of Thyroid-stimulating Hormone Research Articles

Abstract P197: The Relationship Between Thyroid-Stimulating Hormone Levels and Lipoprotein Subfractions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Background and purpose: Although the relation between thyroid disorders and heart diseases had been described since decades ago, the association of thyroid-stimulating hormone (TSH) and lipoproteins is not very well elucidated. Hypothesis: to verify if there are associations with TSH levels, lipid and lipoprotein subfractions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: We evaluated at the ELSA-Brasil baseline (2008-2010) 3,742 middle-aged participants (1,960 women and 1,782 women) without previous cardiovascular disease and people who were taking neither drugs that can interfere with thyroid function nor lipid-lowering agents. All of them had their levels of total-cholesterol and its sub-fractions (LDL, VLDL and HDL subclasses); triglycerides and triglyceride-rich lipoprotein cholesterol [TRL-C (VLDL1+2-C VLDL3-C + IDL-C)] determined by ultracentrifugation (Vertical Auto Profile, Atherotech). We also calculated T-Chol/HDL-C and triglycerides/HDL-C ratios. The application multinomial logistic regression model obtained odds ratios (OR) with its respective 95% confidence interval (95% CI). They are presented as adjusted for age, sex, educational level, hypertension, diabetes, and smoking. Lipids tertiles were evaluated as dependent variables, the quintiles of TSH were considered as an independent variable, using first quintiles of TSH as the reference. Results: The main associations obtained were between the highest levels of TSH (5th quintile) with the highest levels (3rd tertiles) of VLDL-C, OR=1.55 (95%CI, 1.18-2.04); triglycerides, OR=1.71 (95%CI, 1.30-2.24); VLDL-3-C, OR=1.48 (95%CI, 1.13-1.94); TC/HDL-C ratio, OR=1.37 (95%CI; 1.04-1.81) and TG/HDL-C ratio, OR=1.71 (95%CI; 1.29-2.26). A positive association between the lowest levels of HDL3-C (1st tertile) and the highest of TSH was also verified with OR= 1.43 (95%CI, 1.10-1.87). In women, we found positive associations with the 5th TSH quintiles and the 3rd tertiles of VLDL-C, OR 1.68;(95%CI 1.18-2.41); non-HDL-C, OR,1.50; (95%CI,1.04-2.16); Triglyceride-rich Lipoprotein Cholesterol,OR 1.42 (95%CI 1.00-2.02); VLDL3-C (OR,1.68;95%CI 1.16-2.45), TC/HDL-C ratio (OR 1.86;95% CI 1.29-2.69) and TG/HDL-C-ratio (OR 1.62;95%CI 1.12-2.35). In men, we found associations between the 5th quintile of TSH and the 3rd tertiles of TG (OR 1.59; 95%CI 1.07-2.36) and TG/HDL-C-ratio (OR 1.71; 95%CI 1.15-2.55). Conclusions: In this sample of middle-aged participants from ELSA-Brasil, an unfavorable lipid profile, which included triglyceride-rich lipoproteins and their remnants were mostly associated with high levels of TSH. In the other hand, we observed a risky association between the lowest levels of HDL3-C and the highest levels of TSH. The majority of our findings were mainly reproduced among women.

Age- and gender-specific reference intervals of TSH and free T4 in an iodine-replete area: Data from Korean National Health and Nutrition Examination Survey IV (2013-2015).

BackgroundEstablishment of the reference interval of thyroid-stimulating hormone (TSH) is critical in the diagnosis of thyroid dysfunction and is affected by age, gender, iodine nutrition, and ethnicity. The aim of this study was to determine the reference intervals of TSH and free thyroxin (FT4) from a large, nationwide data of Korea where iodine intake is more than adequate.MethodsWe analyzed data from the Korea National Health and Nutrition Examination Survey VI that measured serum TSH, FT4, and thyroid peroxidase antibody from 7,061 individuals (urinary iodine measurement in 6,565). Age- and gender-specific reference intervals were established from 95% confidence limits from the 2.5 to 97.5 percentile of TSH (log-transformed) and FT4 in reference populations.ResultsThe geometric mean of TSH was 2.16 ± 0.01 mIU/L, with the lowest value found in the middle aged group (2.04 ± 0.02 mIU/L) and higher values noted in age groups of 10–19 and over 70 years (2.38 ± 0.02 and 2.32 ± 0.07 mIU/L, respectively). The association of TSH and age was U-shaped. The overall reference interval of TSH was 0.59–7.03 mIU/L. Mean FT4 was 1.25 ± 0.003 ng/dL (16.09 ± 0.039 pmol/L), and it showed a small but continuous decrease after 20 years of age (P < 0.001). There was a significant positive correlation between TSH and urine iodine concentration (r = 0.154, P < 0.001).ConclusionsThe reference interval of TSH in Korea, where iodine intake is above the requirement, was 0.59–7.03 mIU/L and showed U-shaped change with age, which was a similar pattern to iodine intake. The reference interval of FT4 was 0.92–1.60 ng/dL. The geometric mean and upper limit of TSH were higher than those of Western populations, reflecting the paramount importance of iodine intake on thyroid function.

Thyroid Function and the Risk of Atherosclerotic Cardiovascular Morbidity and Mortality: The Rotterdam Study.

Thyroid hormones have been linked with various proatherogenic and antiatherogenic processes. However, the relationship of thyroid function with manifestations of atherosclerosis remains unclear. To investigate the association of thyroid function with atherosclerosis throughout its spectrum; that is, subclinical atherosclerosis, incident atherosclerotic cardiovascular (ASCV) events, and ASCV mortality. This population-based study was embedded within the Rotterdam Study. The risk of atherosclerosis was evaluated by measuring (1) presence of subclinical atherosclerosis, assessed by coronary artery calcification score >100 AU; (2) ASCV events, defined as fatal and nonfatal myocardial infarction, other coronary heart disease mortality, or stroke; (3) ASCV mortality, defined as death because of coronary heart disease and cerebrovascular or other atherosclerotic diseases. Associations of thyroid-stimulating hormone and free thyroxine with the outcomes were assessed through logistic regression and Cox proportional hazard models, adjusted for potential confounders, including cardiovascular risk factors. A total of 9420 community-dwelling participants (mean age±SD, 64.8±9.7 years) were included. During a median follow-up of 8.8 years (interquartile range, 4.5-11.8 years), 934 incident ASCV events and 612 ASCV deaths occurred. Free thyroxine levels were positively associated with high coronary artery calcification score (odds ratio, 2.28; 95% confidence interval, 1.30-4.02) and incident ASCV events (hazard ratio, 1.87; confidence interval, 1.34-2.59). The risk of ASCV mortality increased in a linear manner with higher free thyroxine levels (hazard ratio, 2.41; confidence interval, 1.68-3.47 per 1 ng/dL) and lower thyroid-stimulating hormone levels (hazard ratio, 0.92; confidence interval, 0.84-1.00 per 1 logTSH). Results remained similar or became stronger among euthyroid participants. Free thyroxine levels in middle-aged and elderly subjects were positively associated with atherosclerosis throughout the whole disease spectrum, independent of cardiovascular risk factors.

Association of TSH With Cardiovascular Disease Risk in Overweight and Obese Children During Lifestyle Intervention.

Overweight and obese children have an increased risk to develop cardiovascular diseases (CVDs) in which thyroid-stimulating hormone (TSH) has been suggested as an intermediary factor. However, results of cross-sectional studies are inconclusive, and intervention studies investigating changes in TSH concentrations in association with changes in cardiovascular risk parameters in overweight and obese children are scarce. To gain insight in associations of circulating TSH concentrations and cardiovascular risk parameters in overweight and obese children. Nonrandomized lifestyle intervention. Centre for Overweight Adolescent and Children's Healthcare. Three hundred thirty euthyroid overweight and obese children. Long-term lifestyle intervention. TSH concentrations, pituitary TSH release in response to thyrotropin-releasing hormone (TRH), and cardiovascular risk parameters. At baseline, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), and monocyte chemotactic protein 1 concentrations were significantly associated with serum TSH concentrations. TSH release by the pituitary in response to exogenous TRH was not associated with cardiovascular risk parameters. During lifestyle intervention, several cardiovascular risk parameters significantly improved. In children whose body mass index z score improved, changes in TSH concentrations were significantly associated with changes in TC, LDL-C, and TAG concentrations. In euthyroid overweight and obese children, circulating TSH concentrations are positively associated with markers representing increased CVD risk. Changes in TSH concentrations are also associated with changes in lipid concentrations in children with successful weight loss, which is consistent with TSH being an intermediary factor in modulating lipid and lipoprotein metabolism.

Association of thyroid-stimulating hormone with lipid concentrations: an 11-year longitudinal study.

Scant data exist on the longitudinal association between thyroid function and lipid concentrations. We investigated associations of TSH and lipid concentrations cross-sectionally and longitudinally in a nationwide population sample. A total of 5205 randomly sampled participants representative of Finns aged ≥30 years were examined in 2000-2001 and included in cross-sectional analyses. A total of 2486 were re-examined 11 years later and included in longitudinal analyses. With linear regression models adjusted for age, gender, smoking and body mass index, we assessed the associations of baseline TSH and TSH categories (low, reference range and high) with total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol; apolipoprotein A1 and B; and triglycerides at baseline and follow-up. At baseline, higher TSH associated with higher total cholesterol (β = 0·025, standard error [SE] = 0·007, P < 0·001), LDL cholesterol (β = 0·020, SE = 0·007, P = 0·002), apolipoprotein B (β = 0·006, SE = 0·002, P < 0·001) and log triglycerides (β = 0·008, SE = 0·003, P = 0·004), but not with other lipid outcomes. Higher baseline TSH associated with higher total cholesterol (β = 0·056, SE = 0·026, P = 0·033), LDL cholesterol (β = 0·057, SE = 0·023, P = 0·015) and apolipoprotein B (β = 0·012, SE = 0·006, P = 0·028) at follow-up in women, but not with any lipid outcomes in men. Participants with high TSH at baseline had a 0·22 mmol/l (95% confidence interval 0·02-0·41 mmol/l) higher LDL cholesterol at follow-up (P = 0·028) than participants with TSH in the reference range (0·4-3·4 mU/l). However, exclusion of participants with high-risk baseline lipid values rendered these positive longitudinal associations nonsignificant (P ≥ 0·098). We could confirm a modest association between higher TSH and an adverse lipid profile cross-sectionally but not indisputably longitudinally.

Higher Plasma ApoE Levels are Associated with Low-Normal Thyroid Function: Studies in Diabetic and Nondiabetic Subjects.

Low-normal thyroid function within the euthyroid range may confer higher plasma triglycerides, but relationships with plasma apolipoprotein (apo) E, which plays an important role in the metabolism of triglyceride-rich apoB-containing lipoproteins, are unknown. We determined relationships of plasma apoE with thyroid stimulating hormone (TSH) and free thyroxine (free T4) in euthyroid subjects with and without Type 2 diabetes mellitus (T2DM). TSH, free T4, lipids, and apoE were measured in fasting plasma from 72 T2DM subjects and 82 nondiabetic subjects. The APOE genotype was also determined. Free T4 was slightly higher in T2DM (p=0.030), but TSH levels were not different vs. nondiabetic subjects. The APOE genotype distribution was not different between the groups. None of the participants had the ε2/ε2 genotype. Plasma triglycerides were higher in T2DM (p=0.037). ApoB and apoE levels were not different between the groups. In all subjects combined, multivariable analysis showed that plasma triglycerides (p=0.039), non-high density lipoprotein (non-HDL) cholesterol (p=0.030), and apoE levels (p=0.002) were each independently and positively associated with TSH after adjustment for age, sex, T2DM and the presence of the APOE ε3 allele. Furthermore, the associations of TSH with apoE remained present after adjustment for either triglycerides, non-HDL cholesterol, or apoB (p=0.005 to 0.023). The presence of T2DM did not modify the relationships of TSH with these (apo) lipoprotein variables (p=0.11 to 0.36). In conclusion, low-normal thyroid function, as indicated by higher TSH levels within the euthyroid range, may influence the metabolism of triglyceride-rich lipoproteins by affecting apoE regulation.

Association of Thyroid-Stimulating Hormone with Resting Energy Expenditure in Euthyroid Elderly Subjects: A Cross-Sectional Study

Background: Several studies have reported positive correlations between thyroid-stimulating hormone (TSH) and body mass index (BMI) in euthyroid subjects. As impaired thyroid function is known to affect the metabolic rate, this study investigated whether TSH is associated with resting energy expenditure (REE) in euthyroid elderly subjects, independent of age, anthropometric data and body composition. Methods: Cross-sectional data of 77 women (66-96 years, BMI 18-36 kg/m²) and 55 men (66-86 years, BMI 20-39 kg/m²) were analyzed. REE was measured using indirect calorimetry, body composition by bioelectrical impedance analysis and serum TSH using an electrochemiluminescence immunoassay. Results: REE, fat-free mass (FFM) and waist circumference (WC) were significantly lower, whereas TSH and fat mass (FM) were significantly higher in women than in men. In multiple stepwise regression analysis, with age-adjusted REE (REE_adj) as the dependent variable and FFM, FM and WC as independent variables, FFM and WC explained 40.7% in women and FFM 32.8% in men of the variability in REE_adj. Including TSH in the model led to a significant rise of the adjusted R-squared value in women only, and explained an additional 2.8% of the variability in REE_adj. Conclusions: TSH is independently and negatively associated with REE in euthyroid elderly women.

Association of thyroid-stimulating hormone and cardiovascular risk factors.

Thyroid hormone plays an important role in regulating the lipid and glucose metabolism. Previously, much attention has been drawn to define the pathophysiological relationship between thyroid dysfunction and the incidence of cardiovascular diseases (CVDs). While the conditions of overt hypothyroidism and subclinical hypothyroidism were both emphasized, the association between CVD risks and the deregulated circulating thyroid-stimulating hormone (TSH) level remains to be elucidated. Nevertheless, multiple TSH-mediated physiological adaptations, including alteration of the serum lipids, body mass index, blood pressure and insulin sensitivity, have led to the difficulty of clearly examining the association between the TSH level and CVD prevalence. The current review aims to 1) summarize the evidence for the role of thyroid dysfunction and TSH abnormality in CVD pathogenesis and 2) explore the possible underlying molecular mechanisms of TSH-mediated cardiovascular pathology in hopes of providing better therapeutic strategies for the patients with deregulated TSH.

Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?

The relationship between overt hypothyroidism and cardiovascular risk has been well documented and some data also suggest an association between cardiovascular risk and subclinical hypothyroidism. The aim of our study was to investigate, in a large cohort of euthyroid women, the association of thyroid stimulating hormone (TSH) within the normal reference range with cardiovascular risk factors. The study was carried out on 744 women with normal thyroid function (TSH 0.3-4.9 μU/mL). Women with TSH above the median (≥2.1 μU/mL) were more obese, had greater waist girth, were more hypertensive and had higher levels of total cholesterol (TC), serum triglycerides (TG), blood sugar (BG) and lower levels of HDL-cholesterol (HDL-C) than women with TSH below the median. TSH was significantly correlated with body mass index (BMI), waist circumference, BG, TG, TC, HDL-C and hypertension. Multiple backward stepwise regression analysis with age, waist circumference and TSH as independent variables confirmed the strong association of TSH with BG, TG, HDL-C and hypertension. A total of 205 patients (28%) fulfilled the definition criteria of the metabolic syndrome and the prevalence of metabolic syndrome was significantly greater in patients with TSH above than in patients with TSH below the median. Results of logistic analysis, including age and TSH as predictor variables, confirmed the association of TSH with metabolic syndrome.The results of this study suggest that TSH in the upper limits of the reference range (above 2.1 μU/ml) is associated with a less favourable cardiometabolic profile and consequently with a higher risk of developing cardiovascular diseases.

Thyroid function in the people with obesity

The aim of this study is to identify the association of thyroid stimulating hormone and thyroxin levels with body mass index (BMI) and waste circumference in men and women with overweight and obesity. Current study was performed within the HAPIEE. The sample of 280 subjects (125 men (44.6%) and 155 women (55.4%)) was analyzed. Thyroid stimulating hormone level was high in integrated subsample with II and III obesity degree (body mass index ≥35 kg/m2). Average levels of general thyroxin were significantly higher in abdominal obese women with body mass index ≥30 (according to NCEP-АТР III, 2001), than in subjects with normal weight and overweight. Significant decrease of general thyroxin was detected in men with gross obesity (body mass index ≥35 kg/m2). In comparison with men women have positive correlation between general thyroxin level and waist circumference.

Serum TSH Level in Healthy Koreans and the Association of TSH with Serum Lipid Concentration and Metabolic Syndrome

Background/AimsThe proper treatment of subclinical hypothyroidism and the normal range of serum thyroid stimulating hormone (TSH) concentration are intensely debated. However, few reports have investigated TSH concentrations in Asian ethnic groups. Therefore, the present study was designed to define the TSH reference range in a Korean population and to investigate the metabolic significance of TSH concentration.MethodsWe enrolled patients who underwent medical examination at the CHA Bundang Medical Center. Anthropometric data were evaluated, and serum TSH, free T4, and lipid profiles were assayed.ResultsA total of 7,270 subjects were included. Mean TSH concentration of the study population was 1.82 ± 0.95 mU/L, and we observed a sex-related difference in TSH concentration (male, 1.67 ± 0.87 mU/L; female, 2.02 ± 1.01 mU/L; p < 0.01). When the 2.5 and 97.5 percentiles were calculated, 95% TSH reference limits were 0.52-4.29 mU/L. TSH concentration was higher in elderly subjects, during winter, in postmenopausal women, and in obese males. Moreover, TSH showed significantly positive correlations with serum total cholesterol, triglyceride, and low density lipoprotein cholesterol regardless of sex, age, season, obesity, or menopausal status (all p < 0.01). Finally, TSH concentration was positively related to the prevalence of metabolic syndrome.ConclusionsWe demonstrated the association between TSH concentration within the normal reference range and serum lipid levels. TSH concentration varies according to sex, age, season, and body mass index (only in males). Moreover, high normal TSH levels were significantly associated with an increased prevalence of metabolic syndrome, which may be of importance when evaluating subjects with high normal TSH concentration.

Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS

There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic parameters. Little information is available regarding this relationship in women with polycystic ovary syndrome. However all those pathologies are also described as often affecting women with polycystic ovary syndrome. The association between thyroid-stimulating hormone <2.5 mIU/l and ≥2.5 mIU/l with insulin resistance and endocrine parameters in 103 women with polycystic ovary syndrome was studied. Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed with calculation of insulin resistance indices. Women with thyroid-stimulating hormone ≥2.5 mIU/l had a significantly higher body mass index ( P = 0.003), higher fasting insulin concentrations ( P = 0.02) and altered insulin resistance indices ( P = 0.007), higher total testosterone ( P = 0.009) and free androgen indices ( P = 0.001) and decreased sex hormone–binding globulin concentrations ( P = 0.01) in comparison with women with thyroid-stimulating hormone <2.5 mIU/l. Generally, all of these parameters correlated significantly ( P < 0.05) with thyroid-stimulating hormone only in women with thyroid-stimulating hormone ≥2.5 mIU/l. Women with polycystic ovary syndrome and with thyroid-stimulating hormone ≥2.5 mIU/l had significantly altered endocrine and metabolic changes.

Association of thyroid stimulating hormone and coronary lipid risk factors with lipid peroxidation in hypothyroidism

Hypothyroidism is the second most prevalent disorder in India and most cases require lifelong treatment. Disordered myocardial function is one of the complications of overt hypothyroidism. Dyslipidemia and lipid peroxidation are two biochemical derangements of hypothyroidism and both have been found to be associated. Still uncertainty remains regarding the origin of lipid peroxidation in this clinical condition. Besides, thyroid stimulating hormone or thyrotropin at a higher concentration can induce secretion of inflammatory cytokines and decrease the antioxidant status. Hence, we analyzed the association of lipid risk factors and thyrotropin in hypothyroidism with the extent of lipid peroxidation. A total of 42 primary hypothyroid patients volunteered to give fasting blood samples prior to therapy for the analysis of oxidative stress, thyroid and lipid profiles. Oxidative stress was confirmed by the increased levels of malondialdehyde and protein carbonylation and decreased levels of reduced glutathione. Simple correlation analyses revealed the association of lipid peroxidation with both thyrotropin and lipid risk factors. Partial correlation analyses showed that thyrotropin and lipid risk factors mutually influence their association with the higher malondialdehyde levels in these patients. Hyperthyrotropinemia may be considered not only as an index of the severity of hypothyroidism but also of the extent of the associated lipid peroxidation.

Associations of Thyroid-Stimulating Hormone and Free Thyroxine Concentrations with Health and Life Satisfaction in Elderly Adults

To analyze associations between thyroid-stimulating hormone (TSH) and free thyroxine (FT4 concentrations and life satisfaction, symptoms, self-rated health, and common neuropsychiatric diseases (depression or dementia) in a community-dwelling elderly population to provide evidence whether to decrease the upper reference limit for TSH or the optimal TSH target in levothyroxine treatment in older adults. In this cross-sectional study, we determined TSH and FT4 concentrations in a thyroid disease-free population of 502 men (median age, 71 years) and 584 women (median age, 73 years) and in a patient group of 49 women (median age, 75 years) with primary hypothyroidism who were stable users of thyroxine treatment. Life satisfaction, self-rated health, depression, and dementia were assessed with specific questions and with tools such as the Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH and FT4 levels were assessed in the thyroid disease-free population. Levels of TSH and FT4 in thyroid disease-free women and in women treated with thyroxine were also compared. After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most symptoms in the thyroid disease-free population. No associations were found between diagnosed depression or Mini-Mental State Examination results and levels of TSH and FT4. Dementia was associated with higher FT4 concentration in men. Although women treated with thyroxine had TSH levels that were higher than thyroid disease-free women, there were no statistically significant differences in independent variables between these 2 groups. Our results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines.