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Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

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Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS. This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight management clinic from 2/1/2013-2/1/2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A1C, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed. A total of 3,447 patients, 75.6% female and 38% African-American, without known thyroid dysfunction were included. Mean±SD age was 46.74±15.11 years and mean±SD BMI was 36.06±9.89kg/m(2). Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41μIU/mL compared to 1.36μIU/mL in patients without MetS (p=0.45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS. Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.
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Original Article EP15739.OR
THYROID FUNCTION AND METABOLIC SYNDROME: A CROSS-SECTIONAL STUDY IN OBESE AND
OVERWEIGHT PATIENTS.
Swetha Kommareddy MD, Sun Y. Lee MD, Lewis E Braverman MD,
Elizabeth N. Pearce MD, MSc.
Running title: TSH and metabolic syndrome
From: Section of Endocrinology, Diabetes, and Nutrition, Boston University School of
Medicine, Boston, MA
Correspondence address: Dr. Elizabeth N Pearce,
Section of Endocrinology, Diabetes and Nutrition,
Boston University School of Medicine,
88 East Newton Street, H3600, Boston, MA-02118.
Email: elizabeth.pearce@bmc.org.
DOI:10.4158/EP15739.OR
© 2015 AACE.
Disclosures: The authors have no conflict of interest.
Word count: 2,675 (not including abstract)
Keywords: Thyroid function; Metabolic Syndrome; Obese; Overweight
DOI:10.4158/EP15739.OR
© 2015 AACE.
Abstract
Objective:
Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular
disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In
obese patients, serum thyroid stimulating hormone (TSH) levels tend to be higher than in lean
controls. The objective of this study was to assess potential associations between serum TSH
levels and MetS as well as individual components of MetS.
Methods:
This was a cross-sectional observational study of obese and overweight patients seen for initial
evaluation at the Boston Medical Center weight management clinic from 2/1/2013-2/1/2014.
Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose,
hemoglobin A1C, and lipid levels were obtained from electronic medical records. Associations
between serum TSH levels and presence of MetS and its components were assessed.
Results:
A total of 3,447 patients, 75.6% female and 38% African-American, without known thyroid
dysfunction were included. Mean±SD age was 46.74±15.11years and mean±SD BMI was 36.06±
9.89kg/m2. Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In
patients with MetS, the median serum TSH was 1.41μIU/mL compared to 1.36μIU/mL in
patients without MetS (p=0.45). In multivariate models, there was no significant association
between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education,
socioeconomic status, and smoking. There were also no significant associations between serum
TSH and individual components of the MetS.
Conclusions:
Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and
overweight individuals.
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Abbreviations:
MetS = metabolic syndrome; TSH = thyroid stimulating hormone; SD = standard deviation;
NCEP = National Cholesterol Education program; ATP III = Adult Treatment Panel III;
HDL-C = high density lipoprotein cholesterol; LDL-C = low density lipoprotein cholesterol;
BMI = body mass index; FT3 = free thyroxine; TRH = thyroid releasing hormone;
T4 = thyroxine; T3 = triiodothyronine; TR = thyroid receptor; FT4 = free thyroxine;
Hgb A1c = hemoglobin A1c; HOMA-IR = homeostasis model of insulin resistance;
SBP = Systolic blood pressure; DBP = diastolic blood pressure.
Introduction
Metabolic syndrome (MetS) is a cluster of modifiable risk factors associated with an
increased risk of developing cardiovascular disease and type 2 diabetes [1]. The National
Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) guidelines define
metabolic syndrome as having three out of the five following modifiable risk factors: abdominal
obesity, low high density lipoprotein cholesterol (HDL-C) concentration, elevated serum
triglycerides, hypertension, and insulin resistance [2]. MetS has been linked with obesity and is
mainly mediated by insulin resistance [3]. Individuals with metabolic syndrome should be
identified early so that their cardiovascular risk factors can be modified [4].
Hypothyroidism is also a known cardiovascular risk factor, mediated at least in part by its
effects on lipid metabolism and blood pressure [5–7] along with various other mechanisms [8].
Observational studies have shown inconsistent associations between subclinical hypothyroidism
and dyslipidemia [9]. The HUNT study, a cross-sectional, population-based study of 30,656
participants, showed that higher thyroid stimulating hormone (TSH) levels within the euthyroid
range were associated with higher total cholesterol, higher low density lipoprotein cholesterol
(LDL-C) and triglycerides, and lower HDL-C levels [7]. Some studies have also shown insulin
resistance to be related to thyroid function [10], but the data are conflicting. In meta-analyses,
higher TSH levels have been associated with increased cardiovascular events and mortality [11–
13].
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Serum TSH levels tend to be higher in euthyroid obese patients compared to euthyroid
lean controls. In a cross-sectional analysis of National Health and Nutrition Examination Survey
(NHANES) 2007-2008 data, body mass index (BMI) and waist circumference were positively
correlated with serum TSH and free triiodothyronine (FT3) levels [14]. Elevated TSH and FT3
levels in obese individuals are thought to be due to various mechanisms which include leptin-
mediated effects on thyroid releasing hormone (TRH) gene expression in the paraventricular
nucleus stimulating TSH release [15], enhanced peripheral conversion of thyroxine (T4) to
triiodothyronine (T3) due to high caloric intake [16], decreased negative feedback due to
partially bio-inactive TSH at the level of hypothalamus-pituitary axis, decreased thyroid
receptors (TR) and TSH receptors, and neuroendocrine dysfunction [17–19].
Many studies have assessed the associations between thyroid dysfunction and one or
more individual components of the metabolic syndrome. These cross sectional studies have
shown variable correlations between serum TSH, free thyroxine (FT4) and serum T3 values and
components of the MetS [20,21]. In a cross-sectional study by Roos et al., FT4 was associated
with four of the five components of the metabolic syndrome [22].
A few of these studies also showed increased prevalence of MetS with increasing serum
TSH level [23,24]. These studies suggest increased risk of metabolic syndrome with elevated
serum TSH levels. However, some studies were done only in certain age groups, ethnicities, or
genders. None of these studies specifically evaluated the association between thyroid function
and metabolic syndrome in obese and overweight patients. The aim of our study was to
determine the associations between serum TSH levels and MetS as well as its individual
components in obese and overweight individuals.
Methods
We conducted a cross-sectional, observational study of obese and overweight patients
seen for initial evaluation at the Boston Medical Center weight management clinic between
February 1, 2013 and February 1, 2014. The study protocol was approved by the Institutional
Review Board of the Boston University Medical Campus and Boston Medical Center, Boston,
MA.
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Study population:
A total of 3,447 consecutive patients seen at the Boston Medical Center weight
management clinic between 2/1/2013 and 2/1/2014 who were 18 years with BMI 25.0 kg/m2
without known thyroid dysfunction were identified from electronic medical records for inclusion
in the study. We excluded patients taking anti-thyroid medications, thyroid hormone
replacement, or lithium, or amiodarone. We also excluded patients who did not have a serum
TSH level checked within 30 days of their initial visit to the weight management clinic.
Data collection:
Demographic, laboratory, and anthropometric data obtained during a routine clinical visit
were collected. Patients’ self-reported smoking status (current, past or never), and demographic
information including age, gender, self-reported race/ethnicity as defined by the United States
Office of Management and Budget, highest education level, and insurance type (as a surrogate
for socio-economic status) were obtained from the electronic medical records. Laboratory data
collected from medical records included serum TSH levels, serum insulin levels, serum glucose
levels, hemoglobin A1C (HgbA1c), and serum lipid concentrations. Whether blood draws were
fasting or not was not specified in the medical records. Therefore, we arbitrarily determined that
measurements obtained prior to 9:00 AM were fasting. Waist circumference, BMI, blood
pressure, and medication list including diabetes medications, antihypertensives, and statins from
the initial clinical visit were assessed.
For study purposes, metabolic syndrome was defined as meeting any three of the
following five criteria as outlined by the NCEP ATP III [2]: 1) waist circumference 40 inches
in men or 35 inches in women; 2) serum triglycerides 150 mg/dL or on drug treatment for
elevated triglycerides (gemfibrozil, fenofibrate); 3) serum HDL-C <40 mg/dL in men or <50
mg/dL in women; 4) blood pressure 130/85 mmHg or on antihypertensive treatment; 5) fasting
plasma glucose 100 mg/dL, on drug treatment for elevated blood glucose, history of type 2
diabetes, or HgbA1c 5.7%. Insulin resistance was assessed at baseline using the homeostasis
model of insulin resistance (HOMA-IR), calculated as fasting insulin (µU/mL) × fasting glucose
(mmol/L)/22.5 [25].
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Statistical Analyses:
Statistical analyses were performed using SAS software, version 9.3 (SAS institute, Cary,
NC).
Descriptive statistics were reported as mean ± SD or median (range), as appropriate.
Chi-square tests were used to compare the distribution of categorical demographic
variables between patients with MetS and those without MetS. Wilcoxon Rank Sum Tests were
used to compare the median values of age, waist circumference, systolic blood pressure (SBP),
diastolic blood pressure (DBP), TSH, HgbA1c, and HDL-C between patients with MetS and
those without MetS.
Multivariate logistic regression analysis was performed to assess for a potential
association between MetS as a dichotomous outcome and serum TSH as a continuous predictor,
adjusting for the following covariates: age, gender, self-reported race/ethnicity as defined by the
United States Office of Management and Budget, smoking status, highest education level, and
type of insurance. Multivariate logistic regression analyses were also used to determine the
potential associations between each of the individual components of MetS as a dichotomous
outcome and serum TSH as a continuous variable, adjusting for the same covariates.
Stratified analyses using multivariate logistic regression were also performed to assess
potential associations between TSH and MetS and its individual components, adjusting for the
covariates mentioned above. The analyses were done stratified by gender, TSH categories based
on normal TSH ranges, and BMI categories. TSH categories were defined as follows: TSH <
0.35µIU/mL, 0.35-2.49µIU/mL, 2.5-5µIU/mL, and > 5µIU/mL. BMI categories were defined as
follows: BMI < 25kg/m2, 25-29kg/m2, 30-34kg/m2, 35-39kg/m2, and 40kg/m2.
Sensitivity analysis was performed using the multivariate logistic regression analysis of
MetS and TSH, adjusted for the covariates mentioned above, for only those with TSH in normal
ranges (0.35-5.5µIU/mL).
Finally, TSH was divided into quartiles based on the distribution of TSH values in our
sample population: TSH < 0.85µIU/mL, 0.85-1.29µIU/mL, 1.3-1.94µIU/mL, and 1.95µIU/mL.
The multivariate logistic regression analyses were performed to assess for associations between
MetS and TSH quartiles, adjusting for the covariates mentioned above.
A two-tailed p value of < 0.05 was considered significant.
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Results
A total of 3,447 patients initially qualified for study inclusion. Demographic data for the
sample population are shown in Table 1. Of 3,447 individuals, 878 patients were defined as
overweight (BMI 25-29 kg/m2) and 2,561 patients were defined as obese (BMI 30 kg/m2). The
median (range) TSH values of overweight patients was 1.20 µIU/mL (0.01-65.75 µIU/mL), and
of obese patients 1.33 µIU/mL (0.01-60.32 µIU/mL).
Of 3,447 individuals, 1,005 patients had adequate data to determine the presence of MetS
for the primary analysis. Among these 1,005 patients, the prevalence of MetS was 71.8%.
Patients with MetS were more likely to be women (73.0%), African American and non-smokers
(Table 2). Fifty five patients (1.60%) had a serum TSH > 5 µIU/ml, and among them 20
patients (0.58%) had values > 10 µIU/ml.
TSH and metabolic syndrome:
The median serum TSH was 1.41 μIU/mL in patients with MetS and 1.36 μIU/mL in
patients without MetS (p=0.45). In adjusted multivariable models, there was no significant
association between serum TSH level and the presence of MetS (β-coefficient 0.093, SE 0.1227,
p-value 0.45) (Table 3).
TSH and individual components of metabolic syndrome in the 3,447 patients:
A total of 1,993 patients were hypertensive according to study criteria. We found no
significant association between TSH and the presence of hypertension (β-coefficient -0.0294, SE
0.0245, p-value 0.23). A total of 871 patients had high triglyceride levels and a total of 861
patients had low HDL-C levels. There were no significant associations between TSH and HDL-C
or triglyceride levels (HDL-C: β-coefficient 0.0425, SE 0.0778, P-value 0.58; triglyceride: β-
coefficient 0.1082, SE 0.0841, p-value 0.20). Among the 1,504 subjects with insulin resistance
data, there was no significant association between serum TSH and insulin resistance (β-
coefficient 0.1166, SE 0.0618, p-value 0.06). A total of 382 patients had waist circumference
recorded; among these patients, we found no association between serum TSH and waist
circumference (β-coefficient 0.6183, SE 0.4534, p-value 0.17). Given the relatively small
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number of patients with waist circumference recorded, we performed a sensitivity analysis
categorizing those with missing waist circumference but with two other qualifying components
of MetS as having MetS. The sensitivity analysis yielded the same primary outcome of no
statistically significant association between TSH and the presence of MetS (β-coefficient 0.043,
SE 0.0830, p-value 0.60).
Prevalence of metabolic syndrome and its individual components by TSH category
(Figure 1):
There was no significant differences in the prevalence of MetS among TSH categories
(p=0.05). There were no significant difference in the prevalence of hypertension (p=0.87),
increased waist circumference (p=0.62) or low HDL-C (p=0.23) among TSH category. High
triglyceride level was most prevalent in TSH < 0.35 µIU/ml category and least prevalent in TSH
0.35-2.5µIU/ml category. The difference in the prevalence of high triglyceride levels among the
TSH categories was significant (p=0.0004). Insulin resistance was most prevalent in TSH 2.5-5
µIU/ml category and least prevalent in TSH >5 µIU/ml category. There was a significant
difference in the prevalence of insulin resistance by TSH category (p=0.03).
TSH quartiles and metabolic syndrome and its components:
There was no significant association between TSH quartiles and MetS in adjusted
multivariable models (β-coefficient 0.0374, SE 0.1038, p-value 0.72). Similarly, we did not find
any significant associations between TSH quartiles and the individual components of the MetS in
multivariable models adjusted for age, sex, race, education, insurance type and smoking status.
Stratified analyses:
In multivariate analyses stratified by gender, MetS was not significantly associated with
TSH in either men or women (men: β-coefficient 0.0405, SE 0.1028, p-value 0.69; women: β-
coefficient 0.1497, SE 0.1316, p-value 0.26). Similarly, there were no associations between
MetS and TSH levels and its components when analyses were stratified by BMI category (data
not shown).
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Discussion:
We did not find a significant association between serum TSH concentrations and the
prevalence of metabolic syndrome in this cross-sectional study of obese and overweight
individuals.
Results of previous cross-sectional studies examining the associations between thyroid
function and metabolic syndrome have been inconsistent. In The Health Aging and Body
Composition Study, it was shown that each one-unit increase in serum TSH concentrations
within the euthyroid range increased the odds of having MetS by 18% [23]. The results remained
unchanged when adjusted for BMI. This study included older adults aged 70-79 years who had a
higher prevalence of subclinical hypothyroidism than was observed in the present study. In two
studies of euthyroid post-menopausal women in Korea, higher serum TSH values within the
euthyroid range was associated with increasing prevalence of MetS [24,26]. Ruhla et al. reported
a higher likelihood of metabolic syndrome in individuals with TSH in the upper normal range
(2.5- 4.5 µIU/L) when compared to those with low-normal TSH (0.3-2.5 µIU/L), after adjusting
for age and sex [27]. In their study, higher TSH levels were positively correlated with BMI, and
individuals with high-normal serum TSH concentrations were more obese. Their study had a
younger patient population, with lower TSH values than those seen in The Health Aging and
Body Composition Study. In contrast, a cross-sectional study of a Hispanic population by
Garduno-Garcia et al. showed no difference in the prevalence of metabolic syndrome between
euthyroid and subclinical hypothyroid participants [20]. The differing results in our study could
have been due to variations in the definitions used to categorize MetS and thyroid status,
differences in study populations, and differences in sample size. Also it should be noted that
some studies had a higher prevalence of subclinical hypothyroidism (up to 13%), and the
association between TSH and prevalent MetS became more significant only at TSH > 10 µIU/ml
[23], whereas in our study, fewer patients (1.6%) had TSH values > 5 µIU/ml.
We also failed to identify an association between serum TSH levels and the individual
components of the metabolic syndrome. Previously, studies have shown an association between
thyroid function and body weight [14,19]. In the study by Garduno-Garcia et al., FT4 was
inversely related with insulin resistance, and serum TSH positively correlated with total
cholesterol, triglycerides and waist circumference [20]. However, another study of older adults
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did not find an association between thyroid function and waist circumference, similar to our
results [23]. An association between thyroid dysfunction and blood pressure has been reported in
several studies and is thought to be mediated by increased arterial stiffness [6]. Ittermann et al.
reported such an association in children and adolescents [28]. A recent cross-sectional cohort
study also noted an association between FT4 and arterial stiffness [29]. The HUNT study showed
a linear association between TSH levels and blood pressure [6]. However, this association was
not seen in another study evaluating the relation between thyroid function and components of the
MetS [23]. To date, many published studies have indicated an association between thyroid
function and dyslipidemia [9]. In studies which have evaluated the relationship between thyroid
function and MetS, the strongest association was seen with the high triglyceride component of
the MetS. The HUNT study also showed that higher TSH levels correlated with higher
triglyceride and lower HDL-C concentrations and this association became more significant in
participants with BMI 25 kg/m2 [7]. In a Dutch population-based study of 2,703 participants,
FT4 was inversely associated with total cholesterol, LDL-C, triglycerides, and insulin resistance
after adjustment for age and sex [22]. In our study we did not see an association between serum
TSH level and triglyceride or HDL-C concentrations. Finally, even though insulin resistance is
thought to be the underlying process of MetS, we did not find an association between TSH level
and insulin resistance. This could have been due to potential misclassification of serum lipid,
glucose, and insulin levels as fasting samples in our study.
The strengths of our study include the relatively large sample size in a single institution
and adjustments for multiple covariates. Our study has several limitations. As TSH was
measured only once and serum FT4 levels were not available, we were unable to distinguish
between overt and subclinical hypothyroidism. Thus, we were unable to analyze associations
between FT4 and individual components of metabolic syndrome as was done in previous studies.
Due to retrospective nature of the study, we assumed that patients on antihypertensive, lipid-
lowering, or diabetic medications indeed had these components of metabolic syndrome. Fasting
samples were determined based on time of lab draw, which might have led to some
misclassifications of lipid concentrations, serum insulin, and serum glucose levels.
In conclusion, we did not observe any significant associations between serum TSH levels
and prevalence of metabolic syndrome or individual components of the metabolic syndrome in
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obese and overweight individuals. To date, there is no data to suggest that treating high-normal
serum TSH levels to lower values has any beneficial effect on cardiovascular risk in these
individuals. Prospective studies are needed to determine whether treating high-normal TSH
values can improve metabolic parameters.
Acknowledgments:
Abstract and the results of this study were presented as a poster at the 84th Annual Meeting of
American Thyroid Association in October 29 – November 2, 2014, Coronado, CA.
This research was supported in part by NIH T32DK007201-37 (SYL).
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MetS = metabolic syndrome, HDL-C = high density lipoprotein cholesterol, TSH = thyroid
stimulating hormone
92%
71% 79%
56%
0%
20%
40%
60%
80%
100%
< 0.35 шϬ͘ϯϱƚŽ
чϮ͘ϱ
>2.5 to
чϱ
> 5
Percentage positives
Serum TSH levels (μIU/mL)
Metabolic syndrome
(p = 0.05)
69% 67% 66% 64%
0%
20%
40%
60%
80%
100%
< 0.35 шϬ͘ϯϱƚŽ
чϮ͘ϱ
>2.5 to
чϱ
> 5
Percentage positives
Serum TSH levels (μIU/mL)
Hypertension
(p = 0.87)
100% 97% 99% 100%
0%
20%
40%
60%
80%
100%
< 0.35 шϬ͘ϯϱƚŽ
чϮ͘ϱ
>2.5 to
чϱ
> 5
Percentage positives
Serum TSH levels (μIU/mL)
Waist circumference
(p = 0.62)
83%
61% 62% 70%
0%
20%
40%
60%
80%
100%
< 0.35 шϬ͘ϯϱ ƚŽ
чϮ͘ϱ
>2.5 to
чϱ
> 5
Percentage positives
Serum TSH levels (μIU/mL)
Low HDL-C
(p = 0.23)
68%
37% 45% 53%
0%
20%
40%
60%
80%
100%
< 0.35 шϬ͘ϯϱƚŽ
чϮ͘ϱ
>2.5 to
чϱ
> 5
Percentage positives
Serum TSH levels (μIU/mL)
High Triglycerides
(p = 0.0004)
73% 66% 74%
64%
0%
20%
40%
60%
80%
100%
< 0.35 шϬ͘ϯϱƚŽ
чϮ͘ϱ
>2.5 to
чϱ
> 5
Percentage positives
Serum TSH levels (μIU/mL)
Insulin resistance
(p = 0.03)
Figure.1. Prevalence of metabolic syndrome and its individual components (hypertension,
waist circumference, low HDL-C, high triglycerides and insulin resistance) within each TSH
categories.
Table 1. Demographic characteristics of study cohort (n=3447)
n (%)
Gender Male 839 (24.3)
Female 2608 (75.7)
Race/Ethnicity White 787 (23.6)
African American 1272 (38.1)
Hispanic 840 (25.2)
Asian 64 (1.9)
Middle Eastern 41 (1.2)
Not Available/Other 336 (10.1)
Highest education
level
8t
h
grade or less 334 (11.6)
Some High school/graduated high school 1627 (56.6)
Some College/Graduated college 899 (31.3)
Other 16 (0.6)
Insurance* Public 2223 (70.5)
Private 930 (29.5)
*Insurance type was designated as public if Medicare, Medicaid, or Mass health and private for
all others.
WC = waist circumference; SBP = systolic blood pressure; DBP = diastolic blood pressure, MetS
= metabolic syndrome; TSH = thyroid stimulating hormone; HgbA1c = hemoglobin A1C; HDL-
C = high density lipoprotein cholesterol; BMI = body mass index
Table 2: Demographic characteristics of subjects with and without MetS (n=1005)
MetS (-) n (%) MetS (+) n (%) P value
Gender Female 253 (89.4) 527 (73.0) <0.0001
Race White 56 (20.7) 147 (20.8) 0.0198
African American 72 (26.6) 258 (36.5)
Hispanic 101 (37.3) 213 (30.1)
Asian 1 (0.4) 10 (1.4)
Middle eastern 4 (1.5) 6 (0.9)
Other 37 (13.6) 73 (10.3)
Highest
education
level
8t
h
grade or less 16 (7.04) 64 (10.5) 0.347
Some/graduated HS 123 (54.2) 363(59.3)
Some/graduated
College
87 (38.3) 183 (29.9)
Other 1(0.44) 2(0.33)
Insurance Public 154(63.4) 475(72.7) 0.006
Smoking
status
Never 144 (78.3) 347 (64.9) 0.002
Median Age (Range) (yrs.) 34 (18-65) 45 (18-93) <0.0001
Median WC (Range) (inches) 44 (31.5-60) 49 (36-83) <0.0001
WC = waist circumference; SBP = systolic blood pressure; DBP = diastolic blood pressure, MetS
= metabolic syndrome; TSH = thyroid stimulating hormone; HgbA1c = hemoglobin A1C; HDL-
C = high density lipoprotein cholesterol; BMI = body mass index
Median SBP (Range) (mm Hg) 115 (89-135) 133 (89-244) <0.0001
Median DBP (Range) (mm Hg) 75 (58-92) 81 (52-134) <0.0001
Median TSH (Range) (µIU/ML) 1.36 (0.34-10.07) 1.41(0.01-60.32 0.45
Median HgbA1c (Range) (%) 5.4 (3.9-14.5) 6.3 (4.7-15.10) <0.0001
Median HDL-C (Range) (mg/dL) 50 (24-114) 39.5 (16-95) <0.0001
Median BMI (Range) (kg/m2) 37 (25-64) 40 (25-85) <0.0001
TSH = thyroid stimulating hormone
Table 3: Multivariate analyses to determine associations between TSH and metabolic syndrome.
ȕ coefficient Standard error P value
TSH 0.0933 0.1227 0.4471
Age 0.0588 0.00925 <.0001
Gender -1.0990 0.3354 0.0010
Race 0.0331 0.0756 0.6611
Education level -0.0479 0.0895 0.5926
Insurance type 0.0522 0.2423 0.8295
Smoking status 0.1090 0.1469 0.4582
... The liver [8][9][10], adipose tissue [8], skeletal muscle [11], and pancreas [12] are under the influence of thyroid hormone action. Many studies have elucidated the relationship between thyroid hormones and glucose homeostasis [10,[13][14][15]. It is generally accepted that thyroid hormones have significant effects on glucose homeostasis and insulin resistance [9]. ...
... However, data on how glucose homeostasis changes in response to subtle thyroid hormone alterations are not yet consistent. Several studies have assessed the association between thyroid dysfunction and glucose homeostasis, but the data are conflicting [14,15,17]. Recently, Kim et al. [18] reported that HbA1c levels were high in non-diabetic patients with overt hypothyroidism, but only 45 patients were analysed. ...
Article
Full-text available
Background/aims: Thyroid hormones are involved in wide range of glucose metabolism functions. Overt thyroid dysfunctions are related to altered glucose homeostasis. However, it is not conclusive as to whether subtle changes in thyroid hormones within normal ranges can induce alterations in glucose homeostasis. The aim of this study was to evaluate the association between thyroid hormone and glucose homeostasis parameters in subjects without overt thyroid dysfunction based on nationwide population data. Methods: In the Sixth Korea National Health and Nutrition Examination Survey 2015 (n = 7,380), data were collected from subjects with insulin and thyroid function measurements who were older than 19-years-old. After the exclusion of 5,837 subjects, a total of 1,543 patients were included in the analysis. Subjects were categorized into the quartiles of the free thyroxine (FT4). Fasting glucose, insulin, homeostatic model assessment of insulin resistance and hemoglobin A1c (HbA1c) levels were considered to be glucose homeostasis parameters. Results: Subjects with the highest FT4 quartile showed significantly lower fasting insulin and HbA1c levels. A significant inverse correlation FT4 and HbA1c levels was observed (β = -0.261, p = 0.025). In the logistic regression analysis, the highest quartile of FT4 was demonstrated to lower the risk of HbA1c to a greater degree than the median by approximately 40%, after adjusting for confounders, compared to the lowest quartile (p = 0.028). Conclusions: We demonstrated subjects with a lower FT4 quartile exhibited high risk of HbA1c levels above the median value in a representative Korean population. Subjects with the lowest FT4 quartile should be cautiously managed in terms of altered glucose homeostasis.
... In a study by Kommareddy et al. in adults, there has been no evidence of a link between serum TSH levels and the existence of MetS with obesity. 40 By contrast, TSH levels may affect the occurrence of MetS, but not all of the MetS criteria, according to a study by Özer et al. which included 260 obese children and adolescents. 13 In our research, there was no difference in the presence of MetS between the groups with and without IH. ...
Article
Full-text available
Objective: The aim of this study is to look at the relationship between hyperthyrotropinemia and anthropometric measurements as well as cardiometabolic risk factors in obese children and adolescents. Materials and methods: A total of 100 patients with isolated hyperthyrotropinemia and 124 patients with normal thyroid functions, between 10 and 18 years of age, were included in the study. Anthropometric and blood pressure measurements and biochemical parameters were recorded. Non-high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol, and triglyceride/high-density lipoprotein cholesterol ratios were calculated. Results: The subjects' mean age was 12.6 ± 1.9 years and their mean body mass index was 29.8 ± 4 kg/m2. The isolated hyperthyrotropinemia group had considerably greater levels of triglyceride, non-high-density lipoprotein cholesterol, and the triglyceride/high-density lipoprotein cholesterol ratio. Higher prevalences of hypertriglyceridemia and increased triglyceride/high-density lipoprotein cholesterol ratio were found in the group with isolated hyperthyrotropinemia. Thyroid-stimulating hormone had a statistically significant positive relationship with triglyceride, non-high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride/high-density lipoprotein cholesterol ratio, as well as an inverse relationship with high-density lipoprotein cholesterol. Thyroid-stimulating hormone was positively correlated with triglyceride and triglyceride/high-density lipoprotein cholesterol ratio in both females and males; however, only in females, thyroid-stimulating hormone was positively correlated with non-high-density lipoprotein cholesterol and total cholesterol/highdensity lipoprotein cholesterol ratio. The triglyceride/high-density lipoprotein cholesterol ratio, as well as the rates of hypertriglyceridemia were higher in children with isolated hyperthyrotropinemia in the female subgroup. Male children with isolated hyperthyrotropinemia had significantly higher triglyceride levels in comparison with males with normal thyroid-stimulating hormone. Conclusion: The present study suggested that isolated hyperthyrotropinemia is associated with the deterioration of lipid metabolism, especially in females. Since dyslipidemia is accepted as a cardiovascular disease risk factor, isolated hyperthyrotropinemia might negatively influence cardiovascular functions in obese children and adolescents.
... Also, reduction in level of FT4 is associated with visceral obesity and increased insulin resistance. In addition to, high risk of MetS was found in patients with elevated TSH levels [14][15][16]. ...
Article
Full-text available
Background Metabolic syndrome (MetS) and thyroid dysfunction have a degree of close association, and each of them affects the other. Due to the associated cardiovascular events, MetS has increased morbidity and mortality. The study tried to detect the frequency of thyroid function in patients with MetS. This is a case control study that recruited 100 patients with MetS and 100 healthy control subjects. Results Patients with MetS had significantly higher body mass index and waist circumference. Also, frequency of thyroid dysfunction was significantly higher in MetS group (32% vs. 9%; P <0.001). The most frequent form of thyroid dysfunction was subclinical hypothyroidism: 21% of the MetS group and 6% of the control group. Out of the studied patients with MetS, 13 (13%) patients had three criteria, 55 (55%) patients had four criteria, and 32 (32%) patients had five criteria for MetS. Conclusion Patients with MetS are vulnerable to develop thyroid dysfunction mainly subclinical hypothyroidism. So, it is recommended to perform regular screening for those patients as regard thyroid dysfunction.
... In obese and overweight African Americans, there is no significant association between serum TSH levels and MS. After correcting for age, gender, ethnicity, educational background, socioeconomic status, and smoking, no significant associations between TSH and the components of MS were found [11]. is negative result is consistent with that found in euthyroid Taiwanese individuals [12]. e controversial results probably are attributed to the slightly different definition of MS, adjusted confounders, and ethnicity-and disease-based population. ...
Article
Full-text available
Background: Metabolic syndrome (MS) and its components have been demonstrated to facilitate the prevalence of thyroid nodules (TNs). The underlying pathogenesis needs to be elucidated. Methods: A total of 2722 subjects, who underwent health checkup in our institute from December 2014 to November 2018, were retrospectively and randomly collected. After exclusion, 2068 subjects were chosen, and their anthropic and clinical data were collected. Results: After matching age, gender, uric acid (UA), and creatinine (Cr) by propensity score matching (PSM), subjects with MS had higher prevalence of TNs than those without MS, as well as higher thyroid-stimulating hormone (TSH) and inflammatory levels, indicated by the higher white blood cell (WBC), lymphocyte (LY), and monocyte/high-density lipoprotein (Mo/HDL). After matching age, gender, UA, Cr, TSH, free triiodothyronine (FT3), thyroxine (FT4), WBC, NE, LY, Mo, NE/LY, LY/Mo, and Mo/HDL by PSM, no significant difference of the prevalence of TNs was found between MS and non-MS groups. Step logistic regression suggested glucose intolerance (GI), among all the components of MS, was an independent impact factor of TNs and was considered to contribute most to the formation of TNs. The prevalence of TNs was higher in the GI group after matching age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood sugar (FBS), UA, Cr, triglyceride (TG), cholesterol (CHOL), HDL, and low-density lipoprotein (LDL). Conclusions: Patients with MS have a higher prevalence of TNs, probably due to the elevated TSH and inflammatory levels in vivo. Among the components of MS, glucose intolerance contributes most to the development of TNs.
... Other studies suggested an increased risk of MS in patients with elevated TSH levels [39,40], whereas FT4 levels have been shown to be associated with four of the five components of the MS [15]. More recently, no significant associations between serum TSH levels and prevalence of MS or individual components of the MS in obese and overweight individual have been reported [41]. However, no serum FT4 levels were available in this study and no associations between FT4 and individual component of the MT could be done. ...
Article
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Metabolic syndrome (MS) increases cardiovascular risk. The role of thyroid hormone on components of MS is unclear. We analyzed a sample of 4733 euthyroid subjects from SardiNIA study. In female thyrotropin (TSH) was significantly and positively associated with triglycerides (Standardized regression coefficients (β) = 0.081, p < 0.001). Free thyroxine (FT4) was positively associated with HDL (β = 0.056, p < 0.01), systolic blood pressure (SBP) (β = 0.059, p < 0.001), diastolic blood pressure (DBP) (β = 0.044, p < 0.01), and fasting glucose (β = 0.046, p < 0.01). Conversely, FT4 showed a negative association with waist circumference (β = −0.052, p < 0.001). In TSH was positively associated with triglycerides (β = 0.111, p = <0.001) and FT4 showed a positive association with DBP (β = 0.51, p < 0.01). The addition of leptin and adiponectin to the regression models did not substantially change the impact of thyroid hormones on components of MS. Our data suggest that, even within the euthyroid range, excess of truncal adipose tissue is associated with variations in FT4. Leptin and adiponectin exert an additive effect rather than a causal effect. Additional studies should be performed to determine the clinical significance of this finding.
... We suggest that other metabolic parameters may be included in studies designed to relieve thyroid function status in obese patients. Kommareddy et al. reported the study to assess an association between TSH level and metabolic syndrome in obese and overweight patients (16). In that study, no statistically significant association were determined between the TSH levels and the metabolic syndrome. ...
... TSH with higher total cholesterol 24 , higher low-density lipoprotein (LDL)-cholesterol 24 , lower high-density lipoprotein (HDL)-cholesterol 25 , and higher HbA 1c 25 , and of higher FT4 with lower LDL-cholesterol 26 , higher HDL-cholesterol 27 , and lower fasting glucose 26 . However, some studies have found no association [27][28][29][30][31] . Observationally, people who are TPOAb-positive have higher TSH and faster carotid intima media thickness (cIMT) progression 32 , however, in another study, cardiovascular risk associated with subclinical hypothyroidism did not differ by TPOAb status 33 . ...
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To clarify the role of thyroid function in ischemic heart disease (IHD) we assessed IHD risk and risk factors according to genetically predicted thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase antibody (TPOAb) positivity. Separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) was used in an extensively genotyped case (n = 64,374)-control (n = 130,681) study, CARDIoGRAMplusC4D. Associations with lipids, diabetes and adiposity were assessed using the Global Lipids Genetics Consortium Results (n = 196,475), the DIAbetes Genetics Replication And Meta-analysis case (n = 34,380)-control (n = 114,981) study, and the Genetic Investigation of ANthropometric Traits (body mass index in 152,893 men and 171,977 women, waist-hip ratio in 93,480 men and 116,741 women). Genetically predicted thyroid function was not associated with IHD (odds ratio (OR) per standard deviation for TSH 1.05, 95% confidence interval (CI) 0.97 to 1.12; for FT4 1.01, 95% CI 0.91 to 1.12; for TPOAb positivity 1.10, 95% CI 0.83 to 1.46) or after Bonferroni correction with risk factors, except for an inverse association of FT4 with low-density lipoprotein-cholesterol. The associations were generally robust to sensitivity analyses using a weighted median method and MR Egger. This novel study provides little indication that TSH, FT4 or TPOAb positivity affects IHD, despite potential effects on its risk factors.
... Hence more studies have to be done with regard to glycemic control mediated effects on hypothyroid pituitary axis in patients with T2DM. A study undertaken by Koonareddy et al. assessed thyroid function in metabolic syndrome in obese and overweight patients [43]. According to the study, serum TSH level does not appear to be a modifiable risk factor in obese and overweight subjects with metabolic syndrome. ...
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Aim: The study was primarily aimed at investigating the association of Magnesium and Zinc levels in the serum of adult Non- obese and Obese type 2 diabetic patients, with particular reference to thyroid comorbidity. Methods: 108 patients with T2DM of both genders (24 Non obese and 84 Obese) were enrolled from a tertiary health care unit in Puducherry. The cardio-metabolic risk factors were assessed through body mass index, Waist hip ratio, blood pressure, fasting blood glucose, lipid profile and glycated haemoglobin. Zinc and Magnesium were quantitated. Insulin resistance was by Homeostasis model assessment. Serum free T4, T3 and TSH were also measured. Results: In non-obese type 2 diabetic group, Glycated haemoglobin had a strong positive correlation with free T4(r=0.784; p=0.003).TSH also depicted a positive association with HOMA-IR (r=0.924; p<0.001); whereas,T3 and Insulin had negative correlation with Magnesium (r=-0.599* and r=-0.620*; p 0.04 and 0.031). The levels of Zinc and Magnesium in the serum of obese diabetic patients had a positive correlation among them (r=0.565#; p<0.001). TAG/HDL ratio a measure of small dense LDL is positively correlated with LDL in both groups (r=0.881 and 0.912) with p value<0.001 for both. Conclusion: Correlation among Glycemic control, Insulin resistance, Thyroid hormones, divalent cations and dyslipidemia depict differential characteristics in obese and non-obese type2 diabetes with Thyroid comorbidity.
... Data about this issue, however, are still conflicting. No significant association between serum TSH levels and the presence of MetS has been reported in obese and overweight adults [24]. By contrast, other authors have shown in a group of 260 obese children and adolescents that TSH levels may affect the occurrence of MetS, but not all of the MetS parameters [25]. ...
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Purpose: Mild TSH elevations are frequently observed in obese patients, in the absence of any detectable thyroid disease. Our objective is to evaluate the relationship between the raised TSH levels and the biochemical and clinical consequences of obesity. Methods: This is a retrospective cross-sectional study of a large population of obese children and adolescents. We evaluated 833 subjects (340 m, 493 f), aged 14.4 ± 2.5 (range 5.2-18.5) years, height SDS 0.27 ± 1.04 (-3.49-4.35), and BMI SDS 2.94 ± 0.59 (1.60-4.68). Body composition, free T4, TSH, anti-TPO antibodies, anti-TG antibodies, inflammation markers (total WBC and the subtypes, ultrasensitive C-reactive protein), and metabolic parameters [AST, ALT, γGT, ALP, glycaemia, insulin, total cholesterol (TC), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C), triglycerides (TG)] were measured, and oral disposition index (ODI) and cardiovascular risk factors (TC/HDL-C and TG/HDL-C) were calculated. After exclusion of the subjects showing anti-thyroid antibodies, the remaining 779 (325 m, 454 f) were then subdivided into two subgroups according to a TSH value below (group A) or above (group B) 4.5 mU/L. Results: Clinical characteristics and hematological markers of patients with and without positive anti-thyroid antibodies were similar, with the exception of higher TSH levels in the latter group. Using analysis of covariance, the subjects of group B had significantly higher values of TC (170.3 ± 28.7 vs 163.3 ± 32.9 mg/dL; p < 0.05), systolic (125.8 ± 13.5 vs 124.5 ± 13.1 mm/Hg), and diastolic blood pressure (79.2 ± 8.0 vs 77.9 ± 8.2 mm/Hg) than subjects of group A. No difference was observed in body composition, ODI, and the cardiovascular risk factors between these two groups. Conclusion: TSH elevation in overweight and obese children and adolescents, being associated with a higher TC and blood pressure, might negatively influence the cardiac status. Longitudinal studies are requested, however, to confirm this hypothesis and, therefore, to conclude whether a substitutive treatment with l-thyroxine is really needed in these patients.
Purpose of review: To summarize recent developments in the association of thyroid function with metabolic syndrome (MetS). Recent findings: Although thyroid hormones even within low normal range are associated with various metabolic abnormalities, the risk of MetS remains a controversial issue. Hyperthyroid state might be associated only with insulin resistance and dysglycemia. Autoimmune thyroid diseases may be a potential risk factor for metabolic abnormalities even in those with low normal thyroid function. Summary: The interrelation between thyroid stimulating hormone, free T3, freeT4 and metabolic parameters is complex and might be affected by age, sex, BMI, insulin resistance, smoking, iodine intake and inflammatory markers.
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It is currently unclear whether subclinical thyroid dysfunction is associated with blood pressure. Furthermore, data on the potential relation of thyroid function with blood pressure in children and adolescents are sparse. We investigated the association between serum TSH levels and blood pressure in a population-based study conducted in children aged 3-10 yr and adolescents aged 11-17 yr. Data from 6435 children and 5918 adolescents of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were analyzed. Two readings of systolic and diastolic blood pressure were taken in a sitting position after 5 min of rest. Hypertension was defined by an increased systolic or an increased diastolic blood pressure using age-, sex-, and height-specific reference values from the KiGGS study. Serum TSH levels were measured with the electrochemiluminescence method. High and low serum TSH levels were defined according to age-specific reference limits for the assay. Continuous and categorized serum TSH levels were associated with hypertension by multivariable logistic regression. Serum TSH levels were significantly associated with hypertension in children (odds ratio=1.12; 95% confidence interval=1.00-1.25; P=0.045) and adolescents (odds ratio=1.19; 95% confidence interval=1.12-1.26; P<0.001). High serum TSH levels were positively associated with systolic and diastolic blood pressure, but not with hypertension in children and adolescents. There is a positive relationship between serum TSH levels and hypertension in children and adolescents, suggesting that subclinical hypothyroidism is associated with an increased risk of hypertension.
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In Reply We agree with Dr Rotondi and colleagues and Dr Takamura and colleagues that the mediating factors between subclinical hypothyroidism and CHD remain to be determined, since in our study the associations between subclinical hypothyroidism and CHD remained of similar magnitude after adjustment for traditional cardiovascular risk factors. Rotondi et al hypothesized that inclusion of obese individuals might explain the lack of the significant association with CHD among adults with minimal TSH elevations. We disagree with this hypothesis for several reasons.
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Objective Thyroid dysfunction may accelerate atherosclerosis. Aortic pulse wave velocity (PWV) is an early index of arterial stiffness and an important risk factor for cardiovascular disease and might therefore be linked to changes in thyroid activity. We investigated the relationship between thyroid function and carotid-femoral PWV, as an index of arterial stiffness.DesignCross-sectional cohort study.PatientsParticipants from the SardiNIA study. Those being treated for thyroid diseases were excluded, yielding a sample of 5875 aged 14-102.MeasurementsClinical parameters, blood tests including serum TSH and serum FT4, and carotid-femoral PWV were measured.ResultsAfter adjusting for confounders, a direct and linear association between FT4 and PWV was shown (multiple regression analysis). The model containing age, mean blood pressure, body mass index, heart rate, FT4, hypertension, diabetes and dyslipidaemia accounted for 55% of the variation in PWV.Conclusions Like several other known risk factors, serum FT4 levels are associated with carotid-femoral PWV, suggesting that high FT4 levels have a detrimental effect on aortic stiffness and may contribute to ageing process of the vascular system. This finding may help to understand the pathogenesis of cardiovascular disease and contribute to improve prevention therapy.
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To review several of the most recent and most important clinical studies regarding the effects of thyroid treatments on weight change, associations between thyroid status and weight, and the effects of obesity and weight change on thyroid function. Weight decreases following treatment for hypothyroidism. However, following levothyroxine treatment for overt hypothyroidism, weight loss appears to be modest and mediated primarily by loss of water weight rather than fat. There is conflicting evidence about the effects of thyroidectomy on weight. In large population studies, even among euthyroid individuals, serum thyroid-stimulating hormone is typically positively associated with body weight and BMI. Both serum thyroid-stimulating hormone and T3 are typically increased in obese compared with lean individuals, an effect likely mediated, at least in part, by leptin. Finally, there is no consistent evidence that thyroid hormone treatment induces weight loss in obese euthyroid individuals, but thyroid hormone analogues may eventually be useful for weight loss. The interrelationships between body weight and thyroid status are complex.
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LR: 20061115; JID: 7501160; 0 (Antilipemic Agents); 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 57-88-5 (Cholesterol); CIN: JAMA. 2001 Nov 21;286(19):2401; author reply 2401-2. PMID: 11712930; CIN: JAMA. 2001 Nov 21;286(19):2400-1; author reply 2401-2. PMID: 11712929; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712928; CIN: JAMA. 2001 Nov 21;286(19):2400; author reply 2401-2. PMID: 11712927; CIN: JAMA. 2001 May 16;285(19):2508-9. PMID: 11368705; CIN: JAMA. 2003 Apr 16;289(15):1928; author reply 1929. PMID: 12697793; CIN: JAMA. 2001 Aug 1;286(5):533-5. PMID: 11476650; CIN: JAMA. 2001 Nov 21;286(19):2401-2. PMID: 11712931; ppublish