Increased Thyroid Antibodies

Insulin Resistance triggers thyroid antibody production and Hashimoto thyroiditis development in Euthyroid individuals.¹Jain, Amit & Dholariya, Sagar & Masroor, Mirza & Lali, P & Chandra, Lal & Dhanwal, Dinesh. (2020). Association of Anti-TPO Antibodies with Insulin Resistance in Patients of Hypothyroidism with Metabolic Syndrome: A Cross-sectional Study. Journal of Clinical & Diagnostic Research . Oct2020, Vol. 14 Issue 10, p9-13. 5p.  MetS and Insulin Resistance is highly prevalent in hypothyroidism and anti-TPO Abs and is more associated with insulin resistance in patients of hypothyroidism with MetS and Insulin Resistance.²Blaslov K, Gajski D, Vucelić V, Gaćina P, Mirošević G, Marinković J, Vrkljan M, Rotim K. The Association Of Subclinical Insulin Resistance With Thyroid Autoimmunity In Euthyroid Individuals. Acta Clin Croat. 2020 Dec;59(4):696-702. doi: 10.20471/acc.2020.59.04.16. PMID: 34285440; PMCID: PMC8253084.^,3Zhao H, Zhang Y, Ye J, Wei H, Huang Z, Ning X, Fu X. A Comparative Study on Insulin Secretion, Insulin Resistance and Thyroid Function in Patients with Polycystic Ovary Syndrome with and without Hashimoto’s Thyroiditis. Diabetes Metab Syndr Obes. 2021;14:1817-1821^,4Gabriela Brenta, “Why Can Insulin Resistance Be a Natural Consequence of Thyroid Dysfunction?”, Journal of Thyroid Research, vol. 2011, Article ID 152850, 9 pages, 2011. https://doi.org/10.4061/2011/152850^,5Hussein, M.A., Fawzi, M., Ibrahim, A. et al. Thyroid dysfunction and insulin resistance in patients with nonalcoholic fatty liver disease. Egypt J Intern Med 30, 97–102 (2018). https://doi.org/10.4103/ejim.ejim_3_18

High thyroid autoantibodies levels are related to high fasting blood glucose levels, insulin levels, lipid parameters, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values. Patients with positive thyroid autoantibodies should be treated as having Insulin Resistance.⁶Jain, Amit & Dholariya, Sagar & Masroor, Mirza & Lali, P & Chandra, Lal & Dhanwal, Dinesh. (2020). Association of Anti-TPO Antibodies with Insulin Resistance in Patients of Hypothyroidism with Metabolic Syndrome: A Cross-sectional Study. Journal of Clinical & Diagnostic Research . Oct2020, Vol. 14 Issue 10, p9-13. 5p.  

Insulin Resistance and MetS affect secretion of TSH and are responsible for occurrence of  elevated levels of TSH in hypothyroidism.⁷Varım, Ceyhun et al. “Insulin resistance in the patients with euthyroid Hashimoto thyroiditis.” Biomedical Research-tokyo 28 (2017): 1543-1547.  Autoimmunity⁸Aksoy N, Yeler MT, Ayan NN, Ozkeskin A, Ozkan Z, Serin NO. Association [5]between thyroid hormone levels and insulin resistance and body mass index. Pak J Med Sci. 2015;31(6):1417-20. ^,9FrOhlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in [4]thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521.  and systemic inflammation¹⁰Medina G, Vera-Lastra O, Peralta-Amaro AL, Jiménez-Arellano MP, Saavedra MA, [9] Cruz-Domínguez MP, et al. Metabolic syndrome, autoimmunity and rheumatic diseases. Pharmacol Res. 2018;133:277-88.^,11Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, et al. [6]Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm. 2016;2016:6757154. is associated with occurrence of Insulin Resistance¹²Medina G, Vera-Lastra O, Peralta-Amaro AL, Jiménez-Arellano MP, Saavedra MA, [9] Cruz-Domínguez MP, et al. Metabolic syndrome, autoimmunity and rheumatic diseases. Pharmacol Res. 2018;133:277-88.^,13Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, et al. [6]Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm. 2016;2016:6757154. in hypothyroidism and MetS.¹⁴Saklayen MG. The Global epidemic of the metabolic syndrome. Curr Hypertens [8] Rep. 2018;20(2):12.  

Thyroid hormones are known to have a stimulating effect on maturation of the insulin secreting beta cells, and thyroid hormone receptors have been detected in the pancreas.¹⁵Jain, Amit & Dholariya, Sagar & Masroor, Mirza & Lali, P & Chandra, Lal & Dhanwal, Dinesh. (2020). Association of Anti-TPO Antibodies with Insulin Resistance in Patients of Hypothyroidism with Metabolic Syndrome: A Cross-sectional Study. Journal of Clinical & Diagnostic Research . Oct2020, Vol. 14 Issue 10, p9-13. 5p. They also enhance gluconeogenesis and glycogenolysis in an opposing effect to insulin,¹⁶Zinke A, Schmoll D, Zachmann M, Schmoll J, Junker H, Grempler R, et al. Expression of thyroid hormone receptor isoform alpha1 in pancreatic islets. Exp Clin Endocrinol Diabetes. 2003;111:198-202. DOI: 10.1055/s-2003-404 while being known to increase the cellular glucose uptake by expressing the glucose transporter-4 isozyme.¹⁷Raboudi N, Arem R, Jones RH, Chap Z, Pena J, Chou, Field JB. Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism. Am J Physiol. 1989;256:E159- E166. DOI: 10.1152/ajpendo.1989.256.1.E159  

Knowing that overt hypothyroidism and even subclinical hypothyroidism have been associated with disorders of glucose and insulin metabolism¹⁸Weinstein SP, O’Boyle E, Fisher M, Haber RS. Regulation of GLUT2 glucose transporter expression in liver by thyroid hormone: evidence for hormonal regulation of the hepatic glucose transport system. Endocrinology. 1994;135:649-54. DOI: 10.1210/endo.135.2.8033812 and that thyroid replacement therapy is unable to restore insulin mediated glucose uptake,¹⁹Kapadia KB, Bhatt PA, Shah JS. Association between altered thyroid state and insulin resistance. J Pharmacol Pharmacother. 2012;3:156-60. DOI: 10.4103/0976-500X.95517 while those with Insulin Resistance are showing increased anti-TPO.²⁰Peppa M, Koliaki C, Nikolopoulos P, Raptis SA. Skeletal muscle insulin resistance in endocrine disease. J Biomed Biotechnol. 2010;2010:527850. DOI: 10.1155/2010/527850^,21Blaslov K, Gajski D, Vucelić V, Gaćina P, Mirošević G, Marinković J, Vrkljan M, Rotim K. The Association Of Subclinical Insulin Resistance With Thyroid Autoimmunity In Euthyroid Individuals. Acta Clin Croat. 2020 Dec;59(4):696-702. doi: 10.20471/acc.2020.59.04.16. PMID: 34285440; PMCID: PMC8253084. 

Increased levels of thyroid antibodies can be linked to various health conditions and metabolic dysfunctions. For instance, insulin resistance can stimulate the production of thyroid antibodies, leading to the development of Hashimoto’s thyroiditis even in individuals with normal thyroid function. Moreover, metabolic syndrome (MetS) and insulin resistance are commonly observed in people with hypothyroidism, particularly those with positive anti-thyroid peroxidase antibodies (anti-TPO Abs), further exacerbating insulin resistance.

Elevated levels of thyroid autoantibodies are associated with higher fasting blood glucose levels, insulin levels, lipid parameters, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) values. Consequently, individuals with positive thyroid autoantibodies should be managed as having insulin resistance.

Insulin resistance and MetS can also influence the secretion of thyroid-stimulating hormone (TSH), contributing to elevated TSH levels in hypothyroidism. Additionally, autoimmunity and systemic inflammation are implicated in the development of insulin resistance in individuals with hypothyroidism and MetS.

Thyroid hormones play a crucial role in insulin secretion and glucose metabolism. They promote the maturation of insulin-secreting beta cells in the pancreas and enhance glucose uptake in cells through the expression of glucose transporter-4 isozyme. However, thyroid hormones also exert opposing effects to insulin by stimulating gluconeogenesis and glycogenolysis.

It’s noteworthy that both overt and subclinical hypothyroidism have been associated with disruptions in glucose and insulin metabolism. Despite thyroid replacement therapy, insulin-mediated glucose uptake may not be fully restored in individuals with insulin resistance, who often exhibit increased levels of anti-TPO antibodies. Therefore, addressing thyroid function and insulin resistance concurrently is essential for managing metabolic health effectively.

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References

• 1
  Jain, Amit & Dholariya, Sagar & Masroor, Mirza & Lali, P & Chandra, Lal & Dhanwal, Dinesh. (2020). Association of Anti-TPO Antibodies with Insulin Resistance in Patients of Hypothyroidism with Metabolic Syndrome: A Cross-sectional Study. Journal of Clinical & Diagnostic Research . Oct2020, Vol. 14 Issue 10, p9-13. 5p.
• 2
  Blaslov K, Gajski D, Vucelić V, Gaćina P, Mirošević G, Marinković J, Vrkljan M, Rotim K. The Association Of Subclinical Insulin Resistance With Thyroid Autoimmunity In Euthyroid Individuals. Acta Clin Croat. 2020 Dec;59(4):696-702. doi: 10.20471/acc.2020.59.04.16. PMID: 34285440; PMCID: PMC8253084.
• 3
  Zhao H, Zhang Y, Ye J, Wei H, Huang Z, Ning X, Fu X. A Comparative Study on Insulin Secretion, Insulin Resistance and Thyroid Function in Patients with Polycystic Ovary Syndrome with and without Hashimoto’s Thyroiditis. Diabetes Metab Syndr Obes. 2021;14:1817-1821
• 4
  Gabriela Brenta, “Why Can Insulin Resistance Be a Natural Consequence of Thyroid Dysfunction?”, Journal of Thyroid Research, vol. 2011, Article ID 152850, 9 pages, 2011. https://doi.org/10.4061/2011/152850
• 5
  Hussein, M.A., Fawzi, M., Ibrahim, A. et al. Thyroid dysfunction and insulin resistance in patients with nonalcoholic fatty liver disease. Egypt J Intern Med 30, 97–102 (2018). https://doi.org/10.4103/ejim.ejim_3_18
• 6
  Jain, Amit & Dholariya, Sagar & Masroor, Mirza & Lali, P & Chandra, Lal & Dhanwal, Dinesh. (2020). Association of Anti-TPO Antibodies with Insulin Resistance in Patients of Hypothyroidism with Metabolic Syndrome: A Cross-sectional Study. Journal of Clinical & Diagnostic Research . Oct2020, Vol. 14 Issue 10, p9-13. 5p.
• 7
  Varım, Ceyhun et al. “Insulin resistance in the patients with euthyroid Hashimoto thyroiditis.” Biomedical Research-tokyo 28 (2017): 1543-1547.
• 8
  Aksoy N, Yeler MT, Ayan NN, Ozkeskin A, Ozkan Z, Serin NO. Association [5]between thyroid hormone levels and insulin resistance and body mass index. Pak J Med Sci. 2015;31(6):1417-20. 
• 9
  FrOhlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in [4]thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521. 
• 10
  Medina G, Vera-Lastra O, Peralta-Amaro AL, Jiménez-Arellano MP, Saavedra MA, [9] Cruz-Domínguez MP, et al. Metabolic syndrome, autoimmunity and rheumatic diseases. Pharmacol Res. 2018;133:277-88.
• 11
  Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, et al. [6]Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm. 2016;2016:6757154.
• 12
  Medina G, Vera-Lastra O, Peralta-Amaro AL, Jiménez-Arellano MP, Saavedra MA, [9] Cruz-Domínguez MP, et al. Metabolic syndrome, autoimmunity and rheumatic diseases. Pharmacol Res. 2018;133:277-88.
• 13
  Mancini A, Di Segni C, Raimondo S, Olivieri G, Silvestrini A, Meucci E, et al. [6]Thyroid hormones, oxidative stress, and inflammation. Mediators Inflamm. 2016;2016:6757154.
• 14
  Saklayen MG. The Global epidemic of the metabolic syndrome. Curr Hypertens [8] Rep. 2018;20(2):12.
• 15
  Jain, Amit & Dholariya, Sagar & Masroor, Mirza & Lali, P & Chandra, Lal & Dhanwal, Dinesh. (2020). Association of Anti-TPO Antibodies with Insulin Resistance in Patients of Hypothyroidism with Metabolic Syndrome: A Cross-sectional Study. Journal of Clinical & Diagnostic Research . Oct2020, Vol. 14 Issue 10, p9-13. 5p.
• 16
  Zinke A, Schmoll D, Zachmann M, Schmoll J, Junker H, Grempler R, et al. Expression of thyroid hormone receptor isoform alpha1 in pancreatic islets. Exp Clin Endocrinol Diabetes. 2003;111:198-202. DOI: 10.1055/s-2003-404
• 17
  Raboudi N, Arem R, Jones RH, Chap Z, Pena J, Chou, Field JB. Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism. Am J Physiol. 1989;256:E159- E166. DOI: 10.1152/ajpendo.1989.256.1.E159  
• 18
  Weinstein SP, O’Boyle E, Fisher M, Haber RS. Regulation of GLUT2 glucose transporter expression in liver by thyroid hormone: evidence for hormonal regulation of the hepatic glucose transport system. Endocrinology. 1994;135:649-54. DOI: 10.1210/endo.135.2.8033812
• 19
  Kapadia KB, Bhatt PA, Shah JS. Association between altered thyroid state and insulin resistance. J Pharmacol Pharmacother. 2012;3:156-60. DOI: 10.4103/0976-500X.95517
• 20
  Peppa M, Koliaki C, Nikolopoulos P, Raptis SA. Skeletal muscle insulin resistance in endocrine disease. J Biomed Biotechnol. 2010;2010:527850. DOI: 10.1155/2010/527850
• 21
  Blaslov K, Gajski D, Vucelić V, Gaćina P, Mirošević G, Marinković J, Vrkljan M, Rotim K. The Association Of Subclinical Insulin Resistance With Thyroid Autoimmunity In Euthyroid Individuals. Acta Clin Croat. 2020 Dec;59(4):696-702. doi: 10.20471/acc.2020.59.04.16. PMID: 34285440; PMCID: PMC8253084.