Ukr.Biochem.J. 2024; Volume 96, Issue 1, Jan-Feb, pp. 60-72

doi: https://doi.org/10.15407/ubj96.01.060

Fetuin-A level in patients with untreated thyroid dysfunction

A. S. Idan1*, M. I. Hamzah1, M. S. Khudhair2

1Clinical Biochemistry Department, Al-Nahrain University, Medicine College, Iraq;
2Internal Medicine Department, Al-Nahrain University, Medicine College, Iraq;
*e-mail: alaas3223@gmail.com

Received: 26 August 2023; Revised: 08 November 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024

Fetuin-A, a plasma glycoprotein, has been demonstrated to play an essential role in the pathogene­sis of several metabolic disorders. This study aimed to estimate fetuin-A serum level in patients with newly diagnosed primary hyperthyroidism (PHT) and subclinical hypothyroidism (SCH) and to examine its correlation with thyroid hormones level, age and sex of patients. The study involved 90 patients with untreated thyroid dysfunction verified with thyroid function test (45 with PHT and 45 with SCH) and 90 control subjects. Triiodo­thyronin (T3), tetraiodothyronin (T4), and thyroid stimulating hormone (TSH) serum concentrations were measured with enzyme-linked fluorescent assay (ELFA), fetuin-A concentration was measured with enzyme-linked immunosorbent assay (ELISA). It was demonstrated that the level of fetuin-A was significantly higher in the PHT group as compared with the control group and showed a significant positive correlation with the T3 level. In the SCH group, the level of fetuin-A was significantly lower and showed a negative correlation with TSH level. Fetuin-A level rose with age in the PHT group and was unaffected by sex in all studied groups. The perfect AUC value obtained for fetuin-A in the comparison between PHT and SCH groups suggests its potential use as a reliable diagnostic marker to differentiate between these two thyroid conditions.

Keywords: , , , , ,


References:

  1. Tran TV, Kitahara CM, Leenhardt L, de Vathaire F, Boutron-Ruault MC, Journy N. The effect of thyroid dysfunction on breast cancer risk: an updated meta-analysis. Endocr Relat Cancer. 2022;30(1):e220155. PubMed, CrossRef
  2. Ferrari SM, Fallahi P, Galetta F, Citi E, Benvenga S, Antonelli A. Thyroid disorders induced by checkpoint inhibitors. Rev Endocr Metab Disord. 2018;19(4):325-333. PubMed, CrossRef
  3. Sihite PL, Hambali A, Kamil MF, Muhsin M, Gani A, Diah M. Thyroid Heart Disease in Young Male, a Case Report. J Soc Med. 2023;2(1):24-28. CrossRef
  4. Maung AC, Cheong MA, Chua YY, Gardner DS. When a storm showers the blood clots: a case of thyroid storm with systemic thromboembolism. Endocrinol Diabetes Metab Case Rep. 2021;2021(1):20-0118. PubMed, PubMedCentral, CrossRef
  5. Soong E, Rehman S. A case of thromboembolic disease with mild hyperthyroidism. Endocrine Abstracts. 2022;81:EP1066. CrossRef
  6. Strikić Đula I, Pleić N, Babić Leko M, Gunjača I, Torlak V, Brdar D, Punda A, Polašek O, Hayward C, Zemunik T. Epidemiology of Hypothyroidism, Hyperthyroidism and Positive Thyroid Antibodies in the Croatian Population. Biology (Basel). 2022;11(3):394. PubMed, PubMedCentral, CrossRef
  7. Yamakawa H, Kato TS, Noh JY, Yuasa S, Kawamura A, Fukuda K, Aizawa Y. Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside. Front Physiol. 2021;12:606931. PubMed, PubMedCentral, CrossRef
  8. Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21(6):593-646. PubMed, CrossRef
  9. Gussekloo J, van Exel E , de Craen AJM, Meinders AE, Frölich M, Westendorp RGJ. Thyroid status, disability and cognitive function, and survival in old age. JAMA. 2004;292(21):2591-2599. PubMed, CrossRef
  10. Vanderpump MP, Tunbridge WMG. The Epidemiology of Thyroid Diseases. In: Braverman LE, Utiger RD. (Eds.) Werner and Ingbar’s the Thyroid: A Fundamental and Clinical Text. 2005;9:398-406.
  11. Vidili G, Delitala A, Manetti R. Subclinical hyperthyroidism: the cardiovascular point of view. Eur Rev Med Pharmacol Sci. 2021;25(8):3264-3271. PubMed, CrossRef
  12. Ma EZ, Kuo JH, Malek R, Turner DJ, Olson JA Jr, Slejko JF, Mullins CD, Hu Y. Total thyroidectomy is more cost-effective than radioactive iodine as an alternative to antithyroid medication for Graves’ disease. Surgery. 2023;173(1):193-200. PubMed, CrossRef
  13. França ÂS, Pinto SM, Vieira DC, Silva MT, Pinho PL. Graves disease: A new association with COVID-19? Semergen. 2023;49(2):101834. PubMed, PubMedCentral, CrossRef
  14. Vanderpump MPJ. The epidemiology of thyroid disease. Br Med Bull. 2011;99(1):39-51. PubMed, CrossRef
  15. Gozu HI, Lublinghoff J, Bircan R, Paschke R. Genetics and phenomics of inherited and sporadic non-autoimmune hyperthyroidism. Mol Cell Endocrinol. 2010;322(1-2):125-134. PubMed, CrossRef
  16. Mammen JSR. Thyroid and Aging. Endocrinol Metab Clin North Am. 2023;52(2):229-243. PubMed, CrossRef
  17. Castillo AÁ, Alfaro JMR, Boza AS. Approach to subclinical hypothyroidism in adults. Revista Médica Sinergia. 2020;5(2):358-358. CrossRef
  18. Bui RH. Management of Adults with Subclinical Hypothyroidism in Primary Care. 2021: Oklahoma City University.
  19. Saleh HM, Sheha AS, Eskander NN, Elhawatky AF, Hassen SI. Can Serum Fetuin-A be Used as a Marker for Cardiovascular Involvement in Psoriatic Patients? J Psoriasis Psoriatic Arthritis. 2023;8(2):24755303221135570.  CrossRef
  20. Sidheeque Hassan V, Hanifa M, Navik U, Bali A. Exogenous fetuin-A protects against sepsis-induced myocardial injury by inhibiting oxidative stress and inflammation in mice. Fundam Clin Pharmacol. 2023;37(3):607-617. PubMed, CrossRef
  21. Etienne Q, Lebrun V, Komuta M, Navez B, Thissen JP, Leclercq IA, Lanthier N. Fetuin-A in Activated Liver Macrophages Is a Key Feature of Non-Alcoholic Steatohepatitis. Metabolites. 2022;12(7):625. PubMed, PubMedCentral, CrossRef
  22. Dadej D, Szczepanek-Parulska E, Ruchała M. Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation. Metabolites. 2022;12(4):300. PubMed, PubMedCentral, CrossRef
  23. Wojtysiak-Duma B, Malecha-Jedraszek A, Burska A, Duma D, Donica H. Serum fetuin-A levels in patients with type 2 diabetes mellitus. Annales Universitatis Mariae Curie-Sklodowska, Sectio DDD: Pharmacia. 2010;23(2):93-99.
  24. Mori K, Emoto M, Inaba M. Fetuin-A: a multifunctional protein. Recent Pat Endocr Metab Immune Drug Discov. 2011;5(2):124-146. PubMed, CrossRef
  25. Kaushik SV, Plaisance EP, Kim T, Huang EY, Mahurin AJ, Grandjean PW, Mathews ST. Extended-release niacin decreases serum fetuin-A concentrations in individuals with metabolic syndrome. Diabetes Metab Res Rev. 2009;25(5):427-434. PubMed, CrossRef
  26. Banine F, Gangneux C, Mercier L, Le Cam A, Salier JP. Positive and negative elements modulate the promoter of the human liver-specific alpha2-HS-glycoprotein gene. Eur J Biochem. 2000;267(4):1214-1222. PubMed, CrossRef
  27. Chekol Abebe E, Tilahun Muche Z, Behaile T/Mariam A, Mengie Ayele T, Mekonnen Agidew M, Teshome Azezew M, Abebe Zewde E, Asmamaw Dejenie T, Asmamaw Mengstie M. The structure, biosynthesis, and biological roles of fetuin-A: A review. Front Cell Dev Biol. 2022;10:945287. PubMed, PubMedCentral, CrossRef
  28. Sanak D, Hutyra M, Kral M, Bartkova A, Zapletalova J, Fedorco M, Veverka T, Vindis D, Dornak T, Skala T, Skoloudik D, Taborsky M, Kanovsky P. Paroxysmal atrial fibrillation in young cryptogenic ischemic stroke: A 3-week ECG Holter monitoring study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159(2):283-287. PubMed, CrossRef
  29. Icer MA, Yıldıran H. Effects of nutritional status on serum fetuin-A level. Crit Rev Food Sci Nutr. 2020;60(11):1938-1946. PubMed, CrossRef
  30. Ghaffari A, Rafraf M, Navekar R, Sepehri B, Asghari-Jafarabadi M, Ghavami SM, Manafi N. Effects of turmeric on homocysteine and fetuin-A in patients with nonalcoholic fatty liver disease: a randomized double-blind placebo-controlled study. Iran Red Crescent Med J. 2017; 19(4):e43193. CrossRef
  31. Mukhuty A, Fouzder C, Mukherjee S, Malick C, Mukhopadhyay S, Bhattacharya S, Kundu R. Palmitate induced Fetuin-A secretion from pancreatic β-cells adversely affects its function and elicits inflammation. Biochem Biophys Res Commun. 2017;491(4):1118-1124. PubMed, CrossRef
  32. An WS, Lee SM, Son YK, Kim SE, Kim KH, Han JY, Bae HR, Rha SH, Park Y. Omega-3 fatty acid supplementation increases 1,25-dihydroxyvitamin D and fetuin-A levels in dialysis patients. Nutr Res. 2012;32(7):495-502. PubMed, CrossRef
  33. Mancio J, Barros AS, Conceicao G, Pessoa-Amorim G, Santa C, Bartosch C, Ferreira W, Carvalho M, Ferreira N, Vouga L, Miranda IM, Vitorino R, Manadas B, Falcao-Pires I, Ribeiro VG, Leite-Moreira A, Bettencourt N. Epicardial adipose tissue volume and annexin A2/fetuin-A signalling are linked to coronary calcification in advanced coronary artery disease: Computed tomography and proteomic biomarkers from the EPICHEART study. Atherosclerosis. 2020;292:75-83. PubMed, CrossRef
  34. Park HJ, Kim J, Han EJ, Park SE, Park CY, Lee WY, Oh KW, Park SW, Rhee EJ. Association of low baseline free thyroxin levels with progression of coronary artery calcification over 4 years in euthyroid subjects: the Kangbuk Samsung Health Study. Clin Endocrinol (Oxf). 2016;84(6):889-895. PubMed, CrossRef
  35. Peixoto de Miranda ÉJF, Bittencourt MS, Staniak HL, Pereira AC, Foppa M, Santos IS, Lotufo PA, Benseñor IM. Thyrotrophin levels and coronary artery calcification: Cross-sectional results of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Clin Endocrinol (Oxf). 2017;87(5):597-604. PubMed, CrossRef
  36. Zhang Y, Kim BK, Chang Y, Ryu S, Cho J, Lee WY, Rhee EJ, Kwon MJ, Rampal S, Zhao D, Pastor-Barriuso R, Lima JA, Shin H, Guallar E. Thyroid hormones and coronary artery calcification in euthyroid men and women. Arterioscler Thromb Vasc Biol. 2014;34(9):2128-2134. PubMed, CrossRef
  37. Corona G, Croce L, Sparano C, Petrone L, Sforza A, Maggi M, Chiovato L, Rotondi M. Thyroid and heart, a clinically relevant relationship. J Endocrinol Invest. 2021;44(12):2535-2544. PubMed, PubMedCentral, CrossRef
  38. Lin KH, Lee HY, Shih CH, Yen CC, Chen SL, Yang RC, Wang CS. Plasma protein regulation by thyroid hormone. J Endocrinol. 2003;179(3):367-377. PubMed, CrossRef
  39. Boone LR, Lagor WR, Moya Mde L, Niesen MI, Rothblat GH, Ness GC. Thyroid hormone enhances the ability of serum to accept cellular cholesterol via the ABCA1 transporter. Atherosclerosis. 2011;218(1):77-82. PubMed, PubMedCentral, CrossRef
  40. Gagnon A, Abujrad H, Irobi C, Lochnan HA, Sorisky A. Serum fetuin-A levels following recombinant human thyroid-stimulating hormone stimulation. Clin Invest Med. 2013;36(5):E264-E268. PubMed, CrossRef
  41. Ammar SR, Elbedewy TA, Nagy HM, Kotb NA. Relationship between serum Fetuin-A and insulin resistance in patients with hyperthyroidism. Tanta Med J. 2017;45(3):135-140. CrossRef
  42. muk BO, Yilmaz H, Topcuoglu T, Bilgir O, Çalan O, Pamuk G, Ertugrul DT. Fetuin-A levels in hyperthyroidism. Clinics (Sao Paulo). 2013;68(3):379-383. PubMed, PubMedCentral, CrossRef
  43. Lengyel I, Halmi S, Lőrincz H, Bak-Csiha S, Katkó M, Harangi M, Nagy EV, Paragh G, Bodor M, Berta E. Characterization of fetuin-A levels in patients with autoimmune thyroid disease. Atherosclerosis. 2022;355:165-166. CrossRef
  44. Deng XR, Ding L, Wang TG, Xu M, Lu JL, Li M, Zhao ZY, Chen YH, Bi YF, Xu YP, Xu Y. Serum Fetuin-A Levels and Thyroid Function in Middle-aged and Elderly Chinese. Biomed Environ Sci. 2017;30(6):455-459. PubMed, CrossRef
  45. Tseng FY, Chen YT, Chi YC, Chen PL, Yang WS. Serum levels of fetuin-A are negatively associated with log transformation levels of thyroid-stimulating hormone in patients with hyperthyroidism or euthyroidism: An observational study at a medical center in Taiwan. Medicine (Baltimore). 2018;97(46):e13254. PubMed, PubMedCentral, CrossRef
  46. Ertugrul DT, Gursoy A, Sahin M, Unal AD, Pamuk B, Berberoglu Z, Ayturk S, Tutuncu NB, Demirag NG. Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism. J Natl Med Assoc. 2008;100(4):401-405. PubMed, CrossRef
  47. Albayati AA, Hussein AAR. Role of fetuin-A and HSCRP in CVD risk in hypothyroidism IRAQI women. Biochem Cell Arch. 2020;20(Suppl.2):3877-3881.
  48. Bakiner O, Bozkirli E, Ertugrul D, Sezgin N, Ertorer E. Plasma fetuin-A levels are reduced in patients with hypothyroidism. Eur J Endocrinol. 2014;170(3):411-418. PubMed, CrossRef
  49. Muratli S, Uzunlulu M, Gonenli G, Oguz A, Isbilen B. Fetuin A as a new marker of inflammation in Hashimoto thyroiditis. Minerva Endocrinol. 2015;40(1):9-14. PubMed
  50. Bilgir O, Bilgir F, Calan M, Calan OG, Yuksel A. Comparison of pre- and post-levothyroxine high-sensitivity c-reactive protein and fetuin-a levels in subclinical hypothyroidism. Clinics (Sao Paulo). 2015;70(2):97-101. PubMed, PubMedCentral, CrossRef
  51. Jawad MM, Hussein AH. Study of Fetuin-A protein as a predictive marker for thyroid patients in Al-Najaf city. HIV Nursing. 2023;23(1):642-646.
  52. Jenkins NT, McKenzie JA, Hagberg JM, Witkowski S. Plasma fetuin-A concentrations in young and older high- and low-active men. Metabolism. 2011;60(2):265-271. PubMed, PubMedCentral, CrossRef
  53. Ou HY, Yang YC, Wu HT, Wu JS, Lu FH, Chang CJ. Serum fetuin-A concentrations are elevated in subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes. Clin Endocrinol (Oxf). 2011;75(4):450-455. PubMed, CrossRef
  54. Di Minno A, Zanobini M, Myasoedova VA, Valerio V, Songia P, Saccocci M, Di Minno MND, Tremoli E, Poggio P. Could circulating fetuin A be a biomarker of aortic valve stenosis? Int J Cardiol. 2017;249:426-430. PubMed, CrossRef
  55. Laughlin GA, Barrett-Connor E, Cummins KM, Daniels LB, Wassel CL, Ix JH. Sex-specific association of fetuin-A with type 2 diabetes in older community-dwelling adults: the Rancho Bernardo study. Diabetes Care. 2013;36(7):1994-2000. PubMed, PubMedCentral, CrossRef
  56. Jassem WE, Farahan AR. The Effect of Age and Gender on Fetuin-A and Some Biochemical parameters in Blood Sera of Iraqi patients with T2DM: A comparative study. Baghdad Sci J. 2015;12(1):197-203. CrossRef

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