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421
PRACE ORYGINALNE/ORIGINAL PAPERS
Endokrynologia Polska/Polish Journal of Endocrinology
Tom/Volume 62; Numer/Number 5/2011
ISSN 0423–104X
Effects of thyroid autoimmunity on abdominal obesity
and hyperlipidaemia
Wpływ chorób autoimmunologicznych tarczycy na rozwój otyłości brzusznej
i hiperlipidemii
Gonca Tamer1, Meral Mert2, Ismet Tamer3, Banu Mesci4, Damla Kılıc4, Safiye Arık4
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Göztepe Training and Research Hospital,
Istanbul, Turkey
2Division of Endocrinology and Metabolism, Department of Internal Medicine, Okmeydani Training and Research Hospital,
Istanbul, Turkey
3Department of Family Medicine, Kartal Training and Research Hospital, Istanbul, Turkey
4Department of Internal Medicine, Göztepe Training and Research Hospital, Istanbul, Turkey
Abstract
Background: Thyroid autoimmunity has been suggested as a risk factor for atherosclerosis independent of thyroid function in several
studies. The aim of this study was to investigate whether thyroid autoimmunity had any effect on hyperlipidaemia, obesity and abdominal
obesity independent of thyroid function.
Material and methods: 184 premenopausal female patients with Hashimoto’s thyroiditis (HT) and 150 healthy premenopausal female
volunteers as control group (CG) were included in the study. According to thyroid function status, the patients were divided into three
subgroups: overt hypothyroid patients (ohp), subclinical hypothyroid patients (shp) and euthyroid patients (ep). Body mass index (BMI),
waist to hip ratios, waist circumference (WC), and serum lipid levels of all the participants were determined. These parameters of ep were
compared with those of ohp, shp and CG. Relationships among thyroid stimulating hormone (TSH), thyroid autoantibodies and lipid
levels were investigated.
Results: There were no significant differences between serum total cholesterol and low density lipoprotein cholesterol (LDL-C) levels of ohp
and ep with HT (P = 0.18, P = 0.07 respectively) and LDL-C levels of ep were higher than those of CG (P = 0.03, P = 0.042, respectively).
Although TSH levels did not correlate with serum lipid levels, levels of anti-thyroid peroxidase antibody correlated with triglyceride levels
and WCs (r = 0.158; P = 0.013, r = 0.128; P = 0.048 respectively) and negatively correlated with high density lipoprotein cholesterol (HDL-C)
levels (r = –0.137; P = 0.031). Levels of anti-thyroglobulin antibody also correlated with triglyceride and nonHDL-C levels (r = 0.208;
P = 0.007, r = 0.158; P = 0.043 respectively).
Conclusion: Thyroid autoimmunity may have some effects on hyperlipidaemia and abdominal obesity independent of thyroid function.
(Pol J Endocrinol 2011; 62 (5): 421–428)
Key words: autoimmune thyroiditis, atherosclerosis, hyperlipidaemia, abdominal obesity, LDL-C
Streszczenie
Wstęp: Wyniki badań wskazują, że choroby autoimmunologiczne tarczycy są czynnikiem ryzyka miażdżycy, bez względu na czynność
tego narządu. Celem badania było ustalenie, czy obecność chorób autoimmunologicznch tarczycy niezależnie od jej funkcji wpływa na
rozwój hiperlipidemii, otyłości i otyłości brzusznej.
Materiał i metody: Do badania włączono 184 kobiet przed menopauzą z zapaleniem tarczycy typu Hashimoto (HT) i 150 zdrowych
ochotniczek przed menopauzą, które stanowiły grupę kontrolną (CG). Chore podzielono na 3 podgrupy w zależności od stanu czynno-
ściowego tarczycy: osoby z jawną niedoczynnością tarczycy (ohp), z bezobjawową niewydolnością tarczycy (shp) i osoby z eutyreozą (ep).
U wszystkich uczestniczek badania określono wskaźnik masy ciała (BMI), wskaźnik talia/biodra, obwód talii i stężenia lipidów w surowicy.
Powyższe parametry porównano między grupą ep i pozostałymi grupami (ohp, shp, CG). Zbadano zależności między stężeniem TSH,
przeciwciał przeciwtarczycowych i stężeniami lipidów.
Wyniki: Nie stwierdzono istotnych różnic między stężeniami cholesterolu całkowitego i cholesterolu frakcji LDL między grupami ohp
i ep (odpowiednio p = 0,18 i p = 0,07). Stężenia cholesterolu frakcji LDL w grupie ep były wyższe niż w grupie CG (odpowiednio p = 0,03
i p = 0,042). Stężenia TSH nie korelowały ze stężeniami lipidów w surowicy, jednak stwierdzono prostą zależność między stężeniami
przeciwciał przeciw peroksydazie tarczycowej i stężeniami triglicerydów oraz obwodem talii (odpowiednio r = 0,158; p = 0,013, r = 0,128;
p = 0,048) i odwrotną zależność między cholesterolem frakcji HDL (r = –0,137; p = 0,031). Stężenia przeciwciał przeciw tyreoglobulinie
korelowały ze stężeniami triglicerydów i cholesterolu nie-HDL (odpowiednio r = 0,208; p = 0,007, r = 0,158; p = 0,043).
Wnioski: Choroby autoimmunologiczne tarczycy mogą wpływać na rozwój hiperlipidemii i otyłości brzusznej niezależnie od stanu
czynnościowego tego narządu. (Endokrynol Pol 2011; 62 (5): 421–428)
Słowa kluczowe: autoimmunologiczne zapalenie tarczycy, miażdżyca, hiperlipidemia, otyłość brzuszna, cholesterol frakcji LDL
Gonca Tamer, Division of Endocrinology and Metabolism, Department of Internal Medicine, Göztepe Training and Research Hospital,
Istanbul, Tellikavak sok. No:8, Topbas sitesi, A blok, D:24, Erenkoy, Istanbul 34738, Turkey, tel: +90 532 332 09 29, fax: +90 216 414 19 06,
(Attn: Dr I.Tamer), e-mail: hgtamer@yahoo.com
422
PRACE ORYGINALNE
Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia Gonca Tamer et al.
Introduction
Hypothyroidism is a known common risk factor for
obesity and hyperlipidaemia. Hashimoto’s thyroiditis
(HT) is the commonest cause of hypothyroidism [1–4].
But it is not clear if thyroid autoimmunity is a risk fac-
tor for obesity and hyperlipidaemia independent of
thyroid function.
The involvement of thyroid autoimmunity in at-
herosclerosis as a risk factor for coronary heart disease
independent of thyroid function has been suggested in
some previous studies. Increased serum levels of circu-
lating thyroid and/or other autoantibodies have often
been observed in the atherosclerotic process [5–10].
In 1991, Volpe suggested that HT is predominantly
a disorder of cell-mediated immunity that is manifested
by a genetic defect in the suppressor T-cell function [11].
According to this hypothesis, in HT, helper (CD4) T cells
are not suppressed because of the defective suppressor
T cells, and therefore are able to produce various cyto-
kines such as interferon (IFN)-g, interleukin (IL)-2 and
tumour necrosis factor (TNF)-a [12].
Recently, a study performed in mice determined that
(IFN)-g regulates fat inflammation and TNF-a promotes
lipogenesis and induces lipolysis [13].
There are a few studies suggesting that thyroid auto-
immunity is a risk factor for atherosclerosis independent
of thyroid function. However in HT, T helper cells may
not be suppressed and can produce some cytokines
such as IFN-g and TNF-a as suggested by Volpe [11].
These cytokines might cause weight gain, lipogenesis
and lipolysis in humans as in mice, as suggested by
Sultan [13].
Combining Volpe’s hypothesis with Sultan’s find-
ing, it is possible that thyroid autoimmunity might
cause weight gain and hyperlipidaemia independent
of thyroid function.
In this study, we hypothesised that thyroid auto-
immunity may have some effects on hyperlipidaemia,
obesity and abdominal obesity independent of thyroid
function.
With this aim, we investigated body mass index
(BMI), waist circumference (WC), waist to hip ratio
(WHR), rates of obesity and abdominal obesity and total
cholesterol (TC), high density lipoprotein cholesterol
(HDL-C), triglyceride (TG), low density lipoprotein
cholesterol (LDL-C), and non-high density lipoprotein
cholesterol (non-HDL-C) levels of euthyroid patients
(ep) with Hashimoto’s thyroiditis, and compared them
with those of overt hypothyroid patients (ohp), subclini-
cal hypothyroid patients (shp) and healthy subjects. We
also examined if each one of those lipid parameters,
BMIs, WCs and WHRs correlated with serum thyroid
stimulating hormone (TSH), autoantibodies against
thyroglobulin (TgAb) and thyroid peroxidase (TPOAb)
concentrations separately in all the patients with HT.
Material and methods
The study included 184 premenopausal female pa-
tients with newly diagnosed and untreated HT and
150 healthy premenopausal female volunteers as the
control group (CG). All CG subjects were matched for
age with HT patients (Table I). This study was approved
by our institutional ethics committee (approval date and
number: 21.02.2008, 44/E) and the study subjects have
therefore been recruited to the study in accordance with
ethical standards announced in the 1964 Declaration of
Helsinki. All the subjects in this study gave informed
consent prior to their inclusion.
Lymphocytic infiltration of the thyroid gland is
present up to 40% of healthy women [3, 14] and it is
known that loss of oestrogen at the menopause causes
an increase in serum LDL-C levels and weight gain [15].
Therefore, the present study was designed to include
premenopausal women. Patients with liver disorders,
renal disorders, congestive heart failure, diabetes mel-
litus, pregnant women, patients on oral contraceptive
pills, fibrates and/or statins, steroids, thiazides, beta
blockers, or with other medications that might alter or
influence body weight, serum lipid levels or thyroid
functions were excluded from the study. A diagnosis
of HT was made in the presence of elevated antithy-
roid peroxidase and antithyroglobulin antibodies and
ultrasound patterns suggestive of HT [2].
HT patients were classfied into three subgroups
according to their thyroid function status. Overt hy-
pothyroid patients (ohp, n = 51; 27.71%) were those
with serum TSH > 10 uIU/mL (reference interval was
0.27–4.2 uIU/mL) and free T4 < 0.93 ng/dL (reference
interval was 0.93–1.7 ng/dL).
Subclinical hypothyroid patients (shp, n = 49;
26.63%) were those with normal serum free T4 and free
T3 levels but with high serum TSH levels.
Euthyroid patients (ep, n = 84; 54.34%) were those
with HT but normal free T4 and TSH levels [3, 14].
BMI was calculated as body weight (kg) divided by
height (m) squared [16] and obesity was defined as BMI
of 30 or more (kg/m2) [17, 18]. Waist and hip circumfe-
rences of all the patients were measured and waist to
hip ratios (WHRs) were calculated.
Waist circumferences were measured at the plane
between anterior superior iliac spines and lower costal
margins at the narrowest part of the waistline while
patients were standing during slight expiration [16–18].
For women, WC > 88 cm was accepted as abdominal
obesity according to WC [19]. Hip circumferences
were measured horizontally over the furthest points
423
Endokrynologia Polska/Polish Journal of Endocrinology 2011; 62 (5)
PRACE ORYGINALNE
of trochanters while standing with 20–30 cm distance
between feet. A measure of WHR > 0.85 was accepted
as abdominal obesity for women [17, 19].
Blood samples were taken following 12 hours of
fasting, and immediately centrifuged (2,500 rpm) and
the sera were separated. TC, HDL-C and TG levels
were determined by enzymatic methods and LDL-C
levels were determined using the Friedewald formula
[20]. Those patients whose TG levels were higher than
400 mg/dL were excluded from the study as they might
have limitation of the calculation of LDL-C levels [20].
Serum autoantibodies against thyroglobulin (TgAb)
and thyroid peroxidase (TPOAb), TSH, free T3 and free
T4 levels were measured by electrochemiluminescence
immunoassay ECLIA (Modular Analytics E170; Roche
Diagnostics). The normal ranges were 0–34 IU/mL for
TPOAb levels and 0–115 IU/mL for TgAb levels.
Statistical analysis
All statistical analyses were made using SPSS 13.0.
Normality of the distribution of variables was tested
by Shapiro-Wilk and Kolmogorov-Smirnov tests. Waist
circumference, total cholesterol, non-HDL cholesterol,
HDL-C and LDL-C were compared by independent
samples t — test in all hypothyroidism patients and
control group, in ohp and control group, in shp and
control group, and in ep and control group. The same
parameters were compared by one-way analysis of va-
riance (ANOVA) for more than two categories. TG, BMI,
WHR, TSH, TPOAb and TgAb were compared by the
Wilcoxon–Mann–Whitney U test in all hypothyroidism
patients and control group, in ohp and control group,
in shp and control group, and in ep and control group.
The same parameters were compared by Kruskal Wallis
test for groups with more than two levels. A factorial
logistic regression was used when we had two or more
categorical independent variables but a dichotomous
dependent variable. Pearson’s correlation coefficients
among TSH, TPOAb, Tg Ab, BMI, WC, WHR, lipid para-
meters were determined using regression analyses. Data
was reported as means ± SD. Significant differences
were assumed for p < 0.05.
Results
Characteristics of all subjects are shown in Tables I–IV.
Serum TC, LDL-C, TG and non-HDL-C levels of all
the patients with HT were significantly higher than
those of CG (P = 0.01, P = 0.002, P = 0.001, P < 0.0001,
respectively) (Table I). Means of BMI and WC, rates of
obesity and abdominal obesity according to WC, serum
TC, LDL-C, TG and non-HDL-C levels of ohp were sig-
nificantly higher than those of CG (P = 0.026, P = 0.01,
P = 0.013, P = 0.029, P = 0.01, P = 0.001, P = 0.001,
P = 0.001, respectively) (Table II). We interestingly
Table I. Comparison of the characteristics of patients with Hashimoto’s thyroiditis [HT] and the control group
Tabela I. Porównanie parametrów między chorymi na zapalenie tarczycy typu Hashimoto (HT) i kobietami z grupy kontrolnej
Patients with HT
(n = 184)
Control group
(n = 150)
p
Age 35.48 ± 7.92 35.71 ± 7.85 NS
TSH [uIU/mL] 15.51 ± 44.88 1.69 ± 0.93 0.0005
TPOAb [IU/mL] 292.47 ± 361.7 11.7 ± 33.6 0.0005
TgAb [IU/mL] 461.22 ± 788.46 21.95 ± 43.38 0.0005
BMI 28.30 ± 6.21 27.98 ± 7.09 NS
Rate of obesity 60 [34.3%] 44 [29.7%] NS
WC [cm] 88.89 ± 3.14 86.27 ± 14.80 NS
Rate of abdominal obesity according to WC 88 [53.3%] 66 [47.1%] NS
WHR [cm] 0.809 ± 0.06 0.801 ± 0.7 NS
Rate of abdominal obesity according to WHR 47 [28.7%] 40 [28.6%] NS
TC [mg/dL] 197.12 ± 38.96 184.79 ± 36.23 0.01
LDL-C [mg/dL] 129.55 ± 30.63 116.39 ± 28.57 0.002
HDL-C [mg/dL] 54.84 ± 13.09 56.19 ± 14.88 NS
TG [mg/dL] 118.20 ± 66.85 97.92 ± 58.95 0.001
non-HDL-C [mg/dL] 142.28 ± 36.40 128.60 ± 3413 < 0.0001
BMI — body mass index; WC — waist circumference; WHR — waist-to-hip ratio; TC — total cholesterol; LDL-C — low-density lipoprotein cholesterol;
HDL-C — high-density lipoprotein cholesterol; TG — triglyceride; non-HDL-C — non-high-density lipoprotein cholesterol; NS — non-significant
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Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia Gonca Tamer et al.
Table II. Comparison of the characteristics of overt hypothyroid patients [ohp] with Hashimoto’s thyroiditis (HT)
and control group
Tabela II. Porównanie parametrów między grupą chorych na zapalenie tarczycy typu Hashimoto (HT) z jawną niedoczynnością
tarczycy (ohp) i grupą kontrolną
ohp with HT
(n = 51)
Control Group
(n = 150)
p
Age 35.75 ± 7.75 35.71 ± 7.85 NS
TSH [uIU/mL] 31.83 ± 31.47 1.69 ± 0.93 0.0005
TPOAb [IU/mL] 421.19 ± 551.99 11.70 ± 33.6 0.0005
TgAb [IU/mL] 574.48 ± 1016.6 21.95 ± 43.38 0.0005
BMI 30.34 ± 6.69 27.98 ± 7.09 0.026
Rate of obesity 26 [52%] 44 [29.7%] 0.013
WC [cm] 93.17 ± 13.35 86.27 ± 14.80 0.010
Rate of abdominal obesity according to WC 28 [68.3%] 66 [47.1%] 0.029
WHR [cm] 0.816 ± 0.72 0.801 ± 0.7 NS
Rate of abdominal obesity according to WHR 10 [24.4%] 40 [28.6%] NS
TC [mg/dL] 202.53 ± 41.41 184.79 ± 36.23 0.01
LDL-C [mg/dL] 136.14 ± 33.55 116.39 ± 28.57 0.001
HDL-C [mg/dL] 51.52 ± 11.86 56.19 ± 14.88 NS
TG [mg/dL] 131.25 ± 73.66 97.92 ± 58.95 0.001
non-HDL-C [mg/dL] 151.31 ± 39.24 128.60 ± 3413 0.001
Table III. Comparison of the characteristics of subclinical hypothyroid patients [shp] with Hashimoto’s thyroiditis (HT)
and control group
Tabela III. Porównanie parametrów między grupą chorych na zapalenie tarczycy typu Hashimoto (HT) z bezobjawową
niedoczynnością tarczycy (shp) i grupą kontrolną
shp with HT
(n = 49)
Control group
(n = 150)
p
Age 35.94 ± 8.75 35.71 ± 7.85 NS
TSH [uIU/mL] 21.04 ± 77.66 1.69 ± 0.93 0.0005
TPOAb [IU/mL] 296.45 ± 312.92 11.7 ± 33.6 0.0005
TgAb [IU/mL] 603.36 ± 974.77 21.95 ± 43.38 0.0005
BMI 26.81 ± 5.81 27.98 ± 7.09 NS
Rate of obesity 12 [26.1%] 44 [29.7%] NS
WC [cm] 86.27 ± 14.59 86.27 ± 14.80 NS
Rate of abdominal obesity according to WC 21 [47.7%] 66 [47.1%] NS
WHR [cm] 0.802 ± 0.64 0.801 ± 0.7 NS
Rate of abdominal obesity according to WHR 10 [23.3%] 40 [28.6%] NS
TC [mg/dL] 196.39 ± 41.03 184.79 ± 36.23 NS
LDL-C [mg/dL] 128.24 ± 33.02 116.39 ± 28.57 0.031
HDL-C [mg/dL] 54.02 ± 13.37 56.19 ± 14.88 NS
TG [mg/dL] 112.11 ± 62.72 97.92 ± 58.95 NS
non-HDL-C [mg/dL] 142.37 ± 40.07 128.60 ± 3413 NS
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Endokrynologia Polska/Polish Journal of Endocrinology 2011; 62 (5)
PRACE ORYGINALNE
Table V. Comparison of the characteristics of overt hypothyroid patients [ohp], subclinical hypothyroid patients (shp)
and euthyroid patients (ep)
Tabela V. Por ównanie parametrów między grupami chorych na zapalenie tarczycy typu Hashimoto (HT) z jawną niewydolnością
tarczycy (ohp), bezobjawową niewydolnością tarczycy (shp) i eutyreozą (ep)
ohp (n = 51) shp (n = 49) ep (n = 84) p
Age 35.75 ± 7.75 35.94 ± 8.75 35.5 ± 7.58 NS
TSH [uIU/mL] 31.83 ± 31.47 21.044 ± 77.66 2.38 ± 1.05 0.0005
TPOAb [IU/mL] 421.19 ± 551.99 296.45 ± 312.92 212.77 ± 176.78 0.001
TgAb [IU/mL] 574.48 ± 1016.61 603.36 ± 974.77 305.14 ± 378.74 NS
BMI 30.34 ± 6.69 26.81 ± 5.81 27.88 ± 7.09 0.03
Rate of obesity 26 (52%) 12 (26.1%) 22 (27.8%) NS
WC [cm] 93.17 ± 13.35 86.27 ± 14.59 88.13 ± 11.77 0.04
Rate of abdominal obesity according to WC 28 (68.3%) 21 (47.7%) 39 (48.8%) NS
WHR [cm] 0.816 ± 0.72 0.802 ± 0.64 0.81 ± 0.58 NS
Rate of abdominal obesity according to WHR 10 (24.4%) 10 (23.3%) 27 (33.8%) NS
TC [mg/dL] 202.53 ± 41.41 196.39 ± 41.03 194.17 ± 36.26 NS
LDL-C [mg/dL] 136.14 ± 33.55 128.24 ± 33.02 126.27 ± 26.92 0.01
HDL-C [mg/dL] 51.52 ± 11.86 54.02 ± 13.37 57.56 ± 13.2 NS
TG [mg/dL] 131.25 ± 73.66 112.11 ± 62.72 113.5 ± 64.31 0.01
non-HDL-C [mg/dL] 151.31 ± 39.24 142.37 ± 40.07 136.61 ± 31.39 NS
Table IV. Comparison of the characteristics of euthyroid patients (ep) with Hashimoto’s thyroiditis (HT) and control group
Tabela IV. Porównanie parametrów między grupą chorych na zapalenie tarczycy typu Hashimoto (HT) z eutyreozą (ep)
i grupą kontrolną
ep with HT
(n = 84)
Control group
(n = 150)
p
Age 35.05 ± 7.58 35.71 ± 7.85 NS
TSH [uIU/mL] 2.38 ± 1.05 1.69 ± 0.93 0.0005
TPOAb [IU/mL] 212.77 ± 176.78 11.70 ± 33.60 0.0005
TgAb [IU/mL] 305.14 ± 378.74 21.95 ± 43.38 0.0005
BMI 27.88 ± 7.09 27.98 ± 7.09 NS
Rate of obesity 22 [27.8%] 44 [29.7%] NS
WC [cm] 88.13 ± 11.77 86.27 ± 14.80 NS
Rate of abdominal obesity according to WC 39 [48.8%] 66 [47.1%] NS
WHR [cm] 0.81 ± 0.58 0.801 ± 0.7 NS
Rate of abdominal obesity according to WHR 27 [33.8%] 40 [28.6%] NS
TC [mg/dL] 194.17 ± 36.26 184.79 ± 36.23 NS
LDL-C [mg/dL] 126.27 ± 26.92 116.39 ± 28.57 0.0042
HDL-C [mg/dL] 57.56 ± 13.2 56.19 ± 14.88 NS
TG [mg/dL] 113.5 ± 64.31 97.92 ± 58.95 NS
non-HDL-C [mg/dL] 136.61 ± 31.39 128.60 ± 3413 NS
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Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia Gonca Tamer et al.
determined that LDL-C levels of ep were significantly
higher than those of CG (P = 0.042) (Table IV). LDL
levels of shp were also significantly higher than those
of CG (P = 0.031) (Table III). Contrary to expectations,
TSH levels did not correlate with LDL-C levels in all
the patients with HT (r = 0.045; P = 0.551). Total cho-
lesterol, TG, nonHDL-C, and HDL-C levels did not
correlate with TSH levels either (r = 0.039; P = 0.606,
r = 0.063; P = 0.399, r = 0.044; P = 0.554, r = –0.008;
P = 0.914 respectively). We surprisingly observed that
serum TPOAb concentrations correlated with TG levels
and WCs (r = 0.158; P = 0.013, r = 0.128; P = 0.048 res-
pectively) and negatively correlated with HDL-C levels
in all the patients with HT (r = –0.137; P = 0.031). Se-
rum TgAb concentrations also correlated with TG and
nonHDL-C levels in all the patients with HT (r = 0.208;
P = 0.007, r = 0.158; P = 0.043 respectively). TSH levels
correlated with TgAb levels (r = 0.187; P = 0.015), but
did not correlate with TPOAb levels in all the patients
with HT (r = 0.081; P = 0.280).
Serum TSH and TPOAb levels of ohp were signifi-
cantly higher than those of ep (P = 0.0005, P = 0.0005,
respectively), and those of shp (P = 0.0005, P = 0.044,
respectively). However, there was no significant diffe-
rence among TgAb levels of ohp, shp and ep (P = 0.19).
Body mass index, WC and rate of obesity of ohp
were higher than those of shp (P = 0.006, P = 0.023,
P = 0.009, respectively). Between ohp and shp, there
was no significant difference concerning serum TC,
LDL-C, HDL-C, TG and non-HDL-C levels, and rates
of abdominal obesity according to WC and WHR.
(P = 0.40, P = 0.27, P = 0.37, P = 0.11, and P = 0.25,
P = 0.054, P = 0.903, respectively). Body mass index
and WC and rates of obesity and abdominal obesity
according to WC of ohp were significantly higher
than ep (P = 0.037, P = 0.035, P = 0.006, P = 0.039,
respectively). Serum TG and non-HDL levels of ohp
were also higher than those of ep (P = 0.04, P = 0.02,
respectively) and serum HDL-C levels of ep with HT
were higher than those of ohp (P = 0.02). But there
was no significant difference between serum TC
and LDL-C levels of ohp and ep with HT (P = 0.18,
P = 0.07 respectively).
Discussion
Unlike most previous studies, in the present study
serum LDL-C levels of ep with HT were determined
to be higher than those of healthy subjects and there
was no significant difference between serum TC and
LDL-C levels of ohp and of ep with HT. Not only ohp
but also all the patients with HT had higher serum
TC, LDL-C, TG, and non HDL-C levels compared to
healthy subjects. There were no correlations between
TSH and LDL-C levels or between TSH and other lipid
parameters in all the patients with HT. However, TPOAb
concentrations negatively correlated with HDL-C and
positively correlated with TG levels and WCs in all the
patients with HT. Serum TgAb concentrations also cor-
related with TG and nonHDL-C levels.
These findings suggest that thyroid autoimmunity
may be associated with hyperlipidaemia independent
of thyroid function, as suggested in the old studies by
the Bastenie et al. [8–10]. Overt hypothyroidism (OH)
is not only one of the causes of obesity but also a risk
factor for atherosclerotic cardiovascular disease and
hyperlipidaemia as well. Moreover, OH has been found
to be associated with insulin resistance [21].
It is known that serum TC, LDL-C, TG, free fatty
acid (FFA) levels and BMIs of ohp are higher than those
of healthy subjects [3, 21–25]. Elevated levels of FFAs
stimulate insulin secretion, placing a further burden on
genetically compromised and stressed -cell function in
individuals susceptible to type 2 diabetes. Furthermore,
elevated FFAs have been reported to impair early insulin
secretion, a characteristic B-cell abnormality in type 2
diabetes. In addition, increased flux of FFA to the liver
increases hepatic gluconeogenesis and hepatic glucose
output, adding to already existing abnormalities in
hepatic glucose metabolism in type 2 diabetes [1]. Re-
cently, it has been demonstrated that insulin resistance
may modify the relationship between lipids and thyroid
function and the association between elevated TSH and
LDL-C levels varies depending on the degree of insulin
sensitivity [26–31].
In the present study, BMI, WC, rates of obesity and
abdominal obesity according to WC, serum TC, TG,
LDL-C and non-HDL-C levels of ohp with HT were
higher than those of healthy subjects, but there was no
significant difference between HDL-C levels of ohp and
those of healthy people.
Many studies have investigated the relationship
between thyroid function and serum lipid levels and
determined various findings. A large cross-sectional
survey of 3,410 elderly subjects in Maryland noted
significantly elevated LDL-C levels in subjects with
subclinical hypothyroidism, but no increased frequency
of diagnosed atherosclerotic disease could be found in
the entire cohort of shp [32]. McDermott et al. found
that overt hypothyroidism and also subclinical hypo-
thyroidism (SH) lead to increased blood pressure and
triglyceride levels and decreased HDL-C levels [33]. Ca-
naris determined that shp had higher serum cholesterol
levels than ep [34], and in another study it was observed
that LDL-C levels were higher and HDL-C levels were
lower in shp than those in healthy subjects [35].
A report from Rotterdam noted that shp actually
had lower TC levels than controls, but manifested inc-
427
Endokrynologia Polska/Polish Journal of Endocrinology 2011; 62 (5)
PRACE ORYGINALNE
reased atherosclerotic cardiovascular disease [36], This
finding suggests that some other factors contribute to
the increased risk of atherosclerosis independent of se-
rum TC levels [36]. In another large study, no difference
could be determined between serum cholesterol levels
of shp and those of healty subjects [37]. Uzunlulu et
al. did not observe any difference between serum TG,
HDL-C levels of 36 shp and of 190 healthy subjects [38].
Shantha et al. also could not determine any difference
among serum TC, TG, HDL-C levels of 92 shp, 31 ohp
and 406 healthy subjects [39].
In the present study, serum LDL-C levels of shp
and ep were higher than healthy subjects. However,
there was no significant difference between serum TC,
TG, HDL-C and non-HDL-C levels of shp with HT and
healthy people, and also between those of ep with HT
and healthy subjects.
Contrary to the studies which determined the asso-
ciation between high TSH levels and hyperlipidaemia,
another study has identified subclinical hypothyroidism
as an independent risk factor for aortic atherosclerosis
and myocardial infarction in elderly women [36].
In the present study, it was determined that TSH
levels suprisingly did not correlate with LDL-C levels
or other lipid parameters.
Based on the data, the association between overt
hypothyroidism and cardiovascular disease or between
subclinical hypothyroidism and cardiovascular disease
may not be entirely explained by dyslipidaemia alone.
The involvement of the immune system in atheroscle-
rosis is mainly suggested by the presence of activated
T cells within the atherosclerotic lesions and of circula-
ting autoantibodies to plaque components. Two studies
focused on the involvement of two major autoantigenic
determinants in the atherogenic process, namely, the
heat shock protein and oxi LDL-C [5, 6]. According to
this view, after early activation of the immune system,
the progression of the atherosclerotic lesions would be
enhanced by focal secretion of cytokine and growth
factor networks. In the framework of the above scena-
rio, the increased serum levels of circulating thyroid
and/or other autoantibodies are often observed in the
elderly and reflect an ongoing autoimmune activation
involved in the atherosclerotic process leading to inc-
reased risk of coronary heart disease. No direct support
to this hypothesis has been provided. However, in
one of the few studies addressing this question more
directly, a significant correlation was found in humans
between atherosclerotic lesions and circulating anti-hsp
65 antibodies, while in the same patients, the arterial
damage was unrelated to serum thyroid and other
autoantibodies [5, 7].
On the epidemiological basis, thyroid autoimmu-
nity as a risk factor for coronary heart disease inde-
pendent of thyroid function, as suggested by Bastenie
et al. [8–10], has not been confirmed in more recent
investigations [40].
Many studies determined that elevated serum li-
pid levels were associated with TSH elevations. In the
HUNT study, the association of hypothyroidism with
high serum lipids was linear across the entire reference
range of TSH [41]. Tagami et al. determined positive
correlation between serum TSH and lipid levels [42].
However, the Whickham study showed that elevated
serum lipid levels were not associated with TSH eleva-
tions [43] and during the follow up of the Whickham
survey, investigators found no association between
elevated serum TSH and the increased risk of ischaemic
heart disease or dyslipidaemia [44].
Complying with the Whickam study, in the pre-
sent study, TSH levels did not correlate with serum
lipid levels, BMI and WC. However, it was suprisingly
found that TPOAb concentrations correlated with TG
levels and WC and negatively correlated with HDL-C
levels and TgAb concentrations correlated with TG and
nonHDL-C levels. Besides, serum LDL-C levels of ep
with HT were found to be higher than those of healthy
subjects and there was no significant difference between
serum TC and LDL-C levels of ohp and ep with HT. It
was another notable finding in the study that there was
no significant difference between TgAb levels of ohp
and those of ep.
These findings support the idea that thyroid autoim-
munity is a risk factor for hyperlipidaemia independent
of the thyroid function.
It is not clear how thyroid autoimmunity affects obe-
sity, abdominal obesity and serum lipid levels. However,
in HT it is possible that increased IFN-g and TNF-a may
cause obesity and hyperlipidaemia without elevated
TSH levels.
In conclusion, although overt hypothyroidism has
more effect on hyperlipidaemia and obesity, thyroid
autoimmunity may have some effects on hyperlipida-
emia and abdominal obesity independent of thyroid
function. Therefore it may be beneficial to determine
the TC, LDL-C, HDL-C, TG, nonHDL-C levels and WCs
of all patients with HT, even if they are euthyroid. Furt-
her studies are needed to investigate the relationships
between thyroid autoantibodies and hyperlipidaemia
and between thyroid autoantibodies and abdominal
obesity.
Conflict of interest
The authors have disclosed that they have no signifi-
cant relationships with, or financial interests in, any
commercial company that pertains to this educational
activity.
428
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Effects of thyroid autoimmunity on abdominal obesity and hyperlipidaemia Gonca Tamer et al.
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