REVIEW

CURRENT
OPINION Thyroid disease and the metabolic syndrome
Ladan Mehran, Atieh Amouzegar, and Fereidoun Azizi

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.
Keywords
free thyroxine, free triiodothyronine, metabolic syndrome, thyroid hormones, thyroid stimulating hormone

INTRODUCTION To sum-up the data available, in the current

Thyroid dysfunction and metabolic syndrome review we searched and collected the most recent
(MetS) are among the most common endocrine evidence regarding the association of thyroid func-
disorders associated with significant morbidity tion with MetS and its components.
and mortality [1,2]. Accumulated evidence postu-
lates that thyroid function disturbances affect lipid LOW NORMAL THYROID FUNCTION AND
and glucose metabolism, blood pressure (BP) and METABOLIC SYNDROME
body weight, all of which are associated with various
Several studies report conflicting results regarding
metabolic parameters and may therefore lead to the
the association between thyroid hormones and
development or aggravation of MetS components
MetS in euthyroid individuals [13–24]; mostly
[3]. The pathogenesis of MetS has closely been
assess MetS components individually [25] rather
linked to insulin resistance and obesity [4,5] both
than the syndrome as a whole entity [26–31].
of which are affected by thyroid hormones [6].
Most reports address the association of MetS com-
Coexistence of MetS and thyroid dysfunction may
ponents with serum thyroid stimulating hormone
aggravate their common metabolic features espe-
(TSH) levels [14,17,19,25,28,29,32–41], after which
cially in overt hypothyroid states strongly impact-
they focus on free thyroxine [freeT4 (FT4)]
ing the health of populations regarding
[16,19,28,30,31,35,37,38,42–45]. Relatively fewer
cardiovascular and metabolic risk factors, especially
studies have evaluated free triiodothyronine levels
in the elderly. Evidence available is more controver-
[free T3 (FT3)] or FT3/FT4 ratio [31,42,44,46–
sial for subclinical or low normal thyroid function. && &&
49,50 ,51,52 ,53]. Most studies however have
The link between thyroid autoimmunity and
MetS/insulin resistance is also not yet well defined,
due to lack of evidence [7,8] even in obese individ- Endocrine Research Center, Research Institute for Endocrine Sciences,
Shahid Beheshti University of Medical Sciences, Tehran, Iran
uals [9]. Inflammation has been suggested as one of
Correspondence to Fereidoun Azizi, Professor of Internal Medicine and
the mechanisms in MetS, although there is no evi-
Endocrinology, Endocrine Research Center, Research Institute for Endo-
dence on the direct effect of thyroid function on crine Sciences, Shahid Beheshti University of Medical Sciences, PO Box
inflammatory markers for example high-sensitivity 19395-4763, Tehran, Iran. Tel: +98 21 22432503;
&&
C-reactive protein (hsCRP) and IL-6 [10,11 ] or the fax: +98 21 22402463; e-mail: azizi@endocrine.ac.ir
association of thyroid antibodies with inflammatory Curr Opin Endocrinol Diabetes Obes 2019, 26:256–265
&&
markers [11 ,12]. DOI:10.1097/MED.0000000000000500

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KEY POINTS
 Subclinical hypothyroidism and even low normal
thyroid function are associated with the risk of various
metabolic abnormalities; however, the risk of MetS
remains a controversial issue.
 The complex interrelation between thyroid hormones
and metabolic parameters might be affected by age,
sex, BMI, insulin resistance, smoking, alcohol
consumption, iodine intake and inflammatory markers.
 Screening and treatment of mild thyroid hypofunction
may be warranted due to its adverse metabolic effects.
 The hyperthyroid state may be associated with insulin
resistance and dysglycemia.
 Autoimmune thyroid disease may be a potential risk
factor for metabolic abnormalities, even in those with
low normal thyroid stimulating hormone ranges.
cross-sectional design and longitudinal studies are
needed for clarification of causality and the effect of
changes in thyroid hormones on MetS incidence
&& &&
[27,54,56 ,57,58 ]. Tables 1 and 2 summarize the
results of cross-sectional and cohort studies that have
evaluated the association of thyroid hormones and
Mets in euthyroid individuals. Differences in ages,
ethnicity, sex composition, study designs, definitions
of thyroid hormone cut-offs and MetS and adjust-
ments may be also related to inconsistent results.
Cross-sectional studies
In most studies higher serum TSH levels were asso-
ciated with less favorable metabolic phenotypes or
MetS [13,14,21–24,29,30,35]; however, a number of
surveys found no association [15,19]; considering
FT4 the reports showed more disagreement
&&
[16,19,52 ,59,60]. We found lower normal FT4 lev-
els to be associated with a higher risk of insulin
resistance and MetS [19], results in line with those
of PREVEND study [28] and a large study in Korea
[16], although the latter found no association with
MetS, after age adjustment. A number of studies
&&
found either just a sex-specific association [52 ]
or observed no association between FT4 and meta-
bolic components [16,34,49,61].
Much data is available on the positive associa-
tion of FT3 with BMI, insulin resistance and meta-
&
bolic components [34,44,62,63,64 ]. Roef et al. [31]
observed that higher FT3, lower FT4 levels and
hence a higher FT3/FT4 ratio are associated with
various unfavorable metabolic profiles and cardio-
vascular diseases (CVD), results in line with those of
&&
Park et al. [50 ], Kim et al. [31,46] and Huang and
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Thyroid disease and the metabolic syndrome Mehran et al.
Hwang [15]. A large study from the Netherlands
conducted on 26 719 participants showed that com-
pared with the lowest, the highest FT3 and FT3/FT4
quartiles were associated with a 50–80% increased
&&
risk of having MetS [52 ].
The paradoxical association of FT3 and FT4 may
be justified by the results of a recent Mendelian
randomization study [87] in which children with
a genetically higher BMI had higher FT3 but not FT4,
suggesting the role of higher fat mass in increasing
FT3; however, genetic associations between FT3 and
MetS have not been explored in adults. Increased
conversion of FT4 to FT3 in obese individuals might
be related to increased deiodinase activity (DIO2) in
central obesity [44,65], as a compensatory mecha-
&
nism to prevent fat accumulation [64 ]. Therefore,
the FT3/FT4 ratio might be considered as a surrogate
marker of DIO2 activity reflecting the interaction of
TSH and thyroid hormones with metabolic param-
eters. On the whole, a positive association between
FT3 and unfavorable metabolic markers may be a
consequence of obesity rather than a cause of it
[44,49]. On the other hand, a recent Mendelian
study found no association between TSH or FT4
&
and insulin resistance/diabetes [66 ], despite the
increasing evidence on this issue. Considering insu-
lin resistance and obesity as the hallmarks of MetS,
the reverse concern arises whether MetS could be
responsible for increasing FT3. Based on current
evidence, the association between FT3 and MetS
may be bidirectional. Therefore, designing further
studies to verify the directionality of the association
and to explore genetic associations between FT3 and
MetS in adults is recommended.
Cohort studies
There have been only four prospective studies
assessing the association of thyroid hormones and
MetS incidence in euthyroid individuals (Table 2)
with mean follow-up periods ranging from 2 to 11
years. We, for the first time found that the cumula-
tive effect of decreasing FT4 values (not TSH) over
10 years was predictive for MetS incidence and its
three components that is abdominal obesity, high
triglyceride, and high BP adjusting for age, sex, BMI,
smoking and homeostatic model assessment-insulin
resistance (HOMA-IR) indicating the role of other
mechanisms, rather than BMI and insulin resistance
&&
[56 ]. In Korea, higher FT3/FT4 ratio was associated
with risk of MetS parameters and insulin resistance
&&
[50 ]; however, the study was hospital-based not
population-based and conducted in an area with
excess iodine intake. In USA, higher TSH was posi-
tively associated with increased odds ratio of the
prevalent but not incident MetS in the elderly;
www.co-endocrinology.com 257
 Table 1. Cross-sectional studies on the association of thyroid hormones with metabolic syndrome in euthyroid individuals

258
First author (year) Sample Mean age Country Setting Method Other findings Adjusted confounders Insulin resistance Metabolic syndrome
Thyroid

size (year)
Lin (2005) [18] 4938 50  12 Taiwan Hospital-based RIA TSH and T3 not measured Sex, age splitted No report FT4 associated
Roos (2007) [28] 1581 40  10 The Netherland Community-based ELIZA T3 not measured. FT4 was Age, sex HOMA-IR TSH not associated FT4 is FT4 associated
related to four of five MetS associated
traits
Park (2009) [24] 2205 58  6 Korea Postmenopausal women IRMA – Age, YSM, BMI, HOMA- No association TSH associated FT4 not
self-referred for IR, life style factors associated
routine check up
Ruhla (2010) [29] 1333 51  4 Germany Nonrandom volunteers ELISA Association of TSH in the upper Sex, age Weakly positive with TSH, TSH associated
normal range with obesity, omitted after excluding IGT
higher TG, and a 1.7-fold
increased likeliness for MetS
Garduno (2010) [30] 3184 42  10 Mexico Population-based RIA Negative association of FT4 and Age, sex FT4 negatively associated; TSH No association, FT3 not
WC, and positive with HDL; not associated assessed
positive association of TSH
with TC, TG and WC;

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combined use of FT4 and
TSH is recommended
Lai (2010) [17] 1534 44  13 China Community-based CML – Age, sex, HOMA-IR and No correlation No correlation
BMI
Lee (2011) [22] 7270 44  8 Korea Population-based CML – Sex, age, season, No report TSH associated
menopause status,
and obesity
Heima (2012) [14] 1187 75  6 The Netherland RIA IR not assessed T4 and t3 not assessed TSH associated
Oh (2013) [23] 2760 25  5 South Korea Young female volunteers – No correlation TSH associated
Mehran (2014) [19] 3724 38  13 Iran ECML FT4 associated with HDL-C, LDL- Age, sex and smoking, FT4 and TSH associated FT3 not assessed, FT4
C, TGs, WC, SBP, DBP BMI, HOMA-IR with IR associated
Roef (2014) [31] 2315 46  5 Belgium Population-based CML Association of higher FT3, lower Sex, age, height, and IR not assessed Association of FT3, FT4 and the
FT4 levels, and a higher current smoking status FT3/FT4 ratio to metabolic
FT3/FT4 ratio with weight or WC syndrome FT3: OR ¼ 1.3,
unfavorable metabolic profile FT4: OR ¼ 0.9; FT3/FT4
and CVD risk. Association of ratio: (OR ¼ 1.5)
FT3/FT4 ratio to IL6, hsCRP
Meng (2015) [53] 13 855 48  10 China Community-based CML – Age, sex split FT4 not associated Positive association of TSH and
FT3 with MetS
Kommareddy (2015) [41] 1005 46  15 USA Obese and overweight Not No associations between TSH Age, sex, race, education, TSH not associated FT4 and FT3 not assessed, TSH
mentioned and individual MetS socioeconomic status not associated
components and smoking
Laclaustra (2015) [45] 3533 49  8 Spain Male participants, workers CML – Age, alcohol intake and TSH associated Association of TSH and free T4
of the General Motors smoking with MetS
Kim (2016) [44] 13 496 50  6 Korea Health check-up program RIA – Sex, age, body fat TSH associated, T4 Independent association of T3
percentage, smoking, and T3 not levels and T3/T4 ratio with
HOMA-IR MetS
Park (2017) [48] 132 346 37  10 Korea Health check-up program RIA Association of MetS parameters Age, BMI, smoking, IR correlated with The FT3/FT4 a better predictor
and insulin resistance with menopausal status (in TSH and FT3/FT4 for MetS than TSH
TSH and FT3/FT4 ratio women)
Huang (2017) [15] 8207 44  10 Taiwan Voluntary health CML – Age, smoking, split for sex Not assessed High strong association of high
examination T3 with MetS, less stronger
with T4, TSH not associated

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&&
Wolffenbuttel (2017) [50 ] 26 719 46  13 The Netherland Population-based CML Association of FT3 with MetS Age, BMI, smoking, Not assessed 50–80% increased risk of MetS
parameters; association of alcohol IN highest FT3 and FT3/FT4
lower FT4 only in men quartile
&&
Raposoa (2019) [11 ] 486 59  14 Portugal Population-based CML TPOAb a negative association Age and sex FT3 associated with IR A positive association of FT3
with MetS OR: 0.5; and TG: and MetS; OR: 2.0
OR: 0.3

CVD, cardiovascular disease; FT3, free T3; FT4, freeT4; HDL-C, HDL cholesterol; HOMA-IR, homeostatic model assessment-insulin resistance; hsCRP, high-sensitivity C-reactive protein; IGT, impaired glucose tolerance; IR,
insulin resistance; LDL-C, LDL cholesterol; MetS, metabolic syndrome; OR, odds ratio; TC, total cholesterol; TG, triglyceride; TPOAb, thyroid peroxidase antibody; TSH, thyroid stimulating hormone; WC, waist

Volume 26  Number 5  October 2019

circumference; YSM, years of menopause.
 Thyroid disease and the metabolic syndrome Mehran et al.

however, participants with all ranges of TSH were

Association of decreasing FT4

values (not TSH) with MetS

FT3 levels as an independent

predictor for developing
included while thyroid hormones were not mea-

BP, blood pressure; CVD, cardiovascular diseases; HDL-C, HDL cholesterol; HOMA-IR, homeostatic model assessment-insulin resistance; MetS, metabolic syndrome; SCH, subclinical hypothyroidism; TG, triglyceride;
prevalent and incident

prevalent not incident

Association of TSH with

Association of TSH with

Metabolic syndrome
sured [67]. In China, increased serum FT3 level,
rather than FT4 and TSH was an independent pre-
dictor for developing MetS in euthyroid individuals.

incidence
Therefore, the interrelation between thyroid
MetS

MetS

MetS
hormones and metabolic parameters is complex
and has not yet been well elucidated. It is assumed
that variation in thyroid hormone homeostasis and
its association with metabolic parameters might be
affected by the different effects of age, sex and BMI
Insulin resistance

on thyroid metabolism.
associated

associated

Not assessed
FT4 and TSH

Cumulative effect of FT4 reduction Age, sex, BMI and HOMA-IR FT4 and TSH
No report

with IR

Sex impact
C, TG, SBP, FBS and FH of

Sex substantially affects MetS, thyroid function and

status, BMI, and HOMA-IR

baseline BMI, waist, HDL-

Age, sex, smoking, alcohol,
Age and sex; BMI, smoking

their associations [53,68–71] and striking differen-

Age, sex, race, smoking
Adjusted confounders

ces in the results of different studies may be due to

alcohol intake and

whether sex-split analysis or simple adjustment for

Table 2. Cohort studies on the association of thyroid hormones with metabolic syndrome in euthyroid individuals

sex are used. Sex disparity may be related to the

exercise

different effects of sex hormone on thyroid metab-

CVD

olism for example the effects of estrogen on TSH and

lipid profiles in women [72] in addition to postmen-
abdominal obesity, higher TG,

TSH and the incidence of MetS

mild SCH with increased odds

opausal effects [73] and the effect of low testosterone

over 10 years predictive for
cholesterol, TG, HDL-C, FBS

of prevalent MetS (OR: 2.3)

No associations between FT4,

Association between thyroid

levels on MetS parameters in men [74]. A genetic

SCH (TSH 10–20) not

basis for sex disparity has been also postulated [75].

Immunoassay Association of marked

high BP and MetS

function and BP,
Other findings

Age impact
The association between serum TSH and MetS may
differ in the elderly. A gradual decrease of FT3 levels
with increasing age was reported, while TSH and FT4
levels did not change significantly. It has been
follow-up time Method

CML

CML

reported that up to the age of 40 years, as TSH levels

RIA

increase, FT3/FT4 ratios increase; however, beyond

40 years the effect of TSH on T3 production is
2.9 years

Population based 9.6 years

blunted which may be due to reduced deiodinase

Black community 6 years

Population based 2 years

Mean

activity, development of TSH resistance with aging,

&&
or the combination of these [50 ,76]. Similar dis-
parity in the TSH-FT3 association was reported in
Hospital based

dwelling

aging rats [77].

Country Design

BMI impact
China
Korea

USA

It remains unclear whether obesity may influence

Iran

thyroid function or changes in thyroid function

Sample Mean age

38  13
(year)

may modulate body weight; however, as previously

45  9

73  3

45  3

mentioned both hypotheses have been validated

TSH, thyroid stimulating hormone.

through interventional studies. Decreased gene

5998

Waring (2012) [54] 2119

Mehran (2017) [53] 2393

6119

expression of TSH and FT3 receptors in visceral and

size

subcutaneous fat in obese individuals may be a com-

pensatory mechanism to cope with the peripheral
Park (2011) [27]

Gu (2018) [55]

resistance following hypertrophic changes in adipo-

First author

cytes, leading to increased TSH and FT3 levels [78];

(year)

vice versa insulin resistance in obese individuals

by causing compensatory hyper insulinemia may

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Thyroid
decrease DIO2 activity, simulating a hypothyroid
state [79].
A significant increase in TSH, but no differences
in FT3 and FT4 in obese individuals has been
reported [80], using direct measurements of insulin
resistance (euglycemic clamp) and body composi-
tion (computed tomography scan), suggesting the
role of increase in the visceral adipose tissue, and the
consequent insulin resistance. Controversial results
of earlier studies might be related to the use of
indirect methods for estimating insulin resistance
and adipose tissue, as BMI is not representative of fat
mass distribution and all obese/overweight individ-
uals are not inevitably insulin resistant, due to their
varying body compositions [81,82].
The impact of other confounders
Alcohol consumption and smoking have been less
considered in these studies despite their important
influence on MetS components for example possible
adverse effect of alcohol consumption on HDL cho-
lesterol (HDL-C), and BP [83–85] and smoking on
waist circumference and HDL-C levels [85]. Another
mechanism underlying the higher TSH and FT3/FT4
ratios in individuals with less favorable metabolic
profiles could be a lower iodine pool which has not
been considered in most studies.
HYPOTHYROIDISM AND METABOLIC
SYNDROME
Many studies report the association of subclinical
hypothyroidism (SCH) with obesity, worsened lipid
profiles, higher BP, and markers of systemic inflam-
mation, analogs to those observed in MetS [39,40];
however, reports including the results of two last
meta-analyses are contradictory [17,26,86–88]. These
&&
studies have cross-sectional design [30,89 ,90–94],
and mostly not having assessed MetS as a whole entity.
Only one cohort study of 66 822 Taiwanese partici-
pants, a significant increased risk of developing SCH
during 4 years follow-up was reported in MetS patients
&&
compared with non-MetS [95 ]. Table 3 summarizes
the results of studies on the association between SCH
and MetS.
There are controversies regarding insulin resis-
tance and glycemia in patients with thyroid dysfunc-
tion [30,96]. Decreased insulin sensitivity in overt
hypothyroidism (OH) has been reported [6,97–99], a
feature which may extend to subclinical or even
within physiological range [19,28]; insulin resistance
reported in SCH is comparable with that of OH,
suggesting that the lower the thyroid hormone levels,
the lower the sensitivity of tissues to insulin [96].
Fasting hyperinsulinemia with decreased or normal
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HOMA-IR has been reported in SCH [100]. In contrast
impaired glycemic control in type 2 people with
diabetes may herald the onset of thyroid dysfunction
&&
[101 ]; these effects may be due to decreased intra-
cellular glucose utilization, downregulation of glu-
cose transporters, decreased glycogen synthesis and
reduced glucose oxidation [6,96,102], indicating that
thyroid hypofunction leads to insulin resistance-
associated disorders such as CVD and Mets
[103,104]; these associations are reported to be
more obvious in the overt form of hypothyroidism,
rather than subclinical or low normal thyroid func-
tion; regarding MetS the results are more controver-
&&
sial [101 ].
The relationship of BMI with thyroid hormones
&
is well known [34,105–107,108 ], vice versa there
are evidences on reverting thyroid hormones to
&
normal levels following weight loss [65,109 ,110];
There is no evidence in favor of beneficial effects of
levothyroxine on body weight in obese individuals
having SCH with TSH less than 10 mU/l [111].
Observational studies also report the association
of SCH with high triglycerides, total cholesterol (TC)
and LDL cholesterol (LDL-C) even in mild SCH
[112,113]. Data regarding the effects of levothyrox-
ine therapy on lipid profiles in SCH patients were
heterogeneous and a few reported significant
improvement in lipid profile [114], in a recent
meta-analysis L-thyroxine significantly improved
LDL-C levels in patients with SCH, while not signif-
icantly affecting TC, triglycerides and HDL-C levels
[115].
Improvement in metabolic abnormalities in
SCH individuals following LT4 therapy have been
reported [116,117]; however, further clinical studies
should be designed to evaluate the long-term effects
of LT4 therapy on metabolic and cardiovascular risks
in SCH individuals indicating that screening and
treatment of mild thyroid hypofunction may be
warranted. Overall, despite the evidence of the
reduced CVD risk following levothyroxine therapy
in SCH, there is no consensus on the risks, benefits
and clinical importance of treatment for individuals
having TSH less than 10 mU/l, especially regarding
metabolic abnormalities, this heterogeneity in the
reports may be partly due to including different
levels of TSH [118].
THYROID AUTOIMMUNITY AND
METABOLIC SYNDROME
The role of thyroid autoimmunity in insulin resis-
tance and MetS is not well defined. Several studies
report female dominancy in MetS prevalence, simi-
lar to that reported for autoimmune thyroid disease
(AITD) [119]. Moreover, higher TSH and IL-6
Volume 26  Number 5  October 2019
 Thyroid disease and the metabolic syndrome Mehran et al.

Table 3. Studies on the association between subclinical hypothyroidism and metabolic syndrome
Reference Country Sample size Study design Mean age Major findings

de Jesus Garduno-Garcia
et al. [30]
Erdogan et al. [91]
Liu et al. [93 ]
&
Mexico 3148 Population-based, 42.3  10 SCH is not associated with an
cross-sectional increased risk for the
metabolic syndrome
Turkey 100 overt Case–control, 42.3  14.1 Metabolic syndrome is
hypothyroid patients, cross-sectional increased in patients with
100 SCH and hypothyroidism, therefore
200 controls hypothyroidism should be
considered in newly
diagnosed metabolic
syndrome patients
Taiwan 22 324 Population-based, 48.1  12.1 The prevalence of MetS was

cross-sectional higher in SCH than normal

group
Wang et al. [25] Taiwan 9095 Routine Health 51  11 No association between TSH
Investigation, and MetS, no difference in
cross-sectional MetS prevalence
Kota et al. [92] India 100 cases Case–control, 47.3  4.8 There was significant
and 50 control cross-sectional association between SH and
MetS
Heima et al. [14] Amsterdam 1167 Population-based, 75.4  6.5 Individuals with serum TSH
cross-sectional higher than 2.28 mU/l had
significantly increased risk of
metabolic syndrome
compared with individuals
with serum TSH lower than
1.04 mU/l (OR ¼ 1.68)
Nakajima et al. [90] Japan 11 498 Population-based, 48  9 Prevalence of MetS was
cross-sectional significantly higher in patients
with SCH than in euthyroid
individuals among women
Pesic et al. [94] Serbia 60 SCH Case–control, 52.0  8.7 No significant higher presence
and 60 controls cross-sectional of MetS in SCH patients in
comparison with euthyroid
respondents. hypertension
and decreased HDL
cholesterol was significantly
higher in SH patients as
compared with the control
group
Mehran et al. [89 ] Iran 5422 Population-based, 40.3  14.4 Overt hypothyroidism and
&&

cross-sectional subclinical hypothyroidism

especially in the elderly could
be associated with MetS.
Hyperthyroidism may induce
hyperglycemia
Chang et al. [95 ] Taiwan 66 822 Population-based, 41  10 Patients with metabolic
&&

cohort syndrome were at a 21%

excess risk of developing
subclinical hypothyroidism

MetS, metabolic syndrome; OR, odds ratio; SCH, subclinical hypothyroidism; TSH, thyroid stimulating hormone.

concentrations have been detected in both MetS
and AITD [120,121], suggesting the possible cross-
link between AITD and MetS. Data regarding car-
diovascular and metabolic risk in Hashimoto’s
thyroiditis are inconsistent. Waring et al. [67]
reported an increased MetS prevalence in Hashimo-
to’s thyroiditis, whereas some other studies found
no association between the presence of thyroid anti-
bodies and coronary heart disease [122,123]. A study
conducted on 9082 euthyroid Chinese adults
reported positive associations between AITD and
hemoglobin A1C, HOMA-IR, obesity, central obe-
sity, hyperlipidemia and MetS, especially in women
&&
[124 ]. Another study on euthyroid postmeno-
pausal women showed no difference in the preva-
lence of MetS between the thyroid peroxidase
antibody (TPOAb)-positive and negative groups
[120] while obese subclinical hypothyroid women

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Thyroid
with Hashimoto’s thyroiditis had a higher preva-
lence of MetS [120], in contrast to the report on
obese individuals which did not support the role of
TPOAb in the development of MetS [9]. In a recent
&
study of 5608 nonobese euthyroid individuals [93 ],
TPOAb was associated with HOMA-IR and hsCRP
levels independent of thyroid function, suggesting
insulin resistance, chronic inflammation and mild
deviation of thyroid hormones as links between
thyroid autoimmunity and metabolic abnormalities
in the nonobese population. Further clinical trials
are needed to evaluate whether levothyroxine treat-
ment could be beneficial in reducing the risk of CVD
or Mets for TPOAb positive individuals even
with euthyroidism.
HYPERTHYROIDISM AND METABOLIC
SYNDROME
Although insulin resistance is a common finding in
hyperthyroidism, MetS is less likely to occur in hyper-
thyroidism, as the hyperthyroid state is associated
with the catabolic effects of excess thyroid hormones
which may affect components of MetS such as body
weight and lipid profile; however, the dysmetabolic
state of hyperglycemia was observed in subclinical
forms of hyperthyroidism; many studies report the
presence of insulin resistance in hyperthyroidism
even its subclinical form. Maratou et al. [96] suggested
the presence of insulin resistance in both fasting and
postglucose states in line with the results of Yavuz
et al. [125,126] reporting lower insulin sensitivity in a
group with subclinical hyperthyroidism.
Thyroid hormones may exert both insulin ago-
nistic (muscles) or antagonistic (liver) actions in
different organs and thyroid hormone excess (or
even deficit) may break this balance and lead to
glucose intolerance mainly following hepatic insu-
lin resistance due to increased glucose hepatic out-
put via enhanced rates of gluconeogenesis and
glycogenolysis. Significantly, recent studies have
shown that even subtle decreases in levels of thyroid
hormones within the physiological range negatively
correlate with the insulin resistance index [127].
CONCLUSION
The review would suggest that individuals with thy-
roid hypofunction, even within low normal ranges are
already are at risk of various metabolic abnormalities;
however, the risk of MetS remains a controversial
issue. The interrelation between TSH, FT3, FT4 and
metabolic parameters is complex and might be
affected by age, sex, BMI, insulin resistance, smoking,
alcohol consumption, iodine intake and inflamma-
tory markers. As the distribution of these factors differs
262 www.co-endocrinology.com
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greatly for different populations, the same conclusion
cannot be reached for general populations. Also indi-
rect methods used for estimating insulin resistance
and BMI in most studies might not reflect fat mass
distribution and could lead to misinterpretation.
Screening and treatment of mild thyroid hypofunc-
tion may be warranted due to its adverse metabolic
and cardiovascular effects, considering the risk of
potential adverse effects of replacement therapy, such
as atrial fibrillation and osteoporosis.
The hyperthyroid state may be associated only
with insulin resistance and dysglycemia. AITD may
be a potential risk factor for metabolic abnormali-
ties, even in those with low normal TSH ranges.
Much remains to be learned about the issue
significance, before we can come to a practical con-
clusions as to whether or not thyroid hormone
treatment would be beneficial in individuals with
SCH or low normal thyroid function. Large popula-
tion-based cohort studies with longer follow-up
periods are needed to determine the significance
of early detection of thyroid dysfunction, especially
in subclinical forms and long-term associations with
MetS in different age, sex and BMI groups.
Acknowledgements
We would like to acknowledge Ms Niloofar Shiva for
critical editing of English grammar and syntax of the
article.
Financial support and sponsorship
The current research received no specific grant from any
funding agency.
Conflicts of interest
There are no conflicts of interest.
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