Iranian Journal of Pathology

Evaluation of Serum CTRP-4 and CTRP-12 Levels in Hashimoto's Thyroiditis Patients: A Comparative Analysis with a Control Group and Their Correlation with Biochemical Factors

Document Type : Original Research

Authors

Doaa Jawad al-Husseini 1, 2
Mohsen Saravani 3
Shahin Nosratzehi 3, 4
Hamideh Akbari 5
Afsaneh Shafiei 6
Seyyed Mehdi Jafari 1, 2

1 Metabolic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran

2 Department of Biochemistry and Biophysics, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

3 Genetics of Non-communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

4 Department of Internal Medicine, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

5 Clinical Research Development Unit, Sayad Shirazi Hospital, Golestan University of Medical Science, Gorgan, Iran

6 Department of Clinical Biochemistry, School of Medicine, Iranshahr University of Medical Sciences, Iranshahr, Iran

https://doi.org/10.30699/ijp.2024.2025001.3276
Abstract
Background & Objective: Hashimoto's thyroiditis (HT) is one of the most common thyroid disorders and is characterized by manifestations attributed to thyroid gland damage and inflammatory conditions. Disturbances in thyroid hormones have physiological effects on lipoprotein metabolism and liver enzymes. CTRP family: C1q/TNF-related protein (CTRP) is an adipokine superfamily of proteins. Its essential role is anti-inflammatory activation, insulin sensitization, and regulation of blood lipids. In this study, we investigated the levels of CTRP-4 and CTRP-12 in the serum of HT patients and determined their association with biochemical factors.
Methods: The study included 60 participants, divided into HT patients and control groups. Diagnostic criteria for HT patients included anti-thyroid peroxidase antibodies (anti-TPO)>50 IU/mL. Serum levels of CTRP-4, CTRP-12, and anti-TPO were measured using an Enzyme-Linked Immunosorbent Assay.
Results: Our findings showed that the CTRP-4 and CTRP-12 levels in HT patients were higher than in the control groups (P=0.012 and P=0.003, respectively). HT patients also exhibited higher fasting blood glucose (FBG), cholesterol, TG, HDL, and LDL serum levels. Spearman's correlation analysis revealed a positive association between serum levels of CTRP-4 and CTRP-12 and anti-TPO (respectively, r= 0.295, P=0.022 and r = 0.346, P=0.007).
Conclusion: Our findings showed that the CTRP-4 and CTRP-12 levels in HT patients were higher than those in the control groups. These factors probably play a role in the pathogenesis of Hashimoto's thyroiditis. The clinical significance of these factors should be evaluated in future studies.

Highlights

  • CTRP-4 levels are significantly higher in Hashimoto's thyroiditis patients than in the control group
  • CTRP-12 levels are significantly higher in Hashimoto's thyroiditis patients than in the control group
  • There was a significant positive correlation between CTRP-4 and CTRP-12 in Hashimoto’s patients
  • There was a significant positive correlation between CTRP-4 and TSH
  • There was a significant correlation between CTRP-12 and TSH

Keywords

Anti-TPO
Autoimmune diseases
CTRP-4
CTRP-12
biochemical Factors
Hashimoto Thyroiditis

Subjects

  1. Amino N, Tada H, Hidaka Y, Hashimoto K. Hashimoto's disease and Dr. Hakaru Hashimoto. Endocr J. 2002;49(4):393-7. [DOI:10.1507/endocrj.49.393] [PMID]
  2. Erge E, Kiziltunc C, Balci SB, Atak Tel BM, Bilgin S, Duman TT, et al. A Novel Inflammatory Marker for the Diagnosis of Hashimoto's Thyroiditis: Platelet-Count-to-Lymphocyte-Count Ratio. Diseases. 2023;11(1). [DOI:10.3390/diseases11010015] [PMID]
  3. Ralli M, Angeletti D, Fiore M, D'Aguanno V, Lambiase A, Artico M, et al. Hashimoto's thyroiditis: An update on pathogenic mechanisms, diagnostic protocols, therapeutic strategies, and potential malignant transformation. Autoimmunity Reviews. 2020;19(10):102649. [DOI:10.1016/j.autrev.2020.102649] [PMID]
  4. Mincer DL, Jialal I. Hashimoto thyroiditis. 2017.
  5. Piticchio T, Frasca F, Malandrino P, Trimboli P, Carrubba N, Tumminia A, et al. Effect of gluten-free diet on autoimmune thyroiditis progression in patients with no symptoms or histology of celiac disease: a meta-analysis. Front Endocrinol (Lausanne). 2023;14: 1200372. [DOI:10.3389/fendo.2023.1200372] [PMID]
  6. Nadimi Shahraki Z, Azimi H, Ilchi N, Rohani Borj M, Pourghadamyari H, Mosallanejad S, et al. Circulating C1q/TNF-related protein-12 levels are associated with the severity of coronary artery disease. Cytokine. 2021;144:155545. [DOI:10.1016/j.cyto.2021.155545] [PMID]
  7. Moradi N, Najafi M, Sharma T, Fallah S, Koushki M, Peterson JM, et al. Circulating levels of CTRP3 in patients with type 2 diabetes mellitus compared to controls: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2020;169:108453. [DOI:10.1016/j.diabres.2020.108453] [PMID]
  8. Cao L, Tan W, Chen W, Huang H, He M, Li Q, et al. CTRP4 acts as an anti-inflammatory factor in macrophages and protects against endotoxic shock. Eur J Immunol. 2021;51(2):380-92. [DOI:10.1002/eji.202048617] [PMID]
  9. Huang X, Zhao J, Wang Q, Yan T, Gou S, Zhu X, et al. Association between plasma CTRPs with cognitive impairment and neurodegeneration of Alzheimer's disease. CNS Neurosci Ther. 2024;30(2):e14606. [DOI:10.1111/cns.14606] [PMID]
  10. Kong M, Gao Y, Guo X, Xie Y, Yu Y. Role of the CTRP family in tumor development and progression. Oncol Lett. 2021;22(4):723. [DOI:10.3892/ol.2021.12984] [PMID]
  11. Sarver DC, Xu C, Cheng Y, Terrillion CE, Wong GW. CTRP4 ablation impairs associative learning and memory. FASEB J. 2021;35(11): e21910. [DOI:10.1096/fj.202100733RR]
  12. Liu Z, Lu J, Zhang D, Niu L, Shi B. Decreased serum C1Q/TNF-related protein 4 concentrations are associated with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2021;12:20420188211059884. [DOI:10.1177/20420188211059884] [PMID]
  13. Wang L. CTRP4: a new member of the adipocytokine family. Cell Mol Immunol. 2017;14(10):868-70. [DOI:10.1038/cmi.2017.83] [PMID]
  14. Jin AP, Zhang QR, Yang CL, Ye S, Cheng HJ, Zheng YY. Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. Hum Exp Toxicol. 2021;40(12):2087-98. [DOI:10.1177/09603271211021880] [PMID]
  15. Tan BK, Lewandowski KC, O'Hare JP, Randeva HS. Insulin regulates the novel adipokine adipolin/ CTRP12: in vivo and ex vivo effects. J Endocrinol. 2014;221(1):111-9. [DOI:10.1530/JOE-13-0537] [PMID]
  16. Gorgani-Firuzjaee S, Khodabandehloo H. Circulating Levels of C1q/TNF-Related Protein-12 (CTRP-12) in Patients with Type 2 Diabetes: A Case-control Study. Journal of Kerman University of Medical Sciences. 2020;27(3):262-9.
  17. Ragusa F, Fallahi P, Elia G, Gonnella D, Paparo SR, Giusti C, et al. Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab. 2019;33(6):101367. [DOI:10.1016/j.beem.2019.101367] [PMID]
  18. Radetti G. Clinical aspects of Hashimoto's thyroiditis. Endocr Dev. 2014;26:158-70. [DOI:10.1159/000363162] [PMID]
  19. Seldin MM, Tan SY, Wong GW. Metabolic function of the CTRP family of hormones. Rev Endocr Metab Disord. 2014;15(2):111-23. [DOI:10.1007/s11154-013-9255-7] [PMID]
  20. Xu W, Zhou H, Li X, Wang L, Guo X, Yin L, et al. C1Q/TNF-related protein 4 expression correlates with herpes simplex encephalitis progression. Ann Transl Med. 2019;7(11):235. [DOI:10.21037/atm.2019.05.01] [PMID]
  21. Dai Y, Zhou J, Niu L, Hu J, Han J. Increased serum C1q/TNF-related protein 4 concentration in patients with acute coronary syndrome. Clin Chim Acta. 2022;524:187-91. [DOI:10.1016/j.cca.2021.11.015] [PMID]
  22. Fadaei R, Moradi N, Kazemi T, Chamani E, Azdaki N, Moezibady SA, et al. Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance. Cytokine. 2019;113:326-31. [DOI:10.1016/j.cyto.2018.09.019] [PMID]
  23. Cengiz H, Demirci T, Varim C, Tamer A. The effect of Thyroid Autoimmunity on Dyslipidemia in patients with Euthyroid Hashimoto Thyroiditis. Pak J Med Sci. 2021;37(5):1365-70. [DOI:10.12669/pjms.37.5.3883] [PMID]
  24. Yetkin DO, Dogantekin B. The Lipid Parameters and Lipoprotein(a) Excess in Hashimoto Thyroiditis. Int J Endocrinol. 2015;2015:952729. [DOI:10.1155/2015/952729] [PMID]
  25. Azizi F, Amouzegar A, Tohidi M, Hedayati M, Cheraghi L, Mehrabi Y. Systemic Thyroid Hormone Status in Treated Graves' Disease. Int J Endocrinol Metab. 2019;17(4):e95385. [DOI:10.5812/ijem.95385] [PMID]
  26. Liu J, Song W, Cui D. Relationship between Blood Lipid Profiles and Risk of Lupus Nephritis in Children. Int J Clin Pract. 2022;2022:6130774. [DOI:10.1155/2022/6130774] [PMID]
  27. Myasoedova E, Crowson CS, Kremers HM, Fitz-Gibbon PD, Therneau TM, Gabriel SE. Total cholesterol and LDL levels decrease before rheumatoid arthritis. Ann Rheum Dis. 2010;69(7):1310-4. [DOI:10.1136/ard.2009.122374] [PMID]
  28. Vrca VB, Mayer L, Skreb F, Rahelic D, Marusic S. Antioxidant supplementation and serum lipids in patients with Graves' disease: effect on LDL-cholesterol. Acta Pharm. 2012;62(1):115-22. [DOI:10.2478/v10007-012-0005-2] [PMID]
  29. Brazzelli V, Maffioli P, Bolcato V, Ciolfi C, D'Angelo A, Tinelli C, et al. Psoriasis and Diabetes, a Dangerous Association: Evaluation of Insulin Resistance, Lipid Abnormalities, and Cardiovascular Risk Biomarkers. Front Med (Lausanne). 2021;8:605691. [DOI:10.3389/fmed.2021.605691] [PMID]
  30. Enomoto T, Ohashi K, Shibata R, Higuchi A, Maruyama S, Izumiya Y, et al. Adipolin/ C1qdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism. J Biol Chem. 2011;286(40):34552-8. [DOI:10.1074/jbc.M111.277319] [PMID]
  31. Tan SY, Little HC, Sarver DC, Watkins PA, Wong GW. CTRP12 inhibits triglyceride synthesis and export in hepatocytes by suppressing HNF-4α and DGAT2 expression. FEBS Lett. 2020;594(19):3227-39. [DOI:10.1002/1873-3468.13895] [PMID]
  32. Luo Y, Wu X, Ma Z, Tan W, Wang L, Na D, et al. Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice. Cell Mol Immunol. 2016;13(5):688-99. [DOI:10.1038/cmi.2016.16] [PMID]
Iranian Journal of Pathology
Volume 20, Issue 1
Winter 2025
Pages 42-48

  • Receive Date 03 April 2024
  • Revise Date 19 June 2024
  • Accept Date 12 December 2024

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