Key words
thyroid - thyroid-stimulating hormone - serum lipids
Introduction
Thyroid-stimulating hormone (TSH) is secreted by the pituitary gland, which regulates
the proliferation of thyroid cells, thyroid blood supply, and synthesis and
secretion of thyroid hormones. These processes maintain normal thyroid function. TSH
is the most sensitive indicator of thyroid function.
The thyroid function is closely related to the metabolism of blood lipids. The change
in blood lipids in hypothyroidism and hyperthyroidism is usually the opposite. Some
studies revealed that hypothyroidism might lead to hyperlipidemia, while
hyperthyroidism leads to a decrease in blood lipids [1]. Hypercholesterolemia is the most common lipoprotein change in
hypothyroidism. Salter et al. found that the expression of LDL receptor in liver
cells of hypothyroid rats was significantly lower than that of normal control rats,
and further studies on isolated hepatocytes showed that T3 could directly
increase the steady-state concentration of the mRNA for the LDL receptor by
25%, which indicated that thyroid hormone may stimulate the synthesis and
expression of LDL receptor in liver [2]. In
addition, with the decrease of thyroid hormone levels, sterol regulatory
element-binding protein 2 (SREBP-2) levels decline followed closely by a drop in LDL
receptor mRNA, which caused a decrease in high affinity LDL cholesterol uptake in
the liver leading to hypercholesterolemia [3]
[4]. These results suggested that
hypercholesterolemia in hypothyroidism may be due to the decrease of LDL receptor
activity. With 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) as a rate-limiting
enzyme of cholesterol synthesis, TSH could reduce the phosphorylation of HMG-CoA via
AMP-activated protein kinase (AMPK) in the liver, leading to increased HMG-CoA
reductase activity, which increases cholesterol levels in the liver [5]. TSH can also directly upregulate the
expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the liver,
thus increasing the cholesterol content in liver and serum of rats after
thyroidectomy [6].
The lipid peroxidation in patients with severe subclinical hypothyroidism was
significantly higher than in those with normal thyroid function; this phenomenon is
related to high risks of atherosclerosis [7].
Beibei et al. analyzed the correlations between serum TSH levels and serum lipids in
110 subjects with subclinical hypothyroidism and 1240 subjects with normal thyroid
function by cluster sampling inclusion, indicating TSH as a risk factor for
dyslipidemia independent of insulin resistance [8]. In a meta-analysis of a prospective cohort study, it was shown that
subclinical hyperthyroidism and hypothyroidism may be associated with increased
risks of death due to coronary heart diseases [9].
In contrast, Jiaoyue et al. found that after adjusting for age and other confounding
factors, there is no correlation between TSH level and blood lipids [10]. However, a linear dose-dependent
correlation between high TSH level in the normal range and dyslipidemia, possibly
mediated by the effect of thyroid hormones on insulin sensitivity, was revealed in a
large population-based study [11]. In patients
with normal thyroid function and newly diagnosed asymptomatic coronary heart
disease, the increased TSH level may have adverse effects on blood lipids and may
also be a risk factor for hypercholesterolemia and hypertriglyceridemia [12]. Therefore, the present study aimed to
explore the correlations between serum normal TSH levels and serum lipids.
Subjects and Methods
Subjects
A total of 2885 subjects participating in the national survey on thyroid diseases
and iodine nutrition status 2014 in Gansu Province, China were selected. After
screening by inclusion and exclusion criteria, a total of 1962 subjects
(including 1077 males and 885 females) were included in this study.
Inclusion criteria were as follows: Subjects aged ≥18 years, Han
nationality, at least 5 years of residence in the same community (village), and
normal thyroid function, were recruited in the present study.
Exclusion criteria were as follows: Patients with previous thyroid dysfunction,
whether or not treated with drugs; patients with thyroid dysfunction diagnosed
for this study; patients with hypothalamic and pituitary diseases, diabetes, and
other endocrine diseases, malignant tumors, severe liver and kidney diseases,
acute cerebrovascular diseases, hereditary hyperlipidemia; pregnant or lactating
women.
Ethical Approval
All procedures performed in studies involving human participants were in
accordance with the ethical standards of the institutional and with the 1964
Helsinki declaration and its later amendments or comparable ethical standards.
Written and oral information of the protocol was explained to them before
screening, and informed consent was obtained from each eligible participant.
Methods
Baseline information of the subjects
The baseline data with respect to demographics, education level, drinking and
smoking history, disease history, and family history of the patients were
collected. Also, the height, weight, waist circumference (WC), systolic blood
pressure (SBP), and diastolic blood pressure (DBP) were measured. The height and
weight of each subject were measured by professional medical staff; the subjects
were required to take off their shoes and wear thin clothing. Body mass index
(BMI) was calculated by dividing weight by height squared
(kg/m2). The WC was measured at the umbilical plane,
while SBP and DBP were measured using an electronic sphygmomanometer after a
10-minute rest. After fasting for 8 hours at night, 5 ml urine samples were
collected in the morning to measure the urinary iodine concentration (UIC).
Determination of serum biochemical indicators
After fasting for 8 hours at night, the venous blood samples were collected in
the morning. The fasting plasma glucose (FPG), total cholesterol (TC),
triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density
lipoprotein cholesterol (LDL-C) levels were measured using the Bs-220Automatic
Biochemical Analyzer (Mairui Biotechnology Co. Ltd, China). The reagent was
purchased from Meigao Medical Technology Co. Ltd (China).
The serum TSH levels of every subject were measured by chemiluminescence
immunoassay (Cobas 601 Analyzer, Roche diagnostics, Switzerland). The reference
range of serum TSH was 0.27–4.20 mIU/l, and the limit of
detection was 0.002 mIU/l. The intra-assay and inter-assay coefficient
of variation were 1.9–9.5% and 1.1–6.3%,
respectively. The urinary iodine concentration was determined by inductively
coupled plasma mass spectrometry (Agilent 7700x, Agilent Technologies, USA). The
intra-assay coefficients of variation were 2.3, 2.5 and 2.4%, and
inter-assay coefficients of variation were 2.7, 1.4 and 2.3%,
respectively.
Grouping of the subjects
Among the different age groups (youth: 18–44 years; middle age:
45–59 years; elderly: ≥60 years) or different gender groups, the
subjects were divided into four groups according to the quartiles of serum
normal TSH levels (0.27–4.20) mIU/l, [Q1
(0.27–1.68) mIU/l, Q2 (1.69–2.35)
mIU/l, Q3 (2.36–3.07) mIU/l, and
Q4 (3.08–4.20) mIU/l]. The effect of serum TSH
levels within the normal range on serum lipid profiles of different ages or
different gender were analyzed.
TC ≥5.2 mmol/l; TG ≥1.70 mmol/l; LDL-C
≥3.4 mmol/l; and HDL-C <1.04 mmol/l were
considered as diagnosis of dyslipidemia [13].
Statistical analysis
All data were analyzed using SPSS25.0. Measurement data of normal distribution
are expressed as mean±standard deviation (x̄±s), and the
independent sample t-test was used to compare the differences between two
groups. The data of urinary iodine concentration showed a skew distribution,
which was expressed as median (p25, p75), and nonparametric test was used to
compare the differences between groups. After adjusting for confounding factors,
an analysis of covariance (ANCOVA) was used for comparison between multiple
groups and LSD-t for the pairwise comparison. The enumeration data were
expressed as frequency and percentage. The chi-square test was used to compare
the differentiation between inter-group rates. A p-value of <0.05 was
considered statistically significant.
Results
Baseline characteristics of all subjects
A total of 1962 subjects (1077 males and 885 females) were included. The TSH
levels of females were higher than those of males (p <0.05). The BMI,
SBP, DBP, FPG, TG, and LDL-C levels were significantly higher in men than women
(p <0.05), while the HDL-C levels were lower (p <0.05).
Moreover, no significant difference was observed in age, UIC, and TC levels
between men and women ([Table 1]).
Table 1 Baseline characteristics of the subjects.
|
Variables
|
Total population
|
Males
|
Females
|
|
Cases (n)
|
1962
|
1077
|
885
|
|
Age (years)
|
40.32±14.21
|
40.54±14.17
|
40.04±14.25
|
|
BMI (kg/m2)
|
23.49±3.25
|
24.23±3.25
|
22.58±3.25*
|
|
SBP (mmHg)
|
123.74±16.56
|
125.42±14.78
|
121.68±18.30*
|
|
DBP (mmHg)
|
76.78±10.92
|
78.96±10.46
|
74.11±10.87*
|
|
FPG (mmol/l)
|
5.18±0.90
|
5.23±0.92
|
5.11±0.86*
|
|
UIC (μg/l)
|
223.40 (157.80, 309.40)
|
220.35 (157.93, 293.70)
|
229.90 (157.30, 322.60)
|
|
TC (mmol/l)
|
4.32±0.92
|
4.34±0.87
|
4.30±0.97
|
|
TG (mmol/l)
|
1.46±1.02
|
1.60±1.07
|
1.29±0.92*
|
|
HDL-C (mmol/l)
|
1.50±0.37
|
1.39±0.34
|
1.64±0.36*
|
|
LDL-C (mmol/l)
|
2.53±0.72
|
2.61±0.70
|
2.44±0.73*
|
|
TSH (mIU/l)
|
2.39±0.90
|
2.31±0.87
|
2.49±0.92*
|
|
High TG [n (%)]
|
495 (25.2)
|
331 (30.7)
|
164 (18.5)*
|
|
High TC [n (%)]
|
311 (15.9)
|
171 (15.9)
|
140 (15.8)
|
|
High LDL-C [n (%)]
|
226 (11.5)
|
137 (12.7)
|
89 (10.1)
|
|
Low HDL-C [n (%)]
|
138 (7.0)
|
117 (10.9)
|
21 (2.4)*
|
|
Dyslipidemia [n (%)]
|
759 (38.7)
|
479 (44.5)
|
280 (31.6)*
|
* p <0.05: Compared with males.
The prevalence of high TG (30.7%) and low HDL-C (10.9%) in men
was significantly higher than that in women (18.5%) and (2.4%).
There was no significant difference in the prevalence of high TC and high LDL-C
between men and women. Also, the total prevalence of dyslipidemia in men was
significantly higher than that in women (44.5 vs. 31.6%) ([Table 1]).
Comparison of serum lipids between different age groups with different serum
TSH levels
After adjusting for gender, BMI, SBP, DBP, FPG, and UIC, the TC and LDL-C levels
of Q3 group were higher than those of Q1 group (p
<0.05), and the TG levels of Q3 or Q4 group were
higher than those of Q1 group in youth (p <0.05). The TC
levels of the Q3 group in middle age were higher than those of the
Q2 group (p <0.05), and no significant difference was
detected in TG, HDL-C, and LDL-C levels between middle age with different TSH
levels (p >0.05). Also, no significant difference was detected in serum
lipids levels between the elderly with different TSH levels (p >0.05)
([Table 2]).
Table 2 Comparison of serum lipids between different age
groups with different serum TSH levels.
|
Group
|
Cases (n)
|
TC (mmol/l)
|
TG (mmol/l)
|
HDL-C (mmol/l)
|
LDL-C (mmol/l)
|
BMI (kg/m2)
|
SBP (mmHg)
|
DBP (mmHg)
|
FPG (mmol/l)
|
UIC (μg/l)
|
|
Youth
|
|
Q1 group
|
317
|
4.06±0.83*
|
1.26±0.82*#
|
1.48±0.35
|
2.31±0.61*
|
23.11±3.37
|
117.31±12.95
|
74.12±10.61
|
4.94±0.59
|
231.70 (164.45, 310.65)
|
|
Q2 group
|
332
|
4.13±0.80
|
1.35±0.95
|
1.47±0.36
|
2.36±0.65
|
23.34±3.55
|
119.07±13.30
|
75.45±10.52
|
4.98±0.56
|
231.10 (162.80, 313.90)
|
|
Q3 group
|
333
|
4.19±0.80
|
1.39±0.96
|
1.50±0.33
|
2.39±0.64
|
22.86±3.51
|
118.72±12.09
|
74.26±10.06
|
4.94±0.59
|
224.50 (164.55, 299.65)
|
|
Q4 group
|
285
|
4.18±0.90
|
1.41±0.95
|
1.50±0.40
|
2.38±0.66
|
23.33±3.64
|
119.25±13.35
|
74.67±9.85
|
5.03±0.63
|
236.15 (169.78, 333.83)
|
|
Middle age
|
|
Q1 group
|
110
|
4.50±0.88∆
|
1.62±0.78
|
1.49±0.38
|
2.81±0.83∆
|
24.10±2.87
|
127.99±15.15
|
81.53±10.64
|
5.35±0.68
|
209.60 (152.95, 309.55)
|
|
Q2 group
|
102
|
4.47±0.89*
|
1.63±1.07&
|
1.51±0.32
|
2.75±0.72∆
|
23.83±2.86
|
128.64±13.80
|
80.94±9.93
|
5.61±1.69
|
204.40 (147.18, 305.73)
|
|
Q3 group
|
110
|
4.75±0.83∆&
|
1.64±1.50
|
1.48±0.31
|
2.92±0.62∆
|
24.09±2.79
|
128.25±14.70
|
80.45±10.21
|
5.37±0.62
|
227.60 (150.50, 295.20)
|
|
Q4 group
|
145
|
4.70±0.87∆&
|
1.73±1.19
|
1.53±0.36
|
2.87±0.61∆
|
24.03±2.98
|
128.76±16.46
|
81.05±10.76
|
5.49±1.16
|
200.00 (145.05, 330.20)
|
|
Elderly
|
|
Q1 group
|
63
|
4.73±1.08
|
1.62±0.97
|
1.52±0.34
|
2.89±0.73∆
|
24.43±2.92
|
141.75±22.54
|
78.90±12.36
|
5.78±1.30
|
213.50 (162.40, 292.10)
|
|
Q2 group
|
58
|
4.90±1.47∆
|
1.44±1.03
|
1.64±0.43∆
|
2.93±0.99∆
|
23.41±3.13
|
141.93±18.80
|
81.10±11.63
|
5.61±0.88
|
220.40 (142.58, 303.43)
|
|
Q3 group
|
48
|
4.55±0.94
|
1.80±1.04
|
1.51±0.46
|
2.82±0.81∆
|
24.65±3.06
|
143.10±22.20
|
79.04±10.81
|
5.76±0.87
|
219.25 (156.60, 217.40)
|
|
Q4 group
|
59
|
4.63±1.08
|
1.88±1.32
|
1.58±0.60
|
2.86±0.80∆
|
24.66±3.72
|
144.49±17.36
|
81.12±13.10
|
5.84±1.85
|
208.10 (143.30, 270.00)
|
Youth: 18–44 years; Middle age: 45–59 years; Elderly:
≥60 years. Q1 group: TSH (0.27–1.68)
mIU/l; Q2 group: TSH (1.69–2.35)
mIU/l; Q3 group: TSH (2.36–3.07)
mIU/l; Q4 group: TSH (3.08–4.20)
mIU/l. * p <0.05: Compared with
Q3 group at the same age; # p <0.05:
Compared with Q4 group at the same age. ∆
p <0.05: Compared with youth group at the same TSH level;
& p <0.05 compared with elderly group at the
same TSH level.
The LDL-C levels of middle age or elderly were higher than those of youth at the
same TSH levels (all p <0.05). The TC levels of middle age in
Q1, Q3, or Q4 group were higher than those
of youth (all p <0.05), while the TC and HDL-C levels of elderly in the
Q2 group were higher than those of youth (p <0.05) ([Table 2]). The TC levels of middle age in
Q3 or Q4 group were higher than those of elderly (p
<0.05), and TG levels in Q2 group were higher than those of
elderly (p <0.05) ([Table
2]).
Comparison of serum lipids between total population or different gender
groups with different serum TSH levels
After adjusting for age, BMI, SBP, DBP, FPG, and UIC, the TC, TG, and LDL-C
levels in the Q3 group were higher than those in the Q1
group (p <0.05), and the TG levels of the Q4 group were
higher than those of Q1 group in the total population (p
<0.05). The TG levels of the Q3 group were significantly
higher than those of Q1 group in males (p <0.05). The LDL-C
levels of the Q3 group were significantly higher than those in the
Q1 group in females (p <0.05) ([Table 3]).
Table 3 Comparison of serum lipids between total population
or different gender groups with different serum TSH levels.
|
Group
|
Cases (n)
|
TC (mmol/l)
|
TG (mmol/l)
|
HDL-C (mmol/l)
|
LDL-C (mmol/l)
|
Age (years)
|
BMI (kg/m2)
|
SBP (mmHg)
|
DBP (mmHg)
|
FPG (mmol/l)
|
UIC (μg/l)
|
|
Total
|
|
Q1 group
|
490
|
4.25±0.91*
|
1.39±0.85*#
|
1.49±0.36
|
2.49±0.73*
|
40.34±14.82
|
23.50±3.25
|
122.85±17.20
|
76.40±11.29
|
5.14±0.80
|
223.90 (159.53, 309.80)
|
|
Q2 group
|
492
|
4.29±0.96
|
1.42±0.99
|
1.50±0.36
|
2.50±0.75
|
39.70±14.00
|
23.45±3.37
|
123.75±16.07
|
77.25±10.84
|
5.19±0.99
|
223.40 (157.40, 309.10)
|
|
Q3 group
|
491
|
4.35±0.85
|
1.48±1.12
|
1.50±0.34
|
2.55±0.70
|
39.56±13.70
|
23.31±3.38
|
123.24±15.89
|
76.11±10.51
|
5.12±0.68
|
224.45 (161.33, 292.95)
|
|
Q4 group
|
489
|
4.39±0.94
|
1.56±1.09
|
1.52±0.42
|
2.58±0.71
|
41.67±14.22
|
23.70±3.38
|
125.12±17.00
|
77.34±11.00
|
5.27±1.06
|
221.30 (154.33, 317.45)
|
|
Males
|
|
Q1 group
|
301
|
4.29±0.87
|
1.50±0.86*
|
1.40±0.32
|
2.59±0.72
|
40.86±14.23
|
24.25±3.17
|
124.47±14.43
|
78.41±10.90
|
5.21±0.88
|
219.60 (157.60, 295.50)
|
|
Q2 group
|
290
|
4.35±0.89
|
1.55±0.94
|
1.39±0.33
|
2.60±0.72
|
40.93±13.79
|
24.14±3.24
|
126.11±14.89
|
79.34±10.35
|
5.27±1.15
|
222.65 (165.23, 303.03)
|
|
Q3 group
|
253
|
4.37±0.80
|
1.70±1.35
|
1.39±0.32
|
2.62±0.67
|
39.33±14.31
|
24.04±3.15
|
124.82±14.36
|
78.51±9.79
|
5.18±0.73
|
223.90 (159.85, 287.35)
|
|
Q4 group
|
233
|
4.36±0.93
|
1.69±1.09
|
1.36±0.39
|
2.63±0.70
|
40.97±14.42
|
24.52±3.44
|
126.45±15.49
|
79.71±10.74
|
5.26±0.81
|
214.30 (150.05, 292.20)
|
|
Females
|
|
Q1 group
|
189
|
4.18±0.98
|
1.21±0.79
|
1.63±0.37
|
2.34±0.71*
|
39.52±15.71
|
22.30±3.02
|
120.27±20.64
|
73.20±11.20
|
5.02±0.64
|
233.20 (165.00, 326.50)
|
|
Q2 group
|
202
|
4.22±1.04
|
1.23±1.02
|
1.64±0.36
|
2.37±0.77
|
37.93±14.15
|
22.46±3.32
|
120.35±17.10
|
74.26±10.84
|
5.07±0.66
|
228.40 (144.25, 315.40)
|
|
Q3 group
|
238
|
4.34±0.90
|
1.25±0.72
|
1.61±0.31
|
2.49±0.72
|
39.80±13.05
|
22.53±3.45
|
121.55±17.25
|
73.57±10.66
|
5.05±0.63
|
225.20 (161.05, 307.50)
|
|
Q4 group
|
256
|
4.42±0.96
|
1.44±1.08
|
1.66±0.41
|
2.53±0.71
|
42.31±14.04
|
22.94±3.15
|
123.90±18.21
|
75.18±10.81
|
5.27±1.24
|
235.00 (158.83, 351.78)
|
Q1 group: TSH (0.27–1.68) mIU/l; Q2
group: TSH (1.69–2.35) mIU/l; Q3 group: TSH
(2.36–3.07) mIU/l; Q4 group: TSH
(3.08–4.20) mIU/l. * p <0.05:
Compared with Q3 group; # p <0.05:
Compared with Q4 group.
Trends of mean serum lipids levels at different TSH levels
The subjects in the three age groups were grouped according to the quartiles of
serum TSH levels within the normal range (0.27 mIU/l ≤ TSH
≤ 4.20 mIU/l). The altered trends of mean serum TC, TG, HDL-C,
and LDL-C levels in the total population, different gender groups, or different
age groups were compared.
With the increasing serum TSH levels within the normal range, mean serum TC, TG,
and LDL-C levels were increased, while HDL-C levels decreased. The trend was
more significant in females than males or the total population ([Fig. 1a]). With the increasing serum TSH
levels within the normal range, mean serum TC, TG, and LDL-C levels were
increased in youth. The trend was not significant in middle age or elderly
groups ([Fig. 1b]).
Fig. 1 Trends of mean serum lipids levels at different TSH
levels. a Trends of mean serum lipids levels in the total
population or different gender groups. b Trends of mean serum
lipids levels in different age groups.
Trends of serum TSH levels in different age groups
The TSH levels showed an increasing trend in an age-dependent manner. However,
there was not a continuous increase with age, but a peak point. The TSH levels
of females increased gradually with increasing age that peaked in the
middle-aged group, followed by a downward trend. This phenomenon was not
detected in males ([Fig. 2]).
Fig. 2 Trends of serum TSH levels in different age groups.
Discussion
The data from CHARLS (China Health and Retirement Longitudinal Study) and NHANES (US
National Health and Nutrition Examination Survey) from 2011 to 2012 were compared
among the population aged 45–75 years in China and USA. The prevalence of
dyslipidemia in the Chinese population was found to be lower than that in the US
(42.7 vs. 56.8%), and the serum levels of TG, TC, and LDL-C in the Chinese
population were lower than those in the US population [14], which suggested that lipid levels may be
susceptible to environmental, regional, dietary, and genetic factors. The prevalence
of dyslipidemia in rural Chinese adults was 32.21% [15], and that in men was higher than that in
women (42.85 vs. 26.16%) [15]. The
prevalence of high TC, high TG, low HDL-C, and high LDL-C was 5.11, 16.00, 19.27,
and 4.76%, respectively [15]. The
prevalence of dyslipidemia among adults in northwest China was 52.72% [16]. Similar to these results, the present
study showed that the total prevalence of dyslipidemia in men was significantly
higher than that in women (44.5 vs. 31.6%), while the prevalence of high TG
and low HDL-C was significantly higher than that in women. The higher prevalence of
dyslipidemia in men may be related to eating habits, greater BMI, high work
pressure, frequent social activities, or lack of physical exercise.
The serum TSH level is closely related to gender and age. NHANES III (National Health
and Nutrition Examination Survey) in the USA indicated that serum TSH levels in both
men and women increased with age, albeit the trend was obvious in women [17]. The current results also showed that the
serum TSH levels in both males and females increased with age; however, the increase
was not continuous and reached a peak. The serum TSH levels in women increased
gradually with increasing age, reached a peak in the middle age, and then showed a
downward trend, which was not obvious in men. The increasing trend may be related to
menopausal status in women. The SardiNIA study indicated that the serum TSH levels
of postmenopausal women were lower as compared to that in premenopausal women [18]. A longitudinal prospective study of
hormone changes during the transition from premenopause to postmenopause indicated
that the serum luteinizing hormone and follicle stimulating hormone were
continuously increased and a concomitant fall in estrone and estradiol were observed
in all women before menopause and in the two postmenopausal years, while
Böttner et al. reported that estradiol can increase the secretion of TSH
induced by thyrotropin-releasing hormone, and suggested that perimenopause may cause
the corresponding endocrine changes of pituitary-thyroid axis [19]
[20].
Silvia et al. found that serum TSH level was higher in women than in men [21]. Our study also found that serum TSH level
was higher in women than in men, and the serum TSH level was higher in middle age
than in youth or elderly. However, Lee et al. reported that serum TSH level was
higher in those >60 years than those aged <60 years [22]. The reason for different results may be
that serum TSH levels are affected by many other factors. For example, TSH secretion
has obvious circadian rhythm, with excessive secretion at night and lower in the
morning [23]. Concurrently, iodine intake
[24] and estrogen [25] are also shown to affect serum TSH
levels.
The changes in the serum TSH level in normal reference range were related to TC, TG,
and LDL-C [26]. The TG level was higher in
subjects with TSH at the upper limit of the normal range (2.5–4.5
mU/l) than in subjects with TSH at the lower limit of the normal range
(0.3–2.5 mU/l) [27]. Jing et
al. reported that the TG and LDL-C levels in the females with serum TSH level
4.001–4.940 mIU/l were higher than those with TSH levels
0.350–1.000 mIU/l, 1.001–2.500 mIU/l or
2.501–4.000 mIU/l; the TG levels in the males with TSH level
4.001–4.940 mIU/l was higher than those with TSH levels
0.350–1.000 mIU/l, 1.001–2.500 mIU/l or
2.501–4.000 mIU/l [28]. In the
present study, the serum LDL-C levels in the females with serum TSH levels
2.36–3.07 mIU/l were significantly higher than those with TSH levels
0.27–1.68 mIU/l. The serum TG levels in males with TSH levels
2.36–3.07 mIU/l was higher than those with TSH level
0.27–1.68 mIU/l. These results indicated that even within the normal
range, subjects with relatively high TSH levels might be more prone to
dyslipidemia.
Reportedly, the associations between serum TSH levels and serum lipids were
independent of thyroid hormones, and also greatly influenced by gender [29]. The increase in TSH level in the normal
range might also be a risk factor for dyslipidemia, especially in women with normal
high levels and subclinical hypothyroidism [30]. In the present study with increasing serum TSH levels within the
normal range, serum TC, TG, and LDL-C levels were increased, while HDL-C levels
decreased, especially in women, which was consistent with the results of the study
by Hunt et al. [26]. For every 1 mIU/l
increase in serum TSH concentration, the TG concentration increased by 0.095
mmol/l, and the serum TSH level of patients with hypertriglyceridemia was
higher than that in those with normal TG level [31]. The correlation between serum TSH levels and serum lipids might be
influenced by estrogen. Reduced estrogen production from ovaries might lead to
increased serum TC and LDL-C and decreased HDL-C levels [32].
Besides gender, age can influence the correlation between thyroid function and lipid
profiles [33]. Juan et al. divided the
subjects with normal thyroid function into five subgroups based on the quartiles of
TSH within the age-related reference range, which indicated that the serum TC and
LDL-C levels of Q5 group were higher than those of Q1 group
only in subjects aged <60 years, and no significant difference was observed
in serum lipid levels between those aged >60 years with different TSH levels
[34]. This study also showed that serum TC
and LDL-C levels of the Q3 group were higher than those of the
Q1 group, and the TG levels of the Q3 or Q4
group were higher than those of Q1 group in youth. In addition, serum TC
levels of the Q3 group were higher than those of the Q2 group
in the middle age. Also, no significant difference was detected in the serum lipids
levels between the elderly with different TSH levels, which might be related to the
relatively small sample size in the elderly group. The subjects of this study had
normal thyroid function, while the elderly had more thyroid diseases [35], which might be the reason for the small
sample size of the elderly.
TSH is the main regulator of lipid metabolism and is one of the major substances to
maintain normal lipid. In addition, TSH can regulate the expression of hepatocyte
genes and is closely related to the destruction of lipid homeostasis [36]. Furthermore, it has been found that the
expression of TSHR is not only limited to the membrane of thyroid follicular cells
but also in many parts of extra-thyroid tissues, such as fat cells and liver; thus,
it is deemed as a major regulator of adipocyte differentiation [37].
Nevertheless, the current study has several limitations. First, we did not measure
the levels of thyroid hormone in the subjects with normal TSH levels; hence, their
potential association with serum lipids was not evaluated. Second, this was a
cross-sectional study and was not designed as a long-term prospective study. Hence,
most subjects visited our institution only once, due to which, we defined euthyroid
on a single measurement of TSH, which might not reflect the correlations between the
serum TSH levels within normal range and serum lipids. Finally, this study lacked
the detection of cell levels, particularly the effect of TSH on lipid metabolism
pathways in hepatocytes or adipocytes, which made it impossible to reveal the
molecular mechanisms underlying the effect of serum normal TSH levels on serum
lipids.
Conclusion
In conclusion, the current study showed that the serum normal TSH levels were closely
related to serum lipid profiles. The serum lipids levels were higher in youth or
middle age group with high TSH levels in the normal range. At the same normal TSH
levels, the serum lipid levels of middle age or elderly were higher than those of
youth. With the rising TSH levels, serum TC, TG, and LDL-C levels were increased
gradually, and HDL-C levels decreased, especially in females.
