Hepcidin and CRP Levels in a Sample of Iraqi Hypothyroid Patients Treated with Levothyroxine

Haider D. Abdullah; Suha Abdul-Khaliq  Al-Jowari

doi:10.30526/37.4.3480

Authors

Haider D. Abdullah Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0002-8037-9801
Suha Abdul-Khaliq Al-Jowari Department of Biology, College of Science, University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0001-8364-7755

DOI:

https://doi.org/10.30526/37.4.3480

Keywords:

Hypothyroidism, hepcidin, levothyroxine, C-Reactive protein, thyroid-stimulating hormone, triiodothyronine, thyroxine.

Abstract

Study of hypothyroidism and its relationship to the levels of the hormone hepcidin and C-reactive protein in people treated with levothyroxine. This study was carried out between November 2022 and March 2023. The study had a total of 90 male and female participants with an average age of 25 to 50 years old. All samples were obtained from both hospitals in Baghdad and the Medical Lab. The diagnosis of hypothyroidism based on symptoms and the hypothyroidism control test score led to the collection of 30 samples from healthy individuals, 30 from those with untreated hypothyroidism, and 30 additional samples. From people with hypothyroidism who were treated with levothyroxine, where the necessary tests were conducted for the three groups, Blood samples were collected in a gel tube, and serum was separated for use in their respective measurements of (TSH, T3, T4, CRP, and hepcidin. According to the results, there were no significant differences in the mean patient’s age (p=0.419) or gender distribution (p=0.638) between the three studied groups. When thyroid function tests were done on the groups that were studied, the hypothyroid patients had significantly lower levels of triiodothyronine (T3) and thyroxine (T4) and higher levels of thyroid-stimulating hormone (TSH) before treating them (p< 0.001). And the highest serum hepcidin and CRP levels (11.77 ± 0.98 and 14.61 ± 2.49 respectively) were found in group 1 patients. On the contrary, the lowest levels (7.61 ± 1.56 and 3.19 ± 0.29, respectively) were present in group 2 patients. In healthy subjects, the hepcidin and CRP levels were 8.45 ± 0.53 and 3.51 ± 0.91, respectively.Accordingly, there was a significant difference in hepcidin and CRP levels between the three studied groups, and the results showed a decrease in hepcidin and C-reactive protein after treatment.

References

Chaker, L.; Razvi, S.; Bensenor, I.M.; Azizi, F;, Pearce, E.N.; Peeters, R.P. Hypothyroidism Nature Reviews Disease Primers 2022, 8(1), 30. https://doi.org/10.1038/s41572-022-00357-7.

Hughes, K.; Eastman, C. Thyroid disease: Long-term management of hyperthyroidism and hypothyroidism. Australian Journal of General Practice 2021, 50(1-2), 36–42. https://doi.org/10.31128/ajgp-09-20-5653.

Lei, Y.; Yang, J.; Li, H.; Zhong, H.; Wan, Q. Changes in glucose-lipid metabolism, insulin resistance, and inflammatory factors in patients with autoimmune thyroid disease. Journal of Clinical Laboratory Analysis 2019, 33(7), e22929.‏ https://doi.org/10.1002/jcla.22929.

Kwiatek Majkusiak, J.; Geremek, M.; Koziorowski, D.; Tomasiuk, R.; Szlufik, S.; Friedman, A. Serum levels of hepcidin and interleukin 6 in Parkinson’s disease. Acta Neurobiologiae Experimentalis 2020, 80(3), 297-304.‏

Yu, Y.T.; Ho, C.T.; Hsu, H.S.; Li, C.I.; Davidson, L.E.; Liu, C.S.; Lin, W.Y. Subclinical hypothyroidism is associated with elevated high-sensitive C-reactive protein among adult Taiwanese. Endocrine 2013, 44, 716-722.‏ https://doi.org/10.1007/s12020-013-9915-0.

Krysiak, R.; Okopien, B. The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto's thyroiditis. The Journal of Clinical Endocrinology and Metabolism 2011, 96(7), 2206-2215. ‏https://doi.org/10.1210/jc.2010-2986.

Ahmed, M.J.; Mohammed, A.A.; Qasim, B.A. Lipid profile IN subclinical hypothyroidism: a two centers experience. Duhok Medical Journal 2019, 13(1), 56-65.‏ https://doi.org/10.31386/dmj.2019.13.1.6.

Mendes, D.; Alves, C.; Silverio, N.; Marques, F.B. Prevalence of undiagnosed hypothyroidism in Europe: a systematic review and meta-analysis. European Thyroid Journal 2019, 8(3), 130-143.‏ https://doi.org/10.1159/000499751.

Dunn, D.; Turner, C. Hypothyroidism in women. Nursing for Women's Health 2016, 20(1), 93-98.‏ DOI: https://doi.org/10.1016/j.nwh.2015.12.002.

Livingston, E.H. Subclinical hypothyroidism. Jama 2019, 322(2), 180-180.‏ https://doi.org/10.1001/jama.2019.9508.

Rosinha, P.; Dantas, R.; Alves, M.; Azevedo, T.; Inácio, I.; Esteves-Ferreira, S.; Guimarães, J. Subclinical Hypothyroidism in Pediatric Age: How Important Is Autoimmunity? Cureus 2022, 14(8), e28507. https://doi.org/10.7759%2Fcureus.28507.

Almandoz, J.P.; Gharib, H. Hypothyroidism: etiology, diagnosis, and management. Medical Clinics 2012, 96(2), 203-221.‏ https://doi.org/10.1016/j.mcna.2012.01.005.

Hueston, W.J. Treatment of hypothyroidism. American Family Physician 2001, 64(10), 1717.‏

Hennessey, J.V.; Espaillat, R. Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy. International Journal of Clinical Practice 2018, 72(2), e13062. https://doi.org/10.1111/ijcp.13062.

Kazemi Tanha, M.; Nayebifar, S.; Ghasemi, E.; Nosrat Zehi, S. Investigating the synergistic effect of Nasturtium officinale extract and High-intensity interval training on fatty acid-binding protein 4 (FABP4) and high-sensitivity C-reactive protein (hs-CRP) in overweight subclinical hypothyroid patients: a rand. Sport Physiology 2023, 14(56), 175-198.‏ https://doi.org/10.22089/spj.2022.13463.2214.

Tayde, P.S.; Bhagwat, N.M.; Sharma, P.; Sharma, B.; Dalwadi, P.P.; Sonawane, A.; Varthakavi, P.K. Hypothyroidism and depression: are cytokines the link?. Indian Journal of Endocrinology and Metabolism 2017, 21(6), 886.‏ https://doi.org/10.4103%2Fijem.IJEM_265_17.

Erge, E.; Kiziltunc, C.; Balci, S.B.; Atak Tel, B.M.; Bilgin, S.; Duman, T.T.; Aktas, G. A Novel Inflammatory Marker for the Diagnosis of Hashimoto’s Thyroiditis: Platelet-Count-to-Lymphocyte-Count Ratio. Diseases 2023, 11(1), 15.‏ https://doi.org/10.3390/diseases11010015.

Ji, J.; Sun, C.L.; Cohen, H.J.; Synold, T.; Muss, H.; Sedrak, M.S. Inflammation and clinical decline after adjuvant chemotherapy in older adults with breast cancer: Results from the Hurria older patients prospective study. Journal of Clinical Oncology 2023, 41(2), 307-315.‏ https://doi.org/10.1200/jco.22.01217.

Nemeth, E.; Ganz, T. Hepcidin and iron in health and disease. Annual Review of Medicine, 2023, 74, 261-277.‏ https://doi.org/10.1146%2Fannurev-med-043021-032816.

Hernik, A.; Szczepanek-Parulska, E.; Filipowicz, D.; Abdolall, A.; Borowczyk, M.; Wrotkowska, E.; Ruchała, M. The hepcidin concentration decreases in hypothyroid patients with Hashimoto’s thyroiditis following restoration of euthyroidism. Scientific Reports 2019, 9(1), 16222.‏ https://doi.org/10.1038/s41598-019-52715-3.

Wrighting, D.M.; Andrews, N.C. Interleukin-6 induces hepcidin expression through STAT3. Blood 2006, 108(9), 3204-3209.‏ https://doi.org/10.1182/blood-2006-06-027631.

Banzet, S.; Sanchez, H.; Chapot, R.; Bigard, X.; Vaulont, S.; Koulmann, N. Interleukin-6 contributes to hepcidin mRNA increase in response to exercise. Cytokine 2012, 58(2), 158-161.‏ https://doi.org/10.1016/j.cyto.2012.01.006.

Oppen, K.; Brede, C.; Skadberg, Ã.Y.; Steinsvik, T.; Holter, J.C.; Michelsen, A.E.; Heggelund, L. Hepcidin analysis in pneumonia-comparison of immunoassay and LC-MS/MS. Annals of Clinical Biochemistry 2023, 60(5), 298–305. https://doi.org/10.1177/00045632231159529.

Gupta, G.; Sharma, P.; Kumar, P.; Itagappa, M. Study on subclinical hypothyroidism and its association with various inflammatory markers. Journal of Clinical and Diagnostic Research: JCDR 2015, 9(11), BC04.‏ https://doi.org/10.7860%2FJCDR%2F2015%2F14640.6806.

Taddei, S.; Caraccio, N.; Virdis, A.; Dardano, A.; Versari, D.; Ghiadoni, L.; Monzani, F. Low-grade systemic inflammation causes endothelial dysfunction in patients with Hashimoto’s thyroiditis. The Journal of Clinical Endocrinology and Metabolism 2006, 91(12), 5076-5082.‏ https://doi.org/10.1210/jc.2006-1075.

Marchiori, R.C.; Pereira, L.A.; Naujorks, A.A.; Rovaris, D.L.; Meinerz, D.F.; Duarte, M. M.; Rocha, J.B. Improvement of blood inflammatory marker levels in patients with hypothyroidism under levothyroxine treatment. BMC Endocrine Disorders 2015, 15(1), 1-9. ‏ https://doi.org/10.1186/s12902-015-0032-3.

Ross, E.; Ganz, T. Hepcidin and iron in health and disease. Annals of Clinical Biochemistry, 2023, 54, 261-277. https://doi.org/10.1146%2Fannurev-med-043021-032816.

Koorts, A.M.; Viljoen, M. Acute phase proteins: Ferritin and ferritin isoforms. In: Acute phase proteins-regulation and functions of acute phase proteins. Veas, F. Edn. IntechOpen,‏ 2011. https://doi.org/10.5772/20586.

Gehrer, C.M.; Mitterstiller, A.M.; Grubwieser, P.; Meyron-Holtz, E.G.; Weiss, G.; Nairz, M. Advances in Ferritin Physiology and Possible Implications in Bacterial Infection. Indian journal of Endocrinology and Metabolism 2017, 31(4), 146.‏ https://doi.org/10.3390/ijms24054659.

Oppen, K.; Ueland, T.; Siljan, W.W.; Skadberg, Ø.; Brede, C.; Lauritzen, T.; Aukrust, P.; Steinsvik, T.; Husebye, E.; Michelsen, A.E.; Holter, J.C.; Heggelund, L. Hepcidin and Ferritin Predict Microbial Etiology in Community-Acquired Pneumonia. Open Forum Infectious Diseases 2021, 8(4), ofab082. https://doi.org/10.1093/ofid/ofab082.