Association between overt, subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease using magnetic resonance imaging

Table 1 Sociodemographic characteristics of the three study groups, n (%)

Variable	Control (n = 48)	Subclinical hypothyroidism (n = 48)	Overt hypothyroidism (n = 48)	P value
Gender
Female	38 (79.2)	40 (83.3)	41 (85.4)	0.792
Male	10 (20.8)	8 (16.7)	7 (14.6)
Age (years), mean ± SD	39 ± 12	39 ± 8	36 ± 9	0.209
BMI (kg/m2), mean ± SD	30.7 ± 2.3	30.7 ± 2.6	31.5 ± 2.4	0.193

P value < 0.05 is considered significant. BMI: Body mass index.

Table 2 Laboratory characteristics of study groups, mean ± SD

Variable	Overt hypothyroidism (A)	Subclinical hypothyroidism (B)	Control (C)	P value	Pairwise comparison
TSH (mIU/L)	27.6 ± 29	7.1 ± 2.4	2.5 ± 1	< 0.001	A vs B: < 0.001
					A vs C: < 0.001
					B vs C: 0.553
FT4 (ng/dL)	1 ± 0.4	1.1 ± 0.2	1.2 ± 0.2	< 0.001	A vs C: < 0.001
					B vs C: 0.009
					A vs B: 0.250
ALT (U/L)	35 ± 64.5	18.7 ± 10.2	20.6 ± 9.5	0.077	A vs B: 0.115
					A vs C: 0.203
					B vs C: 1.000
AST (U/L)	29.8 ± 33.9	20.8 ±7.4	19.7 ± 6.5	0.033	A vs B: 0.100
					A vs C: 0.051
					B vs C: 1.000
Total cholesterol (mg/dL)	206.8 ± 37.9	178 ± 30.8	151.6 ± 35.5	< 0.001	A vs B: < 0.001
					A vs C: < 0.001
					B vs C: < 0.001
High density lipoprotein (mg/dL)	50.4 ± 12.5	48.9 ± 12.5	46.3 ± 18.7	0.381	A vs B: 1.000
					A vs C: 0.510
					B vs C: 1.000
Low density lipoprotein (mg/dL)	130.8 ± 34.2	110.4 ± 26.3	87.2 ± 36.6	< 0.001	A vs B: 0.008
					A vs C: < 0.001
					B vs C: 0.002
Triglycerides (mg/dL), median (range)	107 (31-356)	84 (31-322)	73.5 (37-344)	0.004	A vs B: 0.032
					A vs C: 0.005
					B vs C: 0.564

P value < 0.05 is considered significant. TSH: Thyroid-stimulating hormone; FT4: Free thyroxine; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 3 Prevalence of metabolic dysfunction-associated steatotic liver disease among the three study groups, n (%)

Variable	Overt hypothyroidism (A) (n = 48)	Subclinical hypothyroidism (B) (n = 48)	Control (C) (n = 48)	P value	Paire-wise comparison
MASLD by ultrasound
Non-MASLD	13 (27.1)	21 (43.8)	45 (93.8)	< 0.001	A vs B: 0.135
MASLD	35 (72.9)	27 (56.3)	3 (6.3)		A vs C: < 0.001
					B vs C: < 0.001
MASLD by MRI
Non-MASLD	14 (29.2)	21 (43.8)	45 (93.8)	< 0.001	A vs B: 0.203
MASLD	34 (70.8)	27 (56.3)	3 (6.3)		A vs C: < 0.001
					B vs C: < 0.001

MASLD: Metabolic dysfunction-associated steatotic liver disease; MRI: Magnetic resonance imaging.

Table 4 Sociodemographic characteristics of metabolic dysfunction-associated steatotic liver disease and non-metabolic dysfunction-associated steatotic liver disease groups, n (%)

Variable	MASLD	Non-MASLD	P value
	n = 64/144 (%)1	n = 80/144 (%)1
Gender
Female	53 (44.5)	66 (55.5)	0.961
Male	11 (44)	14 (56)
Age (years), mean ± SD	36 ± 9	40 ± 10	0.019
BMI (kg/m2), mean ± SD	31.3 ± 2.2	30.6 ± 2.6	0.091
Duration of hypothyroidism (years), mean ± SD	4.2 ± 1.8	2.1 ± 1.2	< 0.001

¹Percentages were calculated within rows.

P value < 0.05 is considered significant. BMI: Body mass index; MASLD: Metabolic dysfunction-associated steatotic liver disease.

Table 5 Laboratory characteristics of metabolic dysfunction-associated steatotic liver disease and non-metabolic dysfunction-associated steatoic liver disease groups, mean ± SD

Variable	MASLD	Non-MASLD	P value
ALT (U/L)	30.3 ± 56.5	20.3 ± 10.1	0.123
AST (U/L)	27.2 ±29.6	20.5 ± 7.6	0.054
TSH (mIU/L)	22.9 ± 26.4	4.1 ± 3	< 0.001
FT4 (ng/dL)	1 ± 0.3	1.2 ± 0.2	< 0.001
Total cholesterol (mg/dL)	191.8 ± 40.2	168.4 ± 39.4	< 0.001
High density lipoprotein (mg/dL)	48.7 ± 11.6	48.4 ± 17.1	0.892
Low density lipoprotein (mg/dL)	118.3 ± 32.1	102.4 ± 39.3	0.009
Triglycerides (mg/dL, median (range)	106 (33-356)	76 (31-344)	< 0.001

P value < 0.05 is considered significant. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; FT4: Free thyroxine; TSH: Thyroid-stimulating hormone; MASLD: Moderate metabolic dysfunction-associated steatotic liver disease.

Table 6 Correlation between thyroid stimulating hormone and other laboratory and imaging parameters

Variable	TSH (mIU/L)		Degree of correlation
	r	P value
Age (years)	-0.12	0.163	Non-significant correlation
BMI (kg/m2)	0.08	0.348	Non-significant correlation
ALT (U/L)	0.12	0.164	Non-significant correlation
AST (U/L)	0.23	0.006	Significant little positive correlation
Total cholesterol (mg/dL)	0.38	< 0.001	Significant fair positive correlation
Triglycerides (mg/dL)	0.24	0.004	Significant little positive correlation
HDL (mg/dL)	0.13	0.131	Non-significant correlation
LDL (mg/dL)	0.33	< 0.001	Significant fair positive correlation
Fib4 score	0.26	0.168	Non-significant correlation
HF%	0.69	< 0.001	Significant good positive correlation

r is the correlation coefficient, which ranges from -1 to 1; P value < 0.05 is considered significant. BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; HDL: High density lipoprotein; LDL: Low density lipoprotein; Fib4: Fibrosis-4 index; HF%: Hepatic fat percentage.

Table 7 The degree of steatosis among the three groups by ultrasonography and magnetic resonance imaging, n (%)

Variable	Overt hypothyroidism (A)	Subclinical hypothyroidism (B)	Control (C)	P value
Sonar
Mild MASLD	14 (40)	17 (63)	3 (100)	0.046
Moderate MASLD	21 (60)	10 (37)	0 (0)
Degree by MRI
Mild MASLD	13 (38.2)	17 (63)	3 (100)	0.029
Moderate MASLD	21 (61.8)	10 (37)	0 (0)

MASLD: Moderate metabolic dysfunction-associated steatotic liver disease; MRI: Magnetic resonance imaging.

Table 8 Comparing demographic and laboratory characteristics among the mild and moderate metabolic dysfunction-associated steatotic liver disease groups, mean ± SD

Variable	Mild MASLD	Moderate MASLD	P value
Age (years)	36 ± 9	36 ± 9	0.940
BMI (kg/m2)	31 ± 2	31.7 ± 2.3	0.238
Duration of hypothyroidism (years)	4.2 ± 1.6	4.3 ± 2	0.821
ALT (U/L)	19.2 ± 8.1	42.1 ± 79.6	0.106
AST (U/L)	20.5 ± 5.3	34.2 ± 41.4	0.065
TSH (mIU/L)	13.8 ± 16.1	32.6 ± 31.5	0.005
FT4 (ng/dL)	1 ± 0.2	0.9 ± 0.4	0.039
Total cholesterol (mg/dL)	186.2 ± 32.4	197.7 ± 47	0.253
High density lipoprotein (mg/dL)	48.8 ± 10.4	48.5 ± 13	0.919
Low density lipoprotein (mg/dL)	114.2 ± 25.8	122.6 ± 37.7	0.299
HF (%)	15.9 ± 7.8	30.8 ± 3.5	< 0.001
Triglycerides (mg/dL), median (range)	105 (39-322)	107 (33-356)	0.777
Fib4 score, median (range)	0.3 (0.1-0.8)	0.3 (0.1-0.7)	0.438

P value < 0.05 is considered significant. MASLD: Moderate metabolic dysfunction-associated steatotic liver disease; BMI: Body mass index; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TSH: Thyroid-stimulating hormone; FT4: Free thyroxine; HF: Hepatic fat; Fib4: Fibrosis-4 index.

Table 9 Thyroid stimulating hormone level correlation to steatosis grading by ultrasound and magnetic resonance imaging

Variable	TSH (mIU/L)		Paire-wise comparison
	mean ± SD	P value
Ultrasound
Non-MASLD (A)	4.1 ± 3	< 0.001	A vs B: 0.023
Mild MASLD (B)	13.4 ± 16		A vs C: < 0.001
Moderate MASLD (C)	32.6 ± 31.5		B vs C: < 0.001
Degree by MRI
Non-MASLD	4.1 ± 3	< 0.001	A vs B: 0.017
Mild MASLD	13.8 ± 16.1		A vs C: < 0.001
Moderate MASLD	32.6 ± 31.5		B vs C: < 0.001

P value < 0.05 is considered significant. TSH: Thyroid stimulating hormone; MASLD: Moderate metabolic dysfunction-associated steatotic liver disease; MRI: Magnetic resonance imaging.

Table 10 The variables that were significant in the stepwise logistic regression

Variable	B	SE	OR	95%CI for OR	P value
TSH (mIU/L)	0.2	0.1	1.18	1.04-1.33	0.010

TSH: Thyroid-stimulating hormone; B: Regression coefficient; SE: Standard error; OR: Odds ratio; CI: Confidence interval.

Table 11 The variable that was significant in the stepwise logistic regression

Variable	B	SE	OR	95%CI for OR	P value
TSH (mIU/L)	0.03	0.01	1.04	1.01-1.06	0.011

TSH: Thyroid-stimulating hormone; B: Regression coefficient; SE: Standard error; OR: Odds ratio; CI: Confidence interval.

Table 12 Receiver-operating characteristic curve, with sensitivity 83% and specifity 89%, showing thyroid-stimulating hormone > 6.1 (mIU/L) is associated with a higher risk of metabolic dysfunction-associated steatotic liver disease development

Variable	Cut-off point	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)	AUC	95%CI for AUC	P value
TSH (mIU/L)	> 6.1	83	89	86	87	0.88	0.82-0.93	< 0.001

PPV: Positive predictive value; NPV: Negative predictive value; AUC: Area under the curve; CI: Confidence interval TSH: Thyroid-stimulating hormone.