General characteristics of the study population
The general clinical information all patients was showed in Table 1.The present study included 117 patients (34 males, 83 females). The average age was 45.35 ± 12.78 years, BMI was 22.55 ± 3.38 kg/m2. The prevalence of NAFLD was 11.97% in this hyperthyroidism population. Patients with NAFLD had lower FT3, FT4 levels (p < 0.05) and higher BMI, Wc, TG, TC, LDL levels (p < 0.05, respectively) than patients without NAFLD. There were no significant differences in age, gender, blood pressure levels, TSH, ALT, AST, UA, FBG, f-INS, IL-6, HCRP and HOMA-IR between the two groups (p > 0.05).
Table 1
Clinical characteristics of 117 cases with hyperthyroidism
Characteristics
|
Total
(n = 117)
|
Without NAFLD With NAFLD P-value
(n = 103) (n = 14)
|
Age (years)
|
45.35 ± 12.78
|
44.72 ± 13.04
|
50.00 ± 9.88
|
0.148
|
Gender(M/F)
|
34/83
|
29/74
|
5/9
|
0.559
|
BMI(kg/m2)
|
22.55 ± 3.38
|
22.19 ± 3.31
|
25.23 ± 2.72
|
0.001
|
Waist circumference(cm)
|
80.82 ± 9.52
|
79.93 ± 9.19
|
90.29 ± 8.06
|
0.005
|
SBP(mmHg)
|
122.52 ± 13.79
|
121.82 ± 13.77
|
127.71 ± 13.33
|
0.115
|
DBP(mmHg)
|
74.32 ± 9.35
|
73.73 ± 9.34
|
78.71 ± 8.50
|
0.115
|
FBG(mmol༏L)
|
5.09 ± 1.08
|
5.04 ± 0.91
|
5.48 ± 1.92
|
0.159
|
FINS(mU/L)
|
8.70(6.50,10.60)
|
8.70(6.20,10.55)
|
8.90(7.35,11.63)
|
0.690
|
TG (mmol༏L)
|
0.99 ± 0.49
|
0.94 ± 0.43
|
1.36 ± 0.71
|
0.048
|
TC (mmol༏L)
|
3.45 ± 0.81
|
3.37 ± 0.76
|
4.00 ± 0.95
|
0.006
|
LDL (mmol༏L)
|
1.79 ± 0.66
|
1.72 ± 0.62
|
2.26 ± 0.76
|
0.004
|
IL6(pg/ml)
|
2.30(2.00,3.00)
|
2.30(2.00,3.00)
|
2.10(2.00,3.00)
|
0.564
|
HCRP(mg/L)
|
0.80(0.40,1.98)
|
0.80(0.40,2.05)
|
0.90(0.70,1.70)
|
0.594
|
UA(umol/L)
|
292.89 ± 69.51
|
293.14 ± 66.50
|
291.07 ± 91.53
|
0.917
|
ALT(U/L)
|
36.80 ± 33.06
|
38.32 ± 34.45
|
25.64 ± 16.96
|
0.179
|
AST(U/L)
|
27.15 ± 16.61
|
27.86 ± 17.10
|
21.86 ± 11.50
|
0.206
|
FT3(pmol/L)
|
20.42 ± 12.73
|
21.69 ± 12.57
|
11.09 ± 10.01
|
0.002
|
FT4(pmol/L)
|
54.15 ± 29.87
|
57.11 ± 29.58
|
32.41 ± 22.73
|
0.002
|
TSH(uIU/ml)
|
0.005(0.005,0.010)
|
0.005(0.005,0.010)
|
0.005(0.005,0.508)
|
0.824
|
HOMA-IR
|
1.90(1.38,2.54)
|
1.86(1.37,2.52)
|
2.26(1.56,3.22)
|
0.956
|
BMI = body-mass-index; SBP = Systolic Blood Pressure; DBP = diastolic blood pressure; FBG = fasting blood glucose; FINS = fasting insulin; TG = triglyceride; TC = Serum total cholesterol; LDL = low density lipoprotein; IL-6 = interleukin-6; HCRBP = hypersensitive C-reactive protein; UA = uric acid; ALT = alanine aminotransferase; AST = aspartate aminotransferase; FT3 = free triiodothyronine; FT4 = free thyroxine; TSH = thyroid-stimulating hormone; HOMA-IR = homeostasis model assessment for insulin resistance |
All subjects were further divided into three groups according to tertiles of FT3 level (Table2). The liver fat content (p for trend < 0.05) and the prevalence of NAFLD (p for trend < 0.05) gradually decreased with the increasing of fT3 (Fig. 1a-b). In addition, the levels of BMI, TG, TC, and LDL-c gradually decreased, and the levels of ALT and AST gradually increased with the increasing of fT3 (p for trend < 0.01). There were no significant differences in gender, waist circumference, blood pressure level, fasting blood glucose, fasting insulin, uric acid, IL-6, HCRP and HOMA-IR among the three groups (p > 0.05). After adjustment for age, gender, and BMI, the association of liver fat content still reached the statistical significance (p < 0.01).
Table 2
clinical characteristics of all cases by tertiles of free triiodothyronine
FT3
|
T1(≦12.70 pmol/L)
|
T2(12.71 ~ 25.80 pmol/L)
|
T3(༞25.80 pmol/L)
|
P for trend
|
Age(years)
|
49.9 ± 11.9
|
46.1 ± 13.8
|
40.1 ± 10.8※☆
|
0.002
|
Gender(M/F)
|
14/25
|
11/28
|
9/30
|
0.455
|
FT4(pmol/L)
|
25.28 ± 10.26
|
48.41 ± 14.11※
|
88.78 ± 17.28※☆
|
< 0.001
|
TSH(uIU/ml)
|
0.01(0.005,1.470)
|
0.005(0.005,0.010)※
|
0.005(0.005,0.010)※
|
< 0.001
|
BMI(kg/m2)
|
23.41 ± 3.30
|
23.40 ± 3.41
|
20.85 ± 2.82※☆
|
< 0.001
|
Waist circumference(cm)
|
83.17 ± 8.82
|
81.43 ± 10.19
|
77.79 ± 8.95※
|
0.113
|
SBP(mmHg)
|
121.46 ± 13.26
|
124.72 ± 10.94
|
121.38 ± 16.68
|
0.480
|
DBP(mmHg)
|
74.92 ± 9.10
|
75.79 ± 8.54
|
72.26 ± 10.21
|
0.221
|
FBG(mmol༏L)
|
5.01 ± 1.30
|
5.01 ± 0.79
|
5.25 ± 1.09
|
0.541
|
FINS(mU/L)
|
8.30(5.50,9.70)
|
7.90(5.80,11.1)
|
9.20(7.00,11.00)
|
0.367
|
TG(mmol༏L)
|
1.03 ± 0.48
|
1.14 ± 0.58
|
0.79 ± 0.28※☆
|
0.006
|
TC(mmol༏L)
|
3.91 ± 0.85
|
3.47 ± 0.77※
|
2.94 ± 0.43※☆
|
< 0.001
|
LDL(mmol༏L)
|
2.23 ± 0.63
|
1.76 ± 0.62※
|
1.36 ± 0.38※☆
|
< 0.001
|
IL6(pg/ml)
|
2.20(2.00,3.00)
|
2.10(2.00,2.58)
|
2.60(2.10,3.38)
|
0.352
|
HCRP(mg/L)
|
0.80(0.40,1.98)
|
0.70(0.30,2.20)
|
1.00(0.45,2.15)
|
0.389
|
UA(umol/L)
|
295.90 ± 77.90
|
282.28 ± 56.85
|
300.68 ± 72.63
|
0.486
|
ALT(U/L)
|
24.92 ± 19.76
|
36.79 ± 26.95※
|
48.69 ± 43.93※
|
0.006
|
AST(U/L)
|
21.46 ± 10.29
|
26.36 ± 13.41
|
33.62 ± 21.91※
|
0.004
|
Liver fat content(%)
|
6.75 ± 3.45
|
6.14 ± 4.34
|
4.01 ± 2.43※☆
|
0.002
|
With NAFLD/without NAFLD
|
10/29
|
3/36
|
1/38※
|
0.004
|
HOMA-IR
|
1.70(1.11,2.64)
|
1.76(1.19,2.55)
|
2.04(1.63,2.54)
|
0.289
|
※ P༜0.05 versus T1 group,; P༜0.05 versus T2 group |
Significant correlation was found between fT3 and liver fat content, the correlation was significant after adjusting for age, gender and BMI (Fig. 1c, Table 3 ). Pearson correlation analysis showed that FT3 was negatively correlated with BMI, waist circumference, TG, TC and LDL, and positively correlated with ALT and AST (Table3). The association of FT3 with TC, LDL, ALT and AST were still significant after adjusting for age, gender and BMI (P < 0.01).
Table 3
Pearson correlation analysis of factors associated with FT3 and liver fat content
index
|
Pearson correlation analysis (P-value)
|
Adjusted for age, gender (P-value)
|
Adjusted for age, gender, BMI (P-value)
|
|
Liver fat content
|
FT3
|
Liver fat content
|
FT3
|
Liver fat content
|
FT3
|
|
R
|
P-value
|
R
|
P-value
|
R
|
P-value
|
R
|
P-value
|
R
|
P-value
|
R
|
P-value
|
Age(years)
|
NS
|
-0.315
|
0.001
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
BMI(kg/m2)
|
0.337
|
< 0.001
|
-0.347
|
< 0.001
|
0.321
|
< 0.001
|
-0.292
|
0.002
|
-
|
-
|
-
|
-
|
Waist circumference(cm)
|
0.300
|
0.006
|
-0.219
|
0.049
|
0.293
|
0.009
|
NS
|
NS
|
NS
|
SBP(mmHg)
|
NS
|
NS
|
NS
|
NS
|
NS
|
NS
|
DBP(mmHg)
|
NS
|
NS
|
NS
|
NS
|
NS
|
NS
|
FT3(pmol/L)
|
-0.328
|
< 0.001
|
-
|
-
|
-0.316
|
0.001
|
-
|
-
|
-0.245
|
0.009
|
-
|
-
|
FT4(pmol/L)
|
-0.305
|
0.001
|
0.937
|
< 0.001
|
-0.291
|
0.002
|
0.930
|
< 0.001
|
-0.216
|
0.021
|
0.923
|
< 0.001
|
TSH(uIU/ml)
|
NS
|
-0.341
|
< 0.001
|
NS
|
-0.325
|
< 0.001
|
NS
|
-0.275
|
0.003
|
TG(mmol/L)
|
0.284
|
0.002
|
-0.239
|
0.011
|
0.274
|
0.004
|
-0.191
|
0.046
|
0.209
|
0.029
|
NS
|
TC(mmol/L)
|
0.331
|
< 0.001
|
-0.547
|
< 0.001
|
0.323
|
0.001
|
-0.519
|
< 0.001
|
0.286
|
0.003
|
-0.495
|
< 0.001
|
LDL(mmol/L)
|
0.346
|
< 0.001
|
-0.543
|
< 0.001
|
0.333
|
< 0.001
|
-0.513
|
< 0.001
|
0.301
|
0.001
|
-0.492
|
< 0.001
|
IL6(pg/ml)
|
NS
|
NS
|
-0.194
|
0.048
|
NS
|
NS
|
NS
|
HCRP(mg/L)
|
NS
|
NS
|
-0.240
|
0.012
|
NS
|
-0.215
|
0.026
|
NS
|
UA(umol/L)
|
NS
|
NS
|
NS
|
NS
|
NS
|
NS
|
|
|
|
ALT(U/L)
|
NS
|
0.310
|
0.001
|
NS
|
0.338
|
< 0.001
|
NS
|
0.336
|
< 0.001
|
AST(U/L)
|
NS
|
0.342
|
< 0.001
|
NS
|
0.374
|
< 0.001
|
NS
|
0.375
|
< 0.001
|
HOMA
|
NS
|
NS
|
NS
|
NS
|
NS
|
NS
|
As shown in Table 4, multiple linear regression analysis was used to analyze the independent risk factors associated with liver fat content in hyperthyroidism patients. Model 1 included FT3, FT4, TSH, and BMI, and adjusted for age and gender. The results showed that FT3 (p < 0.01) and BMI (p < 0.01) were independently correlated with the liver fat content. The full model 2 further included the FT3, FT4, TSH, TG, CHOL, LDL, systolic blood pressure, diastolic blood pressure, UA, IL − 6, HCRP as the independent variables, and adjusted for age, gender and BMI. The results showed that FT3 (p < 0.05) and TG (p < 0.05) were independently correlated with liver fat content.
Table 4
Multiple linear regression analysis of independent factors associated with liver fat content
Dependent variable
|
Model 1※
|
Model 2☆
|
Independent variable
|
β
|
P-value
|
Independent variable
|
β
|
P-value
|
Liver fat content
|
FT3
|
-0.072
|
0.009
|
FT3
|
-0.059
|
0.016
|
|
BMI
|
0.281
|
0.007
|
TG
|
1.461
|
0.013
|
※Model 1 FT3, FT4, TSH, and BMI were included as the independent variables, adjusted with age and gender;☆ Model 2 FT3, FT4, TSH, TG, CHOL, LDL, systolic blood pressure, diastolic blood pressure, UA, IL-6, and HCRP were included as the independent variables, adjusted with age, gender and BMI. |
In the binary logistic regression analysis (Table 5), after adjustment with age and gender, FT3, FT4, TSH, and BMI tertiles were used and independent variables, and the results showed FT3 (OR 0.297, 95% CI.0.106ཞ0.832), and BMI (OR 4.585, 95% CI.1.488ཞ14.128) was independently associated with NAFLD. In full Model 2, FT4, TSH, TG, CHOL, LDL, Systolic blood pressure, diastolic blood pressure, UA, IL6, and HCRP tertiles were included, adjusted variable of age, gender and BMI. The results showed FT3 (OR 0.267, 95% CI.0.087 ~ 0.817) were still independently associated with NAFLD.
Table 5
Binary logistic regression analysis of risk factors for NAFLD
Binary logistic regression analysis
|
Independent
variable
|
P-value
|
OR
|
95% C.l.
|
Model1※
|
FT3
|
0.021
|
0.297
|
0.106–0.832
|
|
BMI
|
0.008
|
4.585
|
1.488–14.128
|
Model2☆
|
FT3
|
0.021
|
0.267
|
0.087–0.817
|
※ Model 1 tertiles of FT3, FT4, TSH, and BMI were included as the independent variables, adjusted with age and gender;☆ Model 2 tertiles of FT3, FT4, TSH, TG, CHOL, LDL, systolic blood pressure, diastolic blood pressure, UA, IL-6, and HCRP were included as the independent variables, adjusted with age, gender and BMI. |