Endocrine Care
Thyroid Function and Metabolic Syndrome: A Population-Based
Thyroid Study
Authors
Ladan Mehran1, Atieh Amouzegar1, Parnian Kheirkhah Rahimabad1,
Maryam Tohidi2, Zhale Tahmasebinejad1, Fereidoun Azizi1
Affiliations
1 Endocrine Research Center, Research Institute for Endocrine
Sciences, Shahid Beheshti University of Medical Sciences, Tehran,
I. R. Iran
2 Prevention of Metabolic Disorders Research Center, Research
Institute for Endocrine Sciences, Shahid Beheshti University of
Medical Sciences, Tehran, I. R. Iran
Key words
metabolic syndrome, thyroid, hypothyroidism, hyperthyroidism
Bibliography
DOI http://dx.doi.org/10.1055/s-0042-117279
Horm Metab Res 2017; 49: 192–200
© Georg Thieme Verlag KG Stuttgart · New York
ISSN 0018-5043
Correspondence
F. Azizi
Professor of Internal Medicine and Endocrinology
Endocrine Research Center
Research Institute for Endocrine Sciences
Shahid Beheshti University of Medical Sciences
P.O. Box: 19395 4763
Tehran
I. R. Iran
Tel.: + 98/21/22432 503, Fax: + 98/21/22402 463
azizi@endocrine.ac.ir
Introduction
Thyroid hormones affect lipid and glucose metabolism, blood pres-
sure, and body weight, all of which are associated with various met-
abolic parameters; abnormal thyroid function may hence result in
the development of metabolic syndrome (MetS) [1]. MetS is a clus-
ter of risk factors including abdominal obesity, hypertension, dys-
lipidemia, and impaired fasting glucose [2]. The exact pathogene-
sis of MetS is yet unknown, but has been closely linked to insulin
resistance and obesity [2, 3], which are both affected by thyroid
hormones, increase or decrease in thyroid hormones alter glucose
metabolism and leads to insulin resistance [4, 5].
Overt hypothyroidism is a known cardiovascular risk factor;
however, there is no consensus regarding the impact of subclinical
hypothyroidism (SCH) on MetS and its components [6]. Although
many studies have investigated the relationship between thyroid
dysfunction and components of MetS, their reports are conflicting
and hampered by insufficient statistical power, and not assessing
MetS as a whole entity even in overt hypothyroid subjects.
192
Supporting Information for this article is available online at
http://www.thieme-connect.de/products.
Abs tr ac t
The impact of thyroid dysfunction in subclinical ranges on metabolic
syndrome (MetS) is not well known. The aim of the present study is to
evaluate the association of thyroid dysfunction with MetS and its com-
ponents. In the cross-sectional population-based Tehran Thyroid Study,
out of 5 786 randomly selected participants, aged ≥ 20 years, subjects
with thyroid nodules and cancer or any severe systemic disease, those
who were pregnant and those using thyroid medication were excluded,
leaving 5 422 subjects to be investigated. Body weight, waist circum-
ference, and blood pressure were measured. Fasting blood glucose and
Downloaded by: Boston University. Copyrighted material.
concentrations of lipids and lipoproteins, free T4, and TSH were assayed.
Mean age of the participants was 40.3 ± 14.4 of whom 101 (2 %) had
overt hypothyroidism, 294 (5 %) subclinical hypothyroidism, 82 (2 %)
overt hyperthyroidism, and 178 (3 %) had subclinical hyperthyroidism;
1 704 (32 %) had MetS. Clinically hypothyroid subjects had the highest
prevalence of MetS (41.6 %), abdominal obesity (45 %), and hypertri-
glyceridemia (58 %) compared to other groups (p < 0.05). Significant
odds ratio for prevalent MetS was observed only in clinically hypothyroid
men [OR: 2.9, 95 % CI: 1.04, 8.4, p = 0.04]. In women, the association
between overt hypothyroidism and MetS was marginally significant only
in the crude model [OR: 0.068, 95 % CI (0.97–2.42), p = 0.06]. There was
higher risk of Mets in subclinically hypothyroid subjects, aged > 50.
Overt and subclinical hyperthyroidism had significantly higher odds of
hyperglycemia in men and women after full adjustment for age, smok-
ing, and BMI. Overt hypothyroidism and subclinical hypothyroidism
especially in the elderly could be associated with MetS. Hyperthyroidism
may induce hyperglycemia.
Metabolic syndrome and thyroid dysfunction are very common
endocrine disorders with many common features regarding their
metabolic aspects [7], morbidity and mortality [8, 9]. The features
of MetS may be increased in hypothyroid or subclinical hypothy-
roid states; their coexistence may have great impact on the indi-
vidual’s health regarding cardiovascular and metabolic risk factors
especially in the elderly. It is unclear whether thyroid dysfunction
in different ranges is associated with MetS; therefore, the current
study evaluated the association of thyroid dysfunction with MetS
and its components in a large number of individuals in a popula-
tion based study in Tehran, the capital of Iran.
Materials and Methods
Study design
This is a cross-sectional study conducted within the framework of
the Tehran Thyroid Study (TTS) [10], a cohort study, being conduct-
ed within the framework of Tehran Lipid and Glucose Study (TLGS)
Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
which is a long term integrated community-based study for
­i dentification and prevention of non-communicable disorders
(NCD) initiated in 1997 with follow-ups at 3 year intervals [11]. This
population-based survey was carried out in an iodine sufficient
area [12].
Study population
Between March 1997 and December 2004, 5 786 individuals,
aged ≥ 20 years, residents of district 13 of Tehran, were selected
using multistage cluster random sampling. District No. 13, with an
area of about 13 sq km is located in the eastern part of urban Teh-
ran. Three medical health centers in this area which have the field
data of > 90 % of all covered families, were selected. The population
of this area is representative of the overall population of Tehran
(Iran National Census, 1996) [11]. Baseline measurements were
documented and participants were invited for follow-up studies
every 3 years.
We excluded those with thyroid cancer (22), thyroid nodules
(299), thyroid surgery (70), pregnant women (50), those taking
anti-thyroid drugs (19), levothyroxine (143), steroid hormones,
lithium, amiodarone, and anticonvulsants (94), and participants
with incomplete laboratory or missing data (14). Finally, 5 422 sub-
jects aged ≥ 20 years remained for the study analysis.
Medical history and clinical examination
At the first visit, the study was explained to subjects and demo-
graphic data were obtained. All clinical examinations were per-
formed by trained physicians at the beginning of the study and
again every 3 years for all subjects who were invited to the TTS unit
and after providing informed written consent, were referred to
trained physicians. Participants were interviewed to obtain past
medical history, detailed personal and family history regarding pos-
sible thyroid diseases such as goiter, hyperthyroidism, or hypothy-
roidism and current medication; information on radioiodine intake,
smoking habits, physical activity levels, and any medication that
could interfere with thyroid function test results was also obtained.
Participants remained seated for 15 min, when a qualified phy-
sician measured blood pressure twice with a standard mercury
sphygmomanometer, calibrated by the Iranian Institute of Stand-
ards and Industrial Researches. Blood pressure was measured on
the right arm, at the heart level. Blood pressure was measured twice
and the mean was considered as the patient’s BP. Anthropometric
measurements were taken with shoes removed and the partici-
pants wearing light clothing. Weight and height were measured
according to standard protocols. Waist circumference (WC) was
measured at the level of the umbilicus and hip circumference was
measured at the widest girth of the hip in centimeters. Body mass
index (BMI) was calculated by dividing the weight in kilograms by
the square of height in meters.
The ethical committee of the Research Institute for Endocrine
Sciences of Shahid Beheshti University of Medical Sciences ap-
proved the protocol for this study.
Laboratory measurements
Fasting blood samples were drawn from all participants between
7:00–9:00 AM. The 75 g oral glucose tolerance test (OGTT) was also
done in participants who were not taking glucose lowering drugs.
Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
Fasting and 2-h glucose concentrations were assayed, using the en-
zymatic colorimetric method with the glucose oxidase technique.
Serum total cholesterol (TC) and triglycerides (TGs) were measured,
using the enzymatic calorimetric method with cholesterol ester-
ase and cholesterol oxidase and glycerol phosphate oxidase, re-
spectively. High density lipoprotein-cholesterol (HDL-C) was meas-
ured after precipitation of the apolipoprotein B containing lipopro-
teins with phosphotungistic acid. Low density
lipoprotein-cholesterol (LDL-C) was calculated from serum TC, TGs,
and HDL-C concentrations expressed in mg/dl using the Friedwald
formula, if TG concentration was < 400 mg/dl. All biochemical tests
were performed on the day of sampling, using commercial kits
(Pars Azmoon Inc., Tehran, Iran) by the Selectra 2 auto-analyzer
(Vital Scientific, Spankeren, The Netherlands). All samples were
analyzed when quality control met the acceptable criteria. Both
inter- and intra-assay coefficients of variation were less than 2.3 %
for glucose, < 2.1 % for TG, < 2 % for TC, and < 3 % for HDL- C.
FT4 and TSH were determined in serum samples (stored at
–70 °C) by the electrochemiluminescence immunoassay (ECLIA)
method, using Roche Diagnostics kits & Roche/Hitachi Cobas e-411
Downloaded by: Boston University. Copyrighted material.
analyzer (GmbH, Mannheim, Germany). The intra- and interassay
CVs were 1.3 and 3.7 % for FT4 and 1.5 and 4.5 % for TSH determi-
nations, respectively. Thyroid peroxidase antibody (TPO Ab) was
assayed by the immunoenzymometric assay (IEMA), using the re-
lated kit (Monobind, Costa Mesa, CA, USA) and the Sunrise ELISA
reader (Tecan Co., Salzburg, Austria); intra- and interassay CVs were
3.9 and 4.7 %, respectively.
Definitions
Euthyroidism was defined as TSH reference range of 0.32–
5.06 mIU/l (0.32 ≤ TSH ≤ 5.06 while not taking any thyroid medica-
tion or agent interfering with thyroid function test results. Other
thyroid test results such as (TSH > 5.06 and 0.91 ≤ FT4 ≤ 1.55),
(TSH > 5.06 and FT4 < 0.91), (TSH < 0.32 and 0.91 ≤ FT4 ≤ 1.55) and
(TSH < 0.32 and FT4 > 1.55) were considered as subclinical hypo-
thyroidism, overt hypothyroidism, subclinical hyperthyroidism and
overt hyperthyroidism, respectively. TSH and FT4 reference rang-
es were defined based on normal reference range of the present
population [13].
In this study, we considered MetS criteria according to the Joint
Interim Statement (JIS) [14], which is defined as the presence of at
least 3 of the following: 1) waist Circumference > 95 cm in both
genders for Iranian population [15]; 2) serum TGs ≥ 150 mg/dl or
on specific treatment; 3) HDL-C < 40 mg/dl in males and < 50 mg/
dl in females or on specific treatment; 4) systolic blood pressure
(SBP) ≥ 130 mmHg or diastolic blood pressure (DBP) ≥ 85 mmHg or
on specific treatment for previously diagnosed hypertension, and
5) fasting blood sugar (FBS) ≥ 100 mg/dl or on treatment for diabe-
tes. Based on the results of the large cohort Tehran Lipid Glucose
Study, anthropometric cut-offs, based on European populations
are not appropriate for Iranians and WC cut-off points, based on
both cross-sectional and longitudinal outcome based studies, are
equal in both genders.
Statistical analysis
All statistical analyses were performed with SPSS 16.0 software and
p-values < 0.05 were considered statistically significant. Demo-
193
 Endocrine Care

▶Table 1 Baseline characteristics of the study population by thyroid function group.

Euthyroid Overt hypothy- Subclinical Overt hyperthy- Subclinical hyperthy-

(n = 4 748) roid (n = 101) hypothyroid roid (n = 82) roid (N = 178)
(n = 294)

Age (years) 40.1 ± 14.4 44.7 ± 13.4† 39.2 ± 14.9 41.0 ± 14.1 44.2 ± 13.8†

Gender ( %)
Male 44.6 16.8† 23.8† 42.7 40.4
Female 55.4 83.2 76.2 57.3 59.6
Smoking ( %) 12.0 6.9 5.4† 14.6 10.7
Weight (kg) 70.4 ± 12 73.5 ± 13 * 67.8 ± 13† 69.0 ± 12 70.0 ± 11
WC (cm) 87.5 ± 12 92.8 ± 11† 86.1 ± 13 87.8 ± 11 88.3 ± 11.6
BMI (kg/m²) 26.5 ± 4.6 29.1 ± 4.7† 26.5 ± 4.7 26.1 ± 4.1 26.5 ± 3.8
TC (mg/dl) 200 ± 45 218 ± 45† 200 ± 48 171 ± 35† 200 ± 43
HDL-C (mg/dl) 41.4 ± 10 41.8 ± 11 42.5 ± 11 39.1 ± 11 * 41.7 ± 10
LDL-C (mg/dl) 128 ± 36 140 ± 36 * 128 ± 39 105 ± 28† 125 ± 36
TG (mg/dl) 135 (91–197) 158 (102–253) * 125 (86–208) 125 (87–183) 143(101–204)

Downloaded by: Boston University. Copyrighted material.

FBS (mg/dl) 95 ± 28 93 ± 20 98 ± 37 97 ± 26 102 ± 34 *
2-hPG (mg/dl) 112.0 ± 49.4 122.3 ± 57.2 * 117.4 ± 65.5 118.8 ± 47.0 120.6 ± 62.6
Fasting serum insulin (mIU/l) 7.6 (5.4–10.6) 8.6 (5.6–11.9) 8.4 (6.1–11.7) * 9.5 (5.3–11.9) 7.9(5.5–10.7)
HOMA-IR 1.7 (1.2–2.5) 1.9 (1.3–2.9) 1.9 (1.3–2.9) * 2.2 (1.2–2.8) * 1.9(1.4–2.6) *
Systolic BP (mmHg) 117 ± 17 117 ± 18 117 ± 18 119 ± 16 117 ± 17
Diastolic BP (mmHg) 76 ± 10 77 ± 9 75 ± 10 75 ± 9 76 ± 11
TSH (mIU/l) 1.6 (1.0–2.4) 13.3 (7.7–37.4)† 6.6 (5.6–8.4)† 0.02 (0.01–0.06)† 0.19(0.07–0.25)†
FT4 (ng/dl) 1.2 ± 0.2 0.7 ± 0.2† 1.1 ± 0.1† 2.5 ± 2.6† 1.3 ± 0.1†

Values are presented as mean ± SD except for TG, HOMA-IR, TSH, and Insulin, which are presented as median (IQR); p-Values are for comparision with
euthyroid subjects; * p < 0.05; † p < 0.001

graphic, clinical and laboratory data of subjects by thyroid function Results

groups are presented as mean ± SD for normal distribution varia-
bles and median, interquartile range (IQR) for skewed variables.
Data between different groups of thyroid function were compared,
using ANOVA and Kruskal Wallis based on variables’ distribution.
The correlation of serum TSH with FT4 values with metabolic vari-
ables was calculated using Pearson and Spearman correlation for
normal and abnormal distribution variables, respectively. Linear
regression analyses were performed with lipid parameters, WC,
SBP, DBP, FBS, and insulin at different levels of adjustment. The
quality of model was derived from R2 value. The impact of signifi-
cantly associated variables on the dependent variables was evalu-
ated using the unstandardized β coefficient.
The prevalence of MetS and its components among different
groups of thyroid function was compared using the Chi-square test.
Logistic multivariate analysis was used to calculate odds of preva-
lent MetS and its components adjusted for age, sex, and smoking.
Logistic multivariate analysis (age and sex adjusted) was used to
evaluate the association between FT4 and TSH with MetS. Odds ratio
for MetS was reported, based on FT4 as continuous and categorized
variables. Odds ratio for MetS was calculated based on the 2 waist
circumferences cut off points of 90 and 95 cm for definition of MetS.
Mean age of the study population (n = 5 422) was 40.3 ± 14.4 years,
of these 2 318 (42.8 %) were males and 3 104 (57.2 %) were females;
4 748 (88 %) of the participants were euthyroid, 101 (2 %) clinically
hypothyroid, 294 (5 %) subclinically hypothyroid, 82 (2 %) clinically
hyperthyroid and 178 (3 %) had subclinical hyperthyroidism; 1 704
participants (32 %) had metabolic syndrome. Baseline characteris-
tics of the study population are shown in ▶Table 1. There were sig-
nificant differences in age, weight, waist circumference, total cho-
lesterol, LDL-C, TG, and 2-h PG between clinically hypothyroid sub-
jects and the euthyroid group. Subclinical hyperthyroid subjects
had significant higher FBS values than the euthyroid group. Clini-
cally hyperthyroid subjects had significantly lower values of TG,
LDL-C, and HDL-C than the euthyroid group. Linear regression anal-
ysis showed positive associations for TSH with total cholesterol and
TG; in addition FT4 was associated with WC, BMI, DBP and serum
concentrations of TG, FBS and insulin after adjustment for age, sex
and smoking (▶Table 2).
The prevalence of MetS was significantly higher in clinical hypo-
thyroid subjects (41.6 %) than in other groups (p < 0.05); among
MetS components, abdominal obesity (45.9 %) and hypertriglyce-
mia (58 %) had significant higher prevalence in the same group. The

194 Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
 ▶Table 2 Association of TSH and FT4 levels with metabolic parameters.

Model TSH (mU/l) FT4 (ng/dl)

β R² p-Value β R² p-Value

WC (cm) 1 0.005 0.000 0.72 − 1.91 0.004 < 0.001

2 0.012 0.184 0.34 − 1.48 0.186 < 0.001

TC (mg/dl) 1 0.24 0.004 < 0.001 − 15.23 0.019 < 0.001
2 0.23 0.192 < 0.001 − 10.92 0.198 < 0.001
TG (mg/dl) 1 0.001 0.001 0.026 − 0.09 0.004 < 0.001
2 0.002 0.130 0.003 − 0.089 0.133 < 0.001
HDL-C (mg/dl) 1 − 0.004 0.000 0.73 − 0.86 0.001 0.017
2 − 0.017 0.104 0.13 0.44 0.104 0.20
FBS (mg/dl) 1 − 0.048 0.000 0.13 0.16 0.000 0.87
2 − 0.044 0.099 0.15 1.76 0.099 0.06
SBP (mmHg) 1 − 0.022 0.000 0.27 − 0.65 0.000 0.28
2 − 0.014 0.26 0.42 0.60 0.261 0.25

Downloaded by: Boston University. Copyrighted material.

DBP (mmHg) 1 − 0.001 0.000 0.93 − 1.45 0.003 < 0.001
2 0.001 0.106 0.92 − 0.90 0.107 0.009
BMI (kg/m2) 1 0.008 0.000 0.09 − 1.22 0.012 < 0.001
2 0.006 0.100 0.18 − 0.77 0.104 < 0.001
Fasting serum insulin 1 0.000 0.000 0.61 − 0.066 0.002 < 0.001
(mIU/l)
2 − 0.001 0.027 0.30 − 0.044 0.028 0.015
HOMA-IR 1 − 0.001 0.000 0.25 − 0.065 0.002 0.001
2 − 0.001 0.021 0.12 − 0.031 0.021 0.13

Values of β are unstandardized regression coefficients; values of R² are adjusted R square

Model 1: Crude model; Model 2: Adjusted for age, sex, and smoking; WC: Waist circumference; TC: Total cholesterol; lipoprotein; TG: Triglyceride;
HDL-C: High-density lipoprotein; FBS: Fasting blood sugar; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; HOMA-IR: Homeostasis model
assessment for insulin resistance; TSH: Thyroid stimulating hormone; FT4: Free thyroxin

prevalence of hyperglycemia was highest in subclinical hyperthy-
roid subjects (31.3 %, p < 0.001) (▶ Table 3).
Logistic regression analysis showed the odds of 1.6 (1.1, 2.3) for
prevalent MetS in clinically hypothyroid subject; however, the sig-
nificance disappeared after adjustment for age, sex and smoking.
Significant odds ratios were observed for the prevalent abdominal
obesity [OR: 2.1, %95 CI: 1.4, 3.1, p < 0.001] and hypertriglyceri-
demia [OR: 1.8, 95 % CI:1.2–2.6, p < 0.05]. In sex-split analysis, sig-
nificant odds ratio for prevalent MetS was observed only in clinical-
ly hypothyroid men [OR: 2.9, 95 % CI: 1.04, 8.4, p = 0.04] after ad-
justments for age and smoking (▶ Table 4). After further
adjustment for BMI, the significance had disappeared . In men,
overt hypothyroidism was associated with higher odds of MetS in
crude model and after adjustment for age and smoking. In women,
the association between overt hypothyroidism and MetS was mar-
ginally significant only in the crude model [OR: 0.068, 95 % CI:
0.97–2.42, p = 0.06)] (▶Table 5).
In age-split analysis ( <  50 years and ≥ 50 years), the risk of Mets
was significantly higher in over 50 subclinical hypothyroid subjects
even after adjustment for sex, smoking, and BMI [OR: 1.76, 95 % CI
(1.04–2.97]. In both smokers and non-smokers, no significant as-
sociation was observed between MetS and any of the thyroid func-
tion groups. Odds ratio for MetS was calculated based on the 2
waist circumference cut off points of 90 and 95 cm for definition of
MetS, although no difference was observed.
Overt and subclinical hyperthyroidism had significantly higher
odds of hyperglycemia in men and women after full adjustment for
age, smoking, and BMI (▶ Table 4, 5). Subclinical hyperthyroidism
increased the risk of hyperglycemia in both smokers [OR: 4.34, 95 %
CI: 1.59–11.86] and nonsmokers [OR: 1.52, 95 % CI: 1.03–2.23].
In total 683 ( %12.6) of subjects were TPOAb positive. In sub-
group analysis in TPOAb negative subjects, no association was ob-
served between thyroid function groups and MetS. Subclinically
hyperthyroid patients had significantly higher odds of hyperglyce-
mia, even after exclusion of TPO positive patients.

Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200 195
 Endocrine Care
▶Table 3 Comparison of prevalence of metabolic syndrome and its components in thyroid function groups.
Euthyroid Overt
­hypothyroidism
MetS n ( %) 1 481 (31.2) 42 (41.6) *
Abdominal obesity ( %) 29.1 45.9†
Hypertriglyceridemia ( %) 44.0 58.0 *
Reduced HDL-C level ( %) 72.0 76.8
Hyperglycemia ( %) 19.4 20.4
Hypertension ( %) 28.7 30.2
p-Values are for comparison with euthyroid subjects; * p < 0.05; † p < 0.001
HDL-C: High-density lipoprotein cholesterol; Mets: Metabolic syndrome
Abdominal obesity: Waist circumference ≥ 95 cm; Hypertriglyceridemia: Triglyceride ≥ 150 mg/dl or specific treatment; Reduced HDL-C: High density
lipoprotein cholesterol < 40 in males and < 50 mg/dl in women or specific treatment; Hyperglycemia: Fasting plasma glucose ≥ 100 mg/dl or treatment;
Hypertension: Systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg or specific treatment
Discussion
This study showed that overt, but not subclinical hypothyroidism,
may be associated with higher risk of MetS and 2 of its components;
that is, abdominal obesity and hypertriglyceridemia; elderly sub-
jects with subclinical hypothyroidism had higher risk of MetS. Hy-
perthyroidism was associated with impaired fasting glucose.
Dyslipidemia, a feature of MetS, is common in patients with thy-
roid dysfunction especially overt hypothyroidism, mostly present-
ing with high LDL-C and total cholesterol. Regarding TG and HDL-
C, existing data are scarce, reporting higher or similar results in eu-
thyroid subjects [16]. For subclinical hypothyroidism, results are
mostly contradictory, with majority of studies demonstrating no
difference regarding HDL-C and TG, while others showed higher
values in subclinical forms. We found significant negative associa-
tions of free T4 with TG and LDL-C and positive association of TSH
with TG and LDL-C; higher TG and LDL-C values were found only in
overt but not subclinical hypothyroid subjects. HDL-C levels did not
differ between euthyroid and hypothyroid subjects.
The effects of thyroid hormones on all aspects of lipid metabo-
lism pathways may induce lipid abnormalities in thyroid dysfunc-
tion especially in hypothyroidism [17]. Normal or high levels of TGs
in hypothyroidism are due to normal or decreased lipoprotein li-
pase activity in the adipose tissue and decreased hepatic lipase ac-
tivity [17–19]. Thyroid hormones affect HDL-C through cholester-
yl ester transfer protein, hepatic lipase activity and inhibit gene ex-
pression through competitive action in binding to thyroid hormone
receptors resulting HDL-C values to be increased in hyperthyroid-
ism or decreased in hypothyroidism [1, 20]. Furthermore, coexist-
ence of thyroid dysfunction with other biochemical abnormalities,
such as oxidative stress and insulin resistance, may induce dyslipi-
demia, through a vicious cycle [21–23].
We observed higher values in BMI and even WC (another MetS
feature) in clinically hypothyroid subjects. FT4, contrary to TSH,
was associated with WC. Thyroid dysfunction is reported to affect
BMI; overt hypothyroidism is associated with weight gain, where-
as hyperthyroidism results in weight loss due to the catabolic ef-
196
Subclinical Overt Subclinical
­hypothyroidism ­hyperthyroidism ­hyperthyroidism
90 (30.6) 30 (36.6) 61 (34.3)
26.4 29.6 33.7
40.8 40.2 45.5
74.1 79.3 74.0
19.5 27.2 31.3†
28.2 29.6 28.3
Downloaded by: Boston University. Copyrighted material.
fects of excess levels of thyroid hormones. The association of sub-
clinical hypothyroidism with obesity has been reported [24]. Serum
TSH values, even within the normal ranges, were associated with
BMI [25]. In NHANES, BMI and WC were positively associated with
TSH and free T3, but not FT4 concentrations [26]. Prior studies have
reported that obese patients have slightly higher TSH levels as com-
pared to normal weight patients; in addition, T3 levels may be in-
creased but T4 levels unchanged. In studies of weight loss in obese
and weight gain in anorectic patients, inverse associations between
TSH and FT3 with BMI were observed [27, 28]. After weight loss, T3
levels return to normal, findings suggesting that weight gain and
obesity result in changes in the thyroid function, rather than
change in thyroid function being the primary event leading to obe-
sity. It is not known whether the increase in TSH and T3 levels are
related or if they represent independent results of obesity. BMI may
not represent adipose mass distribution and visceral obesity is the
key element in the development of MetS. Regarding body fat dis-
tribution, none of the population studies have investigated the re-
lationship between central fat accumulation and thyroid function,
except one, which reported visceral obesity to be the best predic-
tor of TSH levels [29].
In the present study, dysglycemia was observed in hyperthyroid
subjects in all sex and age groups, even in TPOAb negative subjects.
Two-hour PPG was significantly higher in overt hypothyroid group.
Other reports in this regard are contradictory. Studies showed im-
paired glucose tolerance and insulin response to oral glucose tol-
erance test in overt and subclinically hyperthyroid and hypothyroid
subjects [21, 30], suggesting the occurrence of insulin resistance
in both hypo- and hyperthyroid states. Hypothyroidism is an insu-
lin-resistant state associated with decreased glucose transport in
myocyte by mediating glucose transporter 5 (GLUT5). In hyperthy-
roidism, increased gluconeogenesis and decreased glycogen syn-
thesis are mediated by increased GLUT 1,3,4 [31, 32]. Similar to our
findings, higher insulin levels and lower insulin clearance have been
reported in hypothyroidism as in one study [33]. There is no strong
Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
 ▶Table 4 Odds of prevalence of Mets and its components by thyroid function groups in men.

Model MetS Abdominal obesity Hyper-triglyceridemia Reduced HDL-C Hyperglycemia Hypertension

Overt hypothyroidism 1 3.43 (1.26–9.30) * 3.07 (1.17–8.11) * 3.16 (1.03–9.71) * 1.13 (0.40–3.22) 1.59 (0.56–4.53) 1.95 (0.75–5.07)

2 2.97 (1.04–8.46) * 2.72 (1.01–7.34) * 2.76 (0.89–8.59) 1.12 (0.39–3.20) 1.15 (0.37–3.58) 1.60 (0.56–4.63)
3 2.14 (0.66–6.91) 1.73 (0.39–7.64) 2.06 (0.63–6.67) 0.88 (0.30–2.59) 0.97 (0.31–3.03) 1.32 (0.45–3.87)
Subclinical hypothyroidism 1 0.98 (0.60–1.61) 1.43 (0.88–2.33) 0.92 (0.57–1.48) 0.90 (0.55–1.49) 1.04 (0.58–1.86) 0.70 (0.40–1.22)
2 1.01 (0.60–1.70) 1.47 (0.90–2.42) 0.95 (0.58–1.53) 0.92 (0.56–1.52) 1.11 (0.60–2.06) 0.69 (0.38–1.24)
3 1.04 (0.56–1.92) 2.46 (1.14–5.32) * 0.99 (0.59–1.67) 0.96 (0.57–1.61) 1.13 (0.61–2.10) 0.69 (0.38–1.26)
Overt hyperthyroidism 1 1.16 (0.58–2.32) 1.03 (0.50–2.12) 0.82 (0.42–1.60) 1.59 (0.72–3.51) 0.99 (0.43–2.28) 0.79 (0.37–1.70)
2 1.14 (0.56–2.36) 1.02 (0.49–2.12) 0.73 (0.37–1.46) 1.49 (0.67–3.31) 0.98 (0.41–2.35) 0.78 (0.35–1.76)
3 1.57 (0.68–3.61) 2.26 (0.77–6.66) 0.79 (0.38–1.65) 1.61 (0.72–3.65) 1.05 (0.43–2.54) 0.85 (0.37–1.95)
Subclinical hyperthyroidism 1 1.32 (0.82–2.15) 2.21 (1.38–3.56) * 1.00 (0.62–1.60) 0.98 (0.59–1.63) 2.34 (1.43–3.82) * 0.72 (0.41–1.25)
2 0.99 (0.59–1.65) 1.84 (1.13–3.00) * 0.84 (0.52–1.37) 1.00 (0.60–1.66) 1.77 (1.04–3.01) * 0.46 (0.25–0.83) *
3 0.85 (0.48–1.50) 2.29 (1.12–4.71) * 0.75 (0.45–1.25) 0.93 (0.56–1.57) 1.71 (1.00–2.93) * 0.43 (0.23–0.78) *

Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
* p < 0.05; Model 1: Crude, Model 2: Adjusted for age and smoking; Model 3: Adjusted for age, smoking, and BMI

▶Table 5 Odds of prevalence of Mets and its components by thyroid function groups in women.

Model MetS Abdominal obesity Hyper-triglyceridemia Reduced HDL-C Hyperglycemia Hypertension

Overt hypothyroidism 1 1.53 (0.97–2.42) p = 0.068 2.06 (1.32–3.23) * 1.89 (1.22–2.93) * 1.17 (0.69–2.00) 1.02 (0.58–1.81) 1.00 (0.61–1.67)

2 1.12 (0.66–1.89) 1.72 (1.05–2.80) * 1.47 (0.91–2.37) 1.16 (0.68–1.97) 0.76 (0.41–1.39) 0.66 (0.37–1.17)
3 0.83 (0.48–1.44) 1.05 (0.54–2.05) 1.23 (0.75–1.99) 1.08 (0.63–1.85) 0.68 (0.37–1.25) 0.57 (0.32–1.01) *
Subclinical hypothyroidism 1 1.04 (0.77–1.40) 0.76 (0.55–1.07) 0.99 (0.75–1.32) 1.09 (0.79–1.50) 1.05 (0.74–1.49) 1.16 (0.85–1.56)
2 1.01 (0.71–1.45) 0.73 (0.50–1.06) 0.98 (0.71–1.34) 1.09 (0.79–1.50) 0.99 (0.67–1.46) 1.18 (0.82–1.69)
3 0.99 (0.67–1.48) 0.68 (0.41–1.11) 0.98 (0.70–1.36) 1.07 (0.77–1.49) 0.96 (0.64–1.44) 1.17 (0.80–1.71)
Overt hyperthyroidism 1 1.37 (0.75–2.50) 1.04 (0.54–1.97) 0.90 (0.50–1.65) 1.39 (0.67–2.90) 2.11 (1.13–3.92) * 1.30 (0.70–2.42)
2 1.48 (0.73–3.01) 1.02 (0.50–2.59) 0.88 (0.45–1.70) 1.42 (0.68–2.94) 2.40 (1.20–4.79) * 1.35 (0.65–2.79)
3 1.70 (0.81–3.58) 1.34 (0.54–3.30) 0.90 (0.46–1.76) 1.43 (0.69–2.97) 2.53 (1.26–5.08) * 1.44 (0.69–3.00)
Subclinical hyperthyroidism 1 1.06 (0.70–1.62) 0.77 (0.48–1.23) 1.15 (0.77–1.71) 1.19 (0.74–1.91) 1.63 (1.05–2.55) * 1.23 (0.81–1.89)
2 0.87 (0.54–1.41) 0.65 (0.39–1.07) 1.01 (0.66–1.54) 1.19 (0.75–1.91) 1.54 (0.96–2.49) 1.08 (0.67–1.75)
3 1.12 (0.67–1.86) 1.07 (0.56–2.05) 1.15 (0.74–1.79) 1.26 (0.78–2.04) 1.72 (1.06–2.80) * 1.25 (0.76–2.05)

* p < 0.05; Model 1: Crude; Model 2: Adjusted for age and smoking; Model 3: Adjusted for age, smoking and BMI

197
Downloaded by: Boston University. Copyrighted material.
 Endocrine Care
evidence for any effects of thyroid hormones on insulin resistance
and serum glucose levels.
In the present study, no correlation was found between high BP
and thyroid function. The most studies reported a high prevalence
of hypertension in hypothyroidism. The mechanism of increased
blood pressure in hypothyroidism is not clearly known; however,
acceleration of structural change of vascular tissue due to thyroid
hormone deficiency may be responsible for higher peripheral vas-
cular resistance [34].
Furthermore, alteration of autonomic nervous function by thy-
roid hormone deficiency could cause hemodynamic changes. In-
creases in plasma norepinephrine concentration mainly due to an
increased secretion rate, rather than decreased metabolism of nor-
epinephrine have been demonstrated in hypothyroid patients [35].
High serum prolactin and TSH concentrations, seen in patients with
hypothyroidism, suggest reduced dopaminergic activity in the cen-
tral nervous system [36] that could contribute to the development
of hypertension by enhancing norepinephrine release. Ittermann
et al. reported a positive relationship between serum TSH levels
and hypertension in children and adolescents, suggesting that sub-
clinical hypothyroidism is associated with an increased risk of hy-
pertension [37]. A recant meta-analysis documented a weak asso-
ciation for SCH with increased SBP or DBP and no association for
sub-overt hyperthyroidism [37]; however, treatment with thyroid
hormones showed no change is SBP or DBP.
Regarding the association of MetS (as a whole entity) and thy-
roid dysfunction, most studies have focused on subclinical forms
of thyroid dysfunction, whereas surprisingly none have assessed
the association of MetS with overt hypothyroidism. In the current
study, abdominal obesity and dyslipidemia were more prevalent in
the clinically hypothyroid group and overt hypothyroidism was a
significant predictor of MetS, only in men, a gender difference may
be due to the fact that most women in this study are under meno-
pausal age (77 %), with mean age of 39.2 ± 13; therefore, the ad-
vantageous effects of estrogen in this age group may inhibit pro-
gression to MetS in clinically hypothyroid women; in other words,
menopause may interact with the effect of thyroid hormones on
metabolic abnormalities. A review article reported higher insulin
resistance in men compared to women due to greater amounts of
visceral and hepatic adipose tissue and lack of the protective effect
of estrogen [38], results consistent with those of our previous sur-
vey [39]. A review of 30 population based studies in Europe showed
a larger casual effect of adiposity on fasting insulin in men, com-
pared to women and sex heterogeneity in the effect of adiposity
on CVD risk factors, which could have been a result of differences
in adipose endocrine function [40, 41]. On the other hand, BMI in
women (27.7 ± 4.8) was significantly higher than in men (25.7 ± 4.1),
p < 0.001; the higher TSH levels could be related to obesity rather
than a true hypothyroid state, which could explain the lack of asso-
ciation with MetS in women. After age splitting, the risk of Mets
was significantly higher only in subclinically hypothyroid subjects
aged > 50 even after adjustments for sex, smoking, and BMI, indi-
cating that subclinical hypothyroidism in the elderly is associated
with higher risk of Mets, independent of sex and BMI and smoking.
A few studies have shown the association of MetS with subclinical
hypothyroidism. Lee et al. [25] reported a significant increase in
the number of the MetS components with increasing TSH values in
198
7 270 euthyroid subjects and demonstrated that participants with
high-normal TSH levels had a 2-fold higher risk of MetS, findings
similar to those of Park et al. of 6 000 euthyroid women, which in-
cluded the subclinical forms [42]. In a large population-based study
of older adults (the health ABC study) [7], thyroid dysfunction had
significant impact on all MetS components, except WC, increasing
TSH levels were associated with greater odds of prevalent but not
incident MetS. The longitudinal Aging Amsterdam Study of a rep-
resentative sample of 1 178 older Dutch persons, aged 65–88 years
[43], reported that subjects with a serum TSH in the upper quartile
had a higher prevalence of MetS compared to subjects with a serum
TSH in the lowest quartile; however in this survey only older sub-
jects and subclinical thyroid dysfunction were investigated. A re-
cent study in Taiwan [44] showed that even slight increases in TSH,
as in subclinical hypothyroidism, may be a risk factor for MetS; lipid
profiles were more affected by subclinical hypothyroidism, hence
would result more often in MetS than subclinical hyperthyroidism.
In contrast to the above mentioned surveys, our large-scale
study demonstrated no significant associations between subclini-
cal thyroid diseases and MetS prevalence except in the elderly,
Downloaded by: Boston University. Copyrighted material.
which may be due to the fact that a hypothyroid state in aging pop-
ulations could be considered as a part of the physiological and
aging process and not a pathological state, as what happens in hy-
pertension. Investigators also believe that large-scale studies of
healthy subjects analyzing too many clinical and laboratory data
could reveal possible relationships between subclinical thyroid dis-
ease and MetS. Supporting results of the present study, a 2009
cross-sectional study on 9 055 healthy subjects in Taiwan found no
statistical correlation between subclinical thyroid diseases and
MetS [45]. In another large-scale study, although MetS prevalence
was similar in euthyroid individuals and those with subclinical thy-
roid disease, low thyroid function, even in euthyroid subjects, pre-
disposed subjects to higher glucose, insulin, and HOMA-IR levels
[46].
Regarding hyperthyroid states, as it is associated with hyper-
metabolic state, as we found MetS is less likely to occur as what we
observed; however, a dysmetabolic state of hyperglycemia was ob-
served in hyperthyroidism. Overt and subclinical hyperthyroidism
induced high risk for hyperglycemia in all sex, age and smoking
groups. Nonsignificance of the association of overt hyperthyroid-
ism in men with hyperglycemia is due to the low sample size in this
group and insufficient power of the analysis.
The strength of the current study is its large population-based
survey in an iodine sufficient area. The limitations of our study in-
clude its cross sectional design, which restricts conclusion for
cause–effect relationship; diet and exercise which impact the ex-
amined variables are not controlled. Overt hypothyroidism may be
overestimated by misplacing subclinical type in overt hypothyroid
group. Furthermore, due to the individual variation of thyroid hor-
mones within one subject, one measurement underestimates the
association between thyroid dysfunction and health outcomes [47].
Subclinical hypothyroidism is better to be considered in the el-
derly especially in those with risk of cardiovascular and metabolic
diseases. Future large cohort studies are needed with a sufficient
follow-up period to help determine the significance of early detec-
tion of thyroid dysfunction especially in subclinical forms and
longer term associations with MetS in different age and sex groups.
Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
Results of this study will add to global knowledge and will be espe-
cially applicable to Asian populations.
Authors’ Contribution
F. Azizi: Study design, supervision, interpretation, and writing the
manuscript; L. Mehran: Study design and performance, interpreta-
tion, and writing the manuscript; Amouzegar A: Interpretation and
writing the manuscript; P. Kheirkhah Rahimabad: Analysis and man-
uscript writing; G.Tahmasebinejad: Statistical analysis; M. Tohidi:
Lab measurements supervision and writing the manuscript.
Acknowledgements
The project supported by Research Institute of Endocrine Scienc-
es, Shahid Beheshti University of Medical Sciences, Tehran, I. R. Iran.
We would like to acknowledge the personnel of the laboratory of
Research Institute for Endocrine Sciences for their collaboration
and assistance. We also thank Ms. Niloofar Shiva for editing the
manuscript.
Conflict of Interest
The authors declare no conflict of interest.
References
[1] Liu YY, Brent GA. Thyroid hormone crosstalk with nuclear receptor
signaling in metabolic regulation. Trends Endocrinol Metab 2010; 21:
166–173
[2] Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet
2005; 365: 1415–1428
[3] Ferrannini E, Haffner SM, Mitchell BD, Stern MP. Hyperinsulinaemia:
the key feature of a cardiovascular and metabolic syndrome.
Diabetologia 1991; 34: 416–422
[4] Dimitriadis G, Baker B, Marsh H, Mandarino L, Rizza R, Bergman R et al.
Effect of thyroid hormone excess on action, secretion, and metabolism
of insulin in humans. Am J Physiol 1985; 248 (5 Pt 1): E593–E601
[5] Dimitriadis G, Mitrou P, Lambadiari V, Boutati E, Maratou E, Panagi-
otakos DB et al. Insulin action in adipose tissue and muscle in
hypothyroidism. J Clin Endocrinol Metab 2006; 91: 4930–4937
[6] Iwen KA, Schroder E. Brabant G. Thyroid hormones and the metabolic
syndrome. Eur Thyroid J 2013; 2: 83–92
[7] Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic
I et al. Thyroid function and prevalent and incident metabolic
syndrome in older adults: the Health, Ageing and Body Composition
Study. Clin Endocrinol (Oxf) 2012; 76: 911–918
[8] Ford ES. Risks for all-cause mortality, cardiovascular disease, and
diabetes associated with the metabolic syndrome: a summary of the
evidence. Diabetes Care 2005; 28: 1769–1778
[9] Thvilum M, Brandt F, Almind D, Christensen K, Hegedus L, Brix TH.
Excess mortality in patients diagnosed with hypothyroidism: a
nationwide cohort study of singletons and twins. J Clin Endocrinol
Metab 2013; 98: 1069–1075
[10] Azizi F, Amouzegar A, Delshad H, Tohidi M, Mehran L, Mehrabi Y.
Natural course of thyroid disease profile in a population in nutrition
transition: Tehran Thyroid Study. Arch Iran Med 2013; 16: 418–423
Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200
[11] Azizi F, Ghanbarian A, Momenan AA, Hadaegh F, Mirmiran P, Hedayati
M et al. Prevention of non-communicable disease in a population in
nutrition transition: Tehran Lipid and Glucose Study phase II. Trials
2009; 10: 5
[12] Delshad H, Amouzegar A, Mirmiran P, Mehran L, Azizi F. Eighteen years
of continuously sustained elimination of iodine deficiency in the
Islamic Republic of Iran: the vitality of periodic monitoring. Thyroid 22:
415–421
[13] Amouzegar A, Delshad H, Mehran L, Tohidi M, Khafaji F, Azizi D.
Reference limit of Thyrotropin (TSH) and free Thyroxine (FT4) in
thyroperoxidase positive and negative subjects: a population based
study. J Endocrinol Invest 2013; 36: 950–954
[14] Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA
et al. Harmonizing the metabolic syndrome: a joint interim statement
of the International Diabetes Federation Task Force on Epidemiology
and Prevention; National Heart, Lung, and Blood Institute; American
Heart Association; World Heart Federation; International Atherosclero-
sis Society; and International Association for the Study of Obesity.
Circulation 2009; 120: 1640–1645
[15] Azizi F, Khalili D, Aghajani H, Esteghamati A, Hosseinpanah F, Delavari
A et al. Appropriate waist circumference cut-off points among Iranian
adults: the first report of the Iranian National Committee of Obesity.
Arch Iran Med 2010; 13: 243–244
Downloaded by: Boston University. Copyrighted material.
[16] Duntas LH. Thyroid disease and lipids. Thyroid 2002; 12: 287–293
[17] Zhu X, Cheng SY. New insights into regulation of lipid metabolism by
thyroid hormone. Curr Opin Endocrinol Diabetes Obes 2010; 17:
408–413
[18] Abrams JJ, Grundy SM, Ginsberg H. Metabolism of plasma triglycerides
in hypothyroidism and hyperthyroidism in man. J Lipid Res 1981; 22:
307–322
[19] Lam KS, Chan MK, Yeung RT. High-density lipoprotein cholesterol,
hepatic lipase and lipoprotein lipase activities in thyroid dysfunction–
effects of treatment. Q J Med 1986; 59: 513–521
[20] Tancevski I, Wehinger A, Demetz E, Eller P, Duwensee K, Huber J et al.
Reduced plasma high-density lipoprotein cholesterol in hyperthyroid
mice coincides with decreased hepatic adenosine 5′-triphos-
phate-binding cassette transporter 1 expression. Endocrinology 2008;
149: 3708–3712
[21] Maratou E, Hadjidakis DJ, Peppa M, Alevizaki M, Tsegka K, Lambadiari
V et al. Studies of insulin resistance in patients with clinical and
subclinical hyperthyroidism. Eur J Endocrinol 2010; 163: 625–630
[22] Santi A, Duarte MM, Moresco RN, Menezes C, Bagatini MD, Schetinger
MR et al. Association between thyroid hormones, lipids and oxidative
stress biomarkers in overt hypothyroidism. Clin Chem Lab Med 2010;
48: 1635–1639
[23] Yavuz DG, Yuksel M, Deyneli O, Ozen Y, Aydin H, Akalin S. Association
of serum paraoxonase activity with insulin sensitivity and oxidative
stress in hyperthyroid and TSH-suppressed nodular goitre patients.
Clin Endocrinol (Oxf) 2004; 61: 515–521
[24] de Moura Souza A, Sichieri R. Association between serum TSH
concentration within the normal range and adiposity. Eur J Endocrinol
2011; 165: 11–15
[25] Lee YK, Kim JE, Oh HJ, Park KS, Kim SK, Park SW et al. Serum TSH level
in healthy Koreans and the association of TSH with serum lipid
concentration and metabolic syndrome. Korean J Intern Med 2011; 26:
432–439
[26] Kitahara CM, Platz EA, Ladenson PW, Mondul AM, Menke A. Berrington
de Gonzalez A. Body fatness and markers of thyroid function among
U.S. men and women. PLoS One 2012; 7: e34979
[27] Reinehr T, Isa A, de Sousa G, Dieffenbach R, Andler W. Thyroid
hormones and their relation to weight status. Horm Res 2008; 70:
51–57
199
 Endocrine Care
[28] Welt CK, Chan JL, Bullen J, Murphy R, Smith P, DePaoli AM et al.
Recombinant human leptin in women with hypothalamic amenorrhea.
N Engl J Med 2004; 351: 987–997
[29] Muscogiuri G, Sorice GP, Mezza T, Prioletta A, Lassandro AP, Pirronti T
et al. High-normal TSH values in obesity: is it insulin resistance or
adipose tissue’s guilt? Obesity (Silver Spring) 2013; 21: 101–106
[30] Jenkins RC, Valcavi R, Zini M, Frasoldati A, Heller SR, Camacho-Hubner
C et al. Association of elevated insulin-like growth factor binding
protein-1 with insulin resistance in hyperthyroidism. Clin Endocrinol
(Oxf) 2000; 52: 187–195
[31] Visser WE, Heemstra KA, Swagemakers SM, Ozgur Z, Corssmit EP,
Burggraaf J et al. Physiological thyroid hormone levels regulate
numerous skeletal muscle transcripts. J Clin Endocrinol Metab 2009;
94: 3487–3496
[32] Dimitriadis G, Maratou E, Alevizaki M, Boutati E, Psara K, Papasteriades
C et al. Thyroid hormone excess increases basal and insulin-stimulated
recruitment of GLUT3 glucose transporters on cell surface. Horm
Metab Res 2005; 37: 15–20
[33] Stanicka S, Vondra K, Pelikanova T, Vlcek P, Hill M, Zamrazil V. Insulin
sensitivity and counter-regulatory hormones in hypothyroidism and
during thyroid hormone replacement therapy. Clin Chem Lab Med
2005; 43: 715–720
[34] Guyton AC. The relationship of cardiac output and arterial pressure
control. Circulation 1981; 64: 1079–1088
[35] Coulombe P, Dussault JH, Walker P. Plasma catecholamine concentra-
tions in hyperthyroidism and hypothyroidism. Metab Clin Exp 1976;
25: 973–979
[36] Feek CM, Sawers JS, Brown NS, Seth J, Irvine WJ, Toft AD. Influence of
thyroid status on dopaminergic inhibition of thyrotropin and prolactin
secretion: evidence for an additional feedback mechanism in the
control of thyroid hormone secretion. J Clin Endocrinol Metab 1980;
51: 585–589
[37] Ittermann T, Thamm M, Wallaschofski H, Rettig R, Volzke H. Serum
thyroid-stimulating hormone levels are associated with blood pressure
in children and adolescents. J Clin Endocrinol Metab 2012; 97:
828–834
200
[38] Geer EB, Shen W. Gender differences in insulin resistance, body
composition, and energy balance. Gend Med 2009; 6 (Suppl 1): 60–75
[39] Amouzegar A, Kazemian E, Gharibzadeh S, Mehran L, Tohidi M, Azizi F.
Association between thyroid hormones, thyroid antibodies and insulin
resistance in euthyroid individuals: A population-based cohort.
Diabetes Metab 2015; 41: 480–488
[40] Lear SA, Chen MM, Birmingham CL, Frohlich JJ. The relationship
between simple anthropometric indices and C-reactive protein: ethnic
and gender differences. Metabolism 2003; 52: 1542–1546
[41] Rossi IA, Bochud M, Bovet P, Paccaud F, Waeber G, Vollenweider P et al.
Sex difference and the role of leptin in the association between
high-sensitivity C-reactive protein and adiposity in two different
populations. Eur J Epidemiol 2012; 27: 379–384
[42] Oh JY, Sung YA, Lee HJ. Elevated thyroid stimulating hormone levels
are associated with metabolic syndrome in euthyroid young women.
Korean J Intern Med 2013; 28: 180–186
[43] Heima NE, Eekhoff EM, Oosterwerff MM, Lips PT, van Schoor NM,
Simsek S. Thyroid function and the metabolic syndrome in older
persons: a population-based study. Eur J Endocrinol 2013; 168: 59–65
[44] Lai Y, Wang J, Jiang F, Wang B, Chen Y, Li M et al. The relationship
between serum thyrotropin and components of metabolic syndrome.
Endocr J 2011; 58: 23–30
Downloaded by: Boston University. Copyrighted material.
[45] Wang CY, Chang TC, Chen MF. Associations between subclinical
thyroid disease and metabolic syndrome. Endocr J 2012; 59: 911–917
[46] Garduno-Garcia Jde J, Alvirde-Garcia U, Lopez-Carrasco G, Padilla
Mendoza ME, Mehta R, Arellano-Campos O et al. TSH and free
thyroxine concentrations are associated with differing metabolic
markers in euthyroid subjects. Eur J Endocrinol 2010; 163: 273–278
[47] van de Ven AC, Netea-Maier RT, Medici M, Sweep FC, Ross HA, Hofman
Aet al. Underestimation of effect of thyroid function parameters on
morbidity and mortality due to intra-individual variation. J Clin
Endocrinol Metab 2011; 96: E2014–E2017
Mehran L et al. Thyroid and Metabolic Syndrome … Horm Metab Res 2017; 49: 192–200