J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website https://jem.elmerpub.com

Original Article

Volume 16, Number 2, April 2026, pages 70-81

From Inflammation to Endocrine Dysregulation: Thyroid Hormonal Alterations in COVID-19

↓ Figure 1. Thyroid status in patients with active COVID-19 infection (group 1). COVID-19: coronavirus disease 2019.

↓ Figure 4. ROC curve analysis for determining the optimal cut-off value of HIF-1α in COVID-19 disease. COVID-19: coronavirus disease 2019; HIF-1α: hypoxia-inducible factor-1 alpha; ROC: receiver operating characteristic.

↓ **Table 1.** Demographic Characteristics of the Participants by Group
Variable	Group 1 (n = 33)	Group 2 (n = 35)	Group 3 (n = 33)
SD: standard deviation.
Age (mean ± SD)	69.88 ± 11.89	45.24 ± 14.47	46.73 ± 13.01
Gender
Male (n, %)	15 (45.5%)	11 (31.4%)	3 (9.1%)
Female (n, %)	18 (54.5%)	24 (68.6%)	30 (90.9%)

↓ Table 1. Demographic Characteristics of the Participants by Group

Variable

Group 1 (n = 33)

Group 2 (n = 35)

Group 3 (n = 33)

SD: standard deviation.

Age (mean ± SD)

69.88 ± 11.89

45.24 ± 14.47

46.73 ± 13.01

Gender

Male (n, %)

15 (45.5%)

11 (31.4%)

3 (9.1%)

Female (n, %)

18 (54.5%)

24 (68.6%)

30 (90.9%)

↓ **Table 2.** Thyroid Parameters in the Three Study Groups
Parameters	Group 1 (n = 33)	Group 2 (n = 35)	Group 3 (n = 33)	P-value (1–2/2–3/1–3)
Values are expressed as mean ± SD and Me (IQR). Overall between-group differences were assessed using the Kruskal–Wallis test, and when appropriate, pairwise comparisons between groups were performed using the Mann–Whitney U test. A P-value < 0.05 was considered statistically significant. FT3: free triiodothyronine; FT4: free thyroxine; Tg: thyroglobulin; TPO: thyroid peroxidase; TSH: thyroid-stimulating hormone.
TSH (mIU/L)	1.35 ± 1.21 1.30 (1.32)	2.57 ± 2.95 1.78 (1.76)	4.51 ± 1.23 2.29 (3.23)	0.063/0.240/0.000
FT3 (pmol/L)	3.03 ± 0.94 2.81 (1.28)	6.52 ± 8.34 4.48 (1.33)	5.09 ± 0.87 4.98 (1.58)	0.000/0.077/0.000
FT4 (pmol/L)	21.17 ± 28.25 13.96 (2.90)	30.58 ± 40.73 14.04 (2.16)	21.50 ± 19.23 13.56 (1.91)	0.091
Tg (ng/mL)	17.66 ± 4.13 11.90 (10.57)	16.86 ± 6.02 12.38 (39.51)	17.24 ± 3.01 15.23 (19.47)	0.404
TPO (pg/mL)	137.39 ± 211.07 47.80 (113.60)	53.71 ± 134.15 16.87 (55.66)	186.94 ± 146.21 129.33 (195.00)	0.089

↓ Table 2. Thyroid Parameters in the Three Study Groups

Parameters

Group 1 (n = 33)

Group 2 (n = 35)

Group 3 (n = 33)

P-value (1–2/2–3/1–3)

Values are expressed as mean ± SD and Me (IQR). Overall between-group differences were assessed using the Kruskal–Wallis test, and when appropriate, pairwise comparisons between groups were performed using the Mann–Whitney U test. A P-value < 0.05 was considered statistically significant. FT3: free triiodothyronine; FT4: free thyroxine; Tg: thyroglobulin; TPO: thyroid peroxidase; TSH: thyroid-stimulating hormone.

TSH (mIU/L)

1.35 ± 1.21
1.30 (1.32)

2.57 ± 2.95
1.78 (1.76)

4.51 ± 1.23
2.29 (3.23)

0.063/0.240/0.000

FT3 (pmol/L)

3.03 ± 0.94
2.81 (1.28)

6.52 ± 8.34
4.48 (1.33)

5.09 ± 0.87
4.98 (1.58)

0.000/0.077/0.000

FT4 (pmol/L)

21.17 ± 28.25
13.96 (2.90)

30.58 ± 40.73
14.04 (2.16)

21.50 ± 19.23
13.56 (1.91)

0.091

Tg (ng/mL)

17.66 ± 4.13
11.90 (10.57)

16.86 ± 6.02
12.38 (39.51)

17.24 ± 3.01
15.23 (19.47)

0.404

TPO (pg/mL)

137.39 ± 211.07
47.80 (113.60)

53.71 ± 134.15
16.87 (55.66)

186.94 ± 146.21
129.33 (195.00)

0.089

↓ **Table 3.** Selected Cytokines Associated With Immune Response Differences Between Groups
Marker	Group 1 (n = 33)	Group 2 (n = 35)	Group 3 (n = 33)	P-value (1–2/2–3/1–3)
Values are expressed as mean ± SD and Me (IQR). Pairwise comparisons between groups were performed using the Mann–Whitney U test. A P-value < 0.05 was considered statistically significant. IFN-γ: interferon-gamma; IL-7: interleukin-7; IL-10: interleukin-10; IL-17A: interleukin-17A.
IL-17A (pg/mL)	29.45 ± 4.90 28.07 (3.86)	32.48 ± 27.84 25.13 (5.35)	41.91 ± 37.26 29.04 (7.71)	0.001/0.000/0.142
IL-10 (pg/mL)	4.54 ± 4.75 2.92 (2.10)	2.77 ± 2.89 1.86 (0.96)	3.10 ± 1.31 3.02 (0.83)	0.005/0.001/0.402
IL-7 (pg/mL)	36.70 ± 10.8 36.76 (13.25)	27.27 ± 8.35 26.73 (13.25)	58.06 ± 30.14 51.41 (26.13)	0.000/0.000/0.000
IFN-γ (pg/mL)	12.23 ± 3.33 11.17 (5.48)	8.64 ± 4.94 8.75 (7.83)	15.01 ± 6.17 13.12 (9.10)	0.003/0.000/0.106

↓ Table 3. Selected Cytokines Associated With Immune Response Differences Between Groups

Marker

Group 1 (n = 33)

Group 2 (n = 35)

Group 3 (n = 33)

P-value (1–2/2–3/1–3)

Values are expressed as mean ± SD and Me (IQR). Pairwise comparisons between groups were performed using the Mann–Whitney U test. A P-value < 0.05 was considered statistically significant. IFN-γ: interferon-gamma; IL-7: interleukin-7; IL-10: interleukin-10; IL-17A: interleukin-17A.

IL-17A (pg/mL)

29.45 ± 4.90
28.07 (3.86)

32.48 ± 27.84
25.13 (5.35)

41.91 ± 37.26
29.04 (7.71)

0.001/0.000/0.142

IL-10 (pg/mL)

4.54 ± 4.75
2.92 (2.10)

2.77 ± 2.89
1.86 (0.96)

3.10 ± 1.31
3.02 (0.83)

0.005/0.001/0.402

IL-7 (pg/mL)

36.70 ± 10.8
36.76 (13.25)

27.27 ± 8.35
26.73 (13.25)

58.06 ± 30.14
51.41 (26.13)

0.000/0.000/0.000

IFN-γ (pg/mL)

12.23 ± 3.33
11.17 (5.48)

8.64 ± 4.94
8.75 (7.83)

15.01 ± 6.17
13.12 (9.10)

0.003/0.000/0.106

↓ **Table 4.** Markers of Oxidative and Hypoxic Stress in the Three Study Groups
Маrkers	Group 1 (n = 33)	Group 2 (n = 35)	Group 3 (n = 33)	P-value (1–2/2–3/1–3)
Values are expressed as mean ± SD and Me (IQR). Pairwise comparisons between groups were performed using the Mann–Whitney U test. A P-value < 0.05 was considered statistically significant. HIF-1α: hypoxia-inducible factor-1 alpha; NFE2L2: nuclear factor erythroid 2-related factor 2.
HIF-1α (pg/mL)	1321.51 ± 1224.92 1035.67 (878.89)	424.33 ± 321.3 364.67 (357.71)	558.87 ± 458.98 373.96 (412.77)	0.000/0.134/0.000
NFE2L2 (pg/mL)	229.23 ± 69.04 226.90 (92.53)	185.97 ± 146.56 148.98 (120.64)	220.58 ± 107.32 214.31 (180.53)	0.004/0.069/0.595

↓ Table 4. Markers of Oxidative and Hypoxic Stress in the Three Study Groups

Маrkers

Group 1 (n = 33)

Group 2 (n = 35)

Group 3 (n = 33)

P-value (1–2/2–3/1–3)

Values are expressed as mean ± SD and Me (IQR). Pairwise comparisons between groups were performed using the Mann–Whitney U test. A P-value < 0.05 was considered statistically significant. HIF-1α: hypoxia-inducible factor-1 alpha; NFE2L2: nuclear factor erythroid 2-related factor 2.

HIF-1α (pg/mL)

1321.51 ± 1224.92
1035.67 (878.89)

424.33 ± 321.3
364.67 (357.71)

558.87 ± 458.98
373.96 (412.77)

0.000/0.134/0.000

NFE2L2 (pg/mL)

229.23 ± 69.04
226.90 (92.53)

185.97 ± 146.56
148.98 (120.64)

220.58 ± 107.32
214.31 (180.53)

0.004/0.069/0.595

↓ **Table 5.** ROC Analysis of HIF-1α to Distinguish Patients With Active COVID-19 Infection From Healthy Individuals
Variable	AUC (95% CI)	P-value	Cut-off (pg/mL)	Sensitivity (%)	Specificity (%)
AUC: area under the curve; CI: confidence interval; COVID-19: coronavirus disease 2019; HIF-1α: hypoxia-inducible factor-1 alpha; ROC: receiver operating characteristic.
HIF-1α	0.771 (0.644–0.897)	< 0.001	842.6	0.67	0.83

↓ Table 5. ROC Analysis of HIF-1α to Distinguish Patients With Active COVID-19 Infection From Healthy Individuals

Variable

AUC (95% CI)

P-value

Cut-off (pg/mL)

Sensitivity (%)

Specificity (%)

AUC: area under the curve; CI: confidence interval; COVID-19: coronavirus disease 2019; HIF-1α: hypoxia-inducible factor-1 alpha; ROC: receiver operating characteristic.

HIF-1α

0.771 (0.644–0.897)

< 0.001

842.6

0.67

0.83

↓ **Table 6.** Correlations Between Immunological and Thyroid Parameters in the Studied Groups
Correlations	Group 1	Group 2	Group 3
Data are presented as Spearman correlation coefficients (r). Statistical significance was considered at P < 0.05. FT3: free triiodothyronine; FT4: free thyroxine; IL-7: interleukin-7; IL-10: interleukin-10; TPO: thyroid peroxidase.
IL-7–TPO	r = 0.390, P = 0.049	-	-
IL-7–FT3	r = −0.440, P = 0.021	-	-
FT4–IL-10	-	r = 0.438, P = 0.014	r = −0.418, P = 0.042
FT3–IL-10	-	-	r = −0.631, P = 0.001

↓ Table 6. Correlations Between Immunological and Thyroid Parameters in the Studied Groups

Correlations

Group 1

Group 2

Group 3

Data are presented as Spearman correlation coefficients (r). Statistical significance was considered at P < 0.05. FT3: free triiodothyronine; FT4: free thyroxine; IL-7: interleukin-7; IL-10: interleukin-10; TPO: thyroid peroxidase.

IL-7–TPO

r = 0.390, P = 0.049

IL-7–FT3

r = −0.440, P = 0.021

FT4–IL-10

r = 0.438, P = 0.014

r = −0.418, P = 0.042

FT3–IL-10

r = −0.631, P = 0.001