Oxidative Stress and Thyroid Diseases: Comparison
Please note this is a comparison between Version 2 by Vivi Li and Version 1 by Karolina Jakubczyk.

Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate the oxidative profile in patients with thyroid diseases compared to the healthy population. This opens up a new perspective for investigating the role of elevated parameters of oxidative stress and damage in people with thyroid diseases, especially of neoplastic nature. An imbalance between oxidants and antioxidants is observed at different stages and in different types of thyroid diseases. The organ, which is part of the endocrine system, uses free radicals (reactive oxygen species, ROS) to produce hormones. Thyroid cells release enzymes that catalyse ROS generation; therefore, a key role is played by the internal defence system and non-enzymatic antioxidants that counteract excess ROS not utilised to produce thyroid hormones, acting as a buffer to neutralise free radicals and ensure whole-body homeostasis. An excess of free radicals causes structural cell damage, undermining genomic stability. Looking at the negative effects of ROS accumulation, oxidative stress appears to be implicated in both the initiation and progression of carcinogenesis.

  • oxidative stress
  • ROS
  • thyroid diseases
  • antioxidants

1. Introduction

Reactive oxygen species (ROS) are molecules capable of independent existence, which contain an oxygen atom and unpaired electrons [1]. ROS arise mainly as by-products in a series of bioenergetic processes of ATP synthesis in mitochondrial respiratory chains [2,3][2][3]. Inflammatory processes are an additional source of ROS [1,4][1][4]. The most common reactive oxygen species include radicals derived from the electron reduction of molecular oxygen–superoxide anion (O2•−), hydrogen peroxide (H2O2) and the more reactive hydroxyl radical (HO), released in reactions involving metal ions [5].
Obrona antyoksydacyjna organizmu przed negatywnymi skutkami ROS działa na wielu różnych platformach. Polega na zapobieganiu powstawaniu rodników, ich wymiataniu i naprawie uszkodzeń wywołanych przez ROS. Wiodącą rolę w systemie obronnym organizmu odgrywają enzymy antyoksydacyjne, rozkładające cząsteczki ROS i tym samym chroniące komórki przed nadmierną ekspozycją na ROS [ 6 , 7 , 8 ]. System naprawy uszkodzeń wywołanych przez ROS częściowo opiera się na procesach autofagii i apoptozy, eliminując uszkodzone komórki [ 9 , 10 , 11]. Pomimo szeregu wewnętrznych mechanizmów regulacji enzymatycznej, system obrony antyoksydacyjnej powinien być również wspierany przez mechanizmy nieenzymatyczne. Te ostatnie obejmują działanie cząsteczek o silnych właściwościach antyoksydacyjnych, w tym przede wszystkim glutationu, koenzymu Q10, a także substancji egzogennych – związków polifenolowych, kwasu askorbinowego, retinolu, β-karotenu i tokoferolu. Egzogennych substancji o potwierdzonych właściwościach przeciwutleniających wzmocnienia obrony antyoksydacyjnej ciała zwiększa całkowitą zdolność przeciwutleniającą [ 7 , 12 , 13 , 14 ].
Oxidative stress is an effect of redox imbalance between reactive oxygen species and antioxidant defence [9,15][6][7]. It may be caused both by the excessive production of ROS and by an inefficient antioxidant system, resulting in molecular damage [16][8]. Additionally, ROS generation in different subcellular compartments likely involves a positive feedback mechanism, creating a vicious circle of pathological conditions related to oxidative stress [17,18,19][9][10][11]. Redox homeostasis requires an equilibrium of ROS production and scavenging [20][12]. Even though the concept of oxidative stress was introduced in the 1980s, its definition and scope of research have been continually elaborated and expanded [6][13].
Thyroid diseases are a common health problem worldwide, especially among women. The occurrence of subclinical thyroid disorders, which often remain undiagnosed, is also significant [21,22,23,24][14][15][16][17]. Thyroid diseases are increasingly linked to oxidative stress [25,26,27,28][18][19][20][21]. It has been shown that thyroid dysfunction can co-occur with metabolic disorders, including obesity [29,30,31][22][23][24]. Obesity is a metabolic disease involving mitochondrial dysfunction and chronic oxidative stress, as in several metabolic disorders [32,33,34,35,36,37,38][25][26][27][28][29][30][31]. Since the incidence of thyroid diseases is increased in individuals with increased body weight, the related substrate of metabolic disorders and thyroid dysfunction seems relevant [30,31,39][23][24][32]. However, current reports do not distinguish between the causes and consequences of metabolic abnormalities, so there is a need to develop research on the pathogenesis of thyroid disorders.

2. Physiological Redox Signalling and the Role of ROS in Thyroid Function

Signalling functions in immune responses are initiated when molecular oxygen is oxidised to the reactive superoxide anion radical by the NADPH oxidase (NOX) complex, itself an additional source of ROS [4]. Subsequently, the superoxide is converted by superoxide dismutase (SOD) to H2O2. Hydrogen peroxide is associated with a signalling function regulating cellular processes, due to its capacity to reversibly modify cysteine residues [20][12]. The process alters redox signalling [17][9]. Accumulation of excessive concentrations of H2O2 activates thiolate anion (Cys-S-) oxidation pathways. This is an irreversible process, resulting in permanent protein damage [40][33]. Antioxidant systems serve a protective function, preventing intracellular accumulation of ROS by reversing the modification of cysteine residues [20][12]. The role (physiological or pathological) played by ROS depends largely on their concentration and the conditions accompanying biochemical transformations. The initial concentration dictates downstream responses [7][34]. Excessive amounts of ROS at the subcellular level activates pathways leading to damage in particularly susceptible cell structures or apoptosis [40][33]. In turn, at low physiological levels, ROS play a signalling role, essential for normal cellular processes [8,41][35][36]. Reactive oxygen species also serve as intracellular mediators produced in phagocytic cells, controlling the inflammatory response and antimicrobial defence [4]. ROS play an important role in normal thyroid function. Thyroid cells release oxidases, which catalyse ROS production [42,43,44][37][38][39]. Inositols are also involved in thyroid hormone synthesis and normal thyroid function, activating a cascade of processes including regulating TSH-dependent signalling (as a TSH transmitter) and generating H2O2 production used for iodination and coupling of iodotyrosine and iodothyronine [45,46,47,48][40][41][42][43]. Inositol deficiency or impairment of inositol cascades may result in insufficient synthesis of thyroid hormones, leading to hypothyroidism, which may be further compounded by an increased need for inositols in response to high TSH levels [45,48][40][43]. Myoinositol supplementation in hypothyroid patients effectively lowers TSH levels. Its effect has been demonstrated in combination with metformin and selenium compared to treatment without inositol [49,50][44][45]. The synthesis of thyroxine (T4) and triiodothyronine (T3) catalysed by thyroid peroxidase (TPO) in thyroid follicles is a very complex process involving ROS, notably, H2O2 (Figure 1) [51][46]. ROS are already essential in the initial stages of thyroid hormone production, during iodide oxidation [52][47]. Additionally, thyroid hormones perform a metabolic regulatory function by affecting mitochondrial activity [53][48]. Because of the reliance on ROS in its function, the thyroid is particularly exposed to oxidative damage [54][49]. Therefore, the antioxidant defence system of the thyroid must effectively regulate ROS production and scavenging [26,55][19][50].
Figure 1. Role of ROS in thyroid hormones synthesis. Based on [47,56][42][51]. Created with BioRender.com.(accessed on 26/08/2021) I—iodine, TPO—thyroid peroxidase, Tg—thyroglobulin, MIT—monoiodotyrosine, DIT—diiodotyrosine, T3—triiodothyronine, T4—thyroxine.

3. Biomarkers of Oxidative Stress in Thyroid Diseases

Enzymatic mechanisms of antioxidant defence constitute the internal system for maintaining ROS homeostasis (Figure 2). Superoxide dismutases (SOD1, SOD2, SOD3) are antioxidant enzymes, neutralising O2•− [17,57][9][52]. The key enzyme responsible for neutralising hydrogen peroxide is catalase (CAT), which converts it to water and oxygen [58][53]. Likewise, glutathione peroxidase (GPX) scavenges and detoxifies H2O2 [20][12]. Glutathione serves as an intracellular buffer against oxidation. In response to excessive ROS release, it forms an oxidised dimer structure by bridging two glutathione molecules. Glutathione reductase (GR) then restores the reduced form of glutathione, lowering its reactivity [59][54]. Measurement of antioxidant enzyme activity in serum makes it possible to evaluate the condition of the antioxidant defence system. Lower levels of this activity, compared to the control, may be a sign of inadequate defence against free radicals [60][55].
Figure 2. Free Radical Physiology. Created with BioRender.com. (accessed on 26 July 2021).
Biomarkers of oxidative stress also include prooxidant enzymes—NADPH oxidases (NOX), which are an endogenous source of ROS, especially in thyroid tissue [46][41]. Their increased activity is associated with elevated concentrations of reactive oxygen species in pathological conditions. Direct measurement of ROS concentrations may be a helpful marker in the evaluation of medical conditions, yet its utility may be limited given the short half-life of these molecules [15,18][7][10].
Malondialdehyde (MDA) is a product of lipid peroxidation by ROS. The marker can be used to evaluate oxidative damage and measure whole-body or tissue-specific oxidative stress [61,62][56][57]. Advanced glycation end products (AGE) are believed to be associated with the onset and progression of metabolic disorders, notably diabetes and obesity, due to their formation both through lipid peroxidation and glycoxidation reactions; that is, in response to an increased intake of simple carbohydrates [15,63][7][58]. Elevated levels are observed in ROS-damaged tissues, as the final product of peroxidation, making them markers of oxidative stress in the body [64][59]. Among DNA bases, guanine is the most easily oxidised, due to its relatively low redox potential. Its oxidised form (8-oxo-2′-deoxyguanosine) may therefore serve as a measurement of DNA damage in cells exposed to oxidative stress and in carcinogenesis. 8-oxo-2′-deoxyguanosine has mutagenic potential [9,65][6][60].
Total antioxidant capacity (TAC) is a parameter indicative of the body’s overall ability to neutralise oxidants. It takes into account all the antioxidants contained in bodily fluids, including exogenous and endogenous compounds [15][7]. In turn, total oxidant status (TOS) is based on the oxidation of ferrous ion to ferric ion in the presence of various oxidants. It reflects the oxidation state of bodily fluids, represented by the level of radicals [66][61]. Oxidative stress index (OSI) is a measure of oxidative stress, calculated as the ratio of total oxidant status to total antioxidant status and therefore represents the overall oxidation state of the body [67][62].
All the biomarkers employed in the determination of the role of oxidative stress in thyroid diseases in this review are listed in Table 1.
Table 1. Biomarkers of oxidative stress used in thyroid disease research [15][7].
Biomarkers Mechanism of Development, Role References
ROS Energy metabolism in mitochondria [68][63]
MDA, HNE Lipid peroxidation products [62][57]
AGE, ALE Protein oxidation products; Advanced peroxidation end products [64][59]
SOD, CAT, GPX, GR Antioxidant enzymes [62,68,69][57][63][64]
NOX, DUOX ROS-generating enzymes [70][65]
GSH/GSSG Reduced/oxygenated glutathione [ [64]69 ]
TAC, TOS Liczba moli utleniaczy zneutralizowanych przez jeden litr płynu ustrojowego; całkowity stan oksydacyjny;Number of moles of oxidants neutralised by one litre of body fluid; total oxidative status; [ [66]71[67] , 72 ]
ROS—reactive oxygen species, MDA—malondialdehyde, HNE—hydroxynonenal, AGE-advanced glycation end products, ALE—advanced lipoxidation end products, SOD—superoxide dismutase, CAT—catalase, GPX—glutathione peroxidase, GR—glutathione reductase, NOX—NADPH oxidases, DUOX—dual oxidase, GSH/GSSG—the reduced glutathione/oxidized glutathione ratio, TAC—total antioxidant capacity, TOS—total oxidant status.
ROS — reaktywne formy tlenu, MDA — dialdehyd malonowy, HNE — hydroksynonenal, produkty końcowe zaawansowanej glikacji AGE, produkty końcowe zaawansowanej lipooksydacji ALE, SOD — dysmutaza ponadtlenkowa, CAT — katalaza, GPX — peroksydaza glutationowa, GR — reduktaza glutationowa, NOX — oksydazy, DUOX – podwójna oksydaza, GSH/GSSG – obniżony stosunek glutation/utleniony glutation, TAC – całkowita zdolność antyoksydacyjna, TOS – całkowity stan utleniania.


  1. Jakubczyk, K.; Dec, K.; Kałduńska, J.; Kawczuga, D.; Kochman, J.; Janda, K. Reactive Oxygen Species—Sources, Functions, Oxidative Damage. Pol. Merkur. Lek. Organ Pol. Tow. Lek. 2020, 48, 124–127.
  2. Tan, B.L.; Norhaizan, M.E.; Liew, W.-P.-P. Nutrients and Oxidative Stress: Friend or Foe? Oxid. Med. Cell. Longev. 2018, 2018.
  3. Yang, S.; Lian, G. ROS and Diseases: Role in Metabolism and Energy Supply. Mol. Cell. Biochem. 2020, 467, 1–12.
  4. Shekhova, E. Mitochondrial Reactive Oxygen Species as Major Effectors of Antimicrobial Immunity. PLoS Pathog. 2020, 16, e1008470.
  5. Yun, H.R.; Jo, Y.H.; Kim, J.; Shin, Y.; Kim, S.S.; Choi, T.G. Roles of Autophagy in Oxidative Stress. Int. J. Mol. Sci. 2020, 21, 3289.
  6. Sies, H. Oxidative Stress: A Concept in Redox Biology and Medicine. Redox Biol. 2015, 4, 180–183.
  7. Di Marzo, N.; Chisci, E.; Giovannoni, R. The Role of Hydrogen Peroxide in Redox-Dependent Signaling: Homeostatic and Pathological Responses in Mammalian Cells. Cells 2018, 7, 156.
  8. Sies, H.; Berndt, C.; Jones, D.P. Oxidative Stress. Annu. Rev. Biochem. 2017, 86, 715–748.
  9. Filomeni, G.; De Zio, D.; Cecconi, F. Oxidative Stress and Autophagy: The Clash between Damage and Metabolic Needs. Cell Death Differ. 2015, 22, 377–388.
  10. Gu, Y.; Han, J.; Jiang, C.; Zhang, Y. Biomarkers, Oxidative Stress and Autophagy in Skin Aging. Ageing Res. Rev. 2020, 59, 101036.
  11. Vostrikova, S.M.; Grinev, A.B.; Gogvadze, V.G. Reactive Oxygen Species and Antioxidants in Carcinogenesis and Tumor Therapy. Biochem. Mosc. 2020, 85, 1254–1266.
  12. Mahdavi, A.; Naeini, A.A.; Najafi, M.; Maracy, M.; Ghazvini, M.A. Effect of Levetiracetam Drug on Antioxidant and Liver Enzymes in Epileptic Patients: Case-Control Study. Afr. Health Sci. 2020, 20, 984–990.
  13. Jakubczyk, K.; Kałduńska, J.; Dec, K.; Kawczuga, D.; Janda, K. Antioxidant Properties of Small-Molecule Non-Enzymatic Compounds. Pol. Merkur. Lek. Organ Pol. Tow. Lek. 2020, 48, 128–132.
  14. Kowalska, K.; Brodowski, J.; Pokorska-Niewiada, K.; Szczuko, M. The Change in the Content of Nutrients in Diets Eliminating Products of Animal Origin in Comparison to a Regular Diet from the Area of Middle-Eastern Europe. Nutrients 2020, 12, 2986.
  15. Marrocco, I.; Altieri, F.; Peluso, I. Measurement and Clinical Significance of Biomarkers of Oxidative Stress in Humans. Oxid. Med. Cell. Longev. 2017, 2017, 6501046.
  16. Sies, H.; Jones, D.P. Reactive Oxygen Species (ROS) as Pleiotropic Physiological Signalling Agents. Nat. Rev. Mol. Cell Biol. 2020, 21, 363–383.
  17. Fukai, T.; Ushio-Fukai, M. Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis. Cells 2020, 9, 1849.
  18. Kim, Y.-M.; Kim, S.-J.; Tatsunami, R.; Yamamura, H.; Fukai, T.; Ushio-Fukai, M. ROS-Induced ROS Release Orchestrated by Nox4, Nox2, and Mitochondria in VEGF Signaling and Angiogenesis. Am. J. Physiol. Cell Physiol. 2017, 312, C749–C764.
  19. Aldosari, S.; Awad, M.; Harrington, E.O.; Sellke, F.W.; Abid, M.R. Subcellular Reactive Oxygen Species (ROS) in Cardiovascular Pathophysiology. Antioxid. Basel Switz. 2018, 7, 14.
  20. Irazabal, M.V.; Torres, V.E. Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease. Cells 2020, 9, 1342.
  21. Garmendia Madariaga, A.; Santos Palacios, S.; Guillén-Grima, F.; Galofré, J.C. The Incidence and Prevalence of Thyroid Dysfunction in Europe: A Meta-Analysis. J. Clin. Endocrinol. Metab. 2014, 99, 923–931.
  22. Canaris, G.J.; Manowitz, N.R.; Mayor, G.; Ridgway, E.C. The Colorado Thyroid Disease Prevalence Study. Arch. Intern. Med. 2000, 160, 526–534.
  23. Kasagi, K.; Takahashi, N.; Inoue, G.; Honda, T.; Kawachi, Y.; Izumi, Y. Thyroid Function in Japanese Adults as Assessed by a General Health Checkup System in Relation with Thyroid-Related Antibodies and Other Clinical Parameters. Thyroid 2009, 19, 937–944.
  24. Empson, M.; Flood, V.; Ma, G.; Eastman, C.J.; Mitchell, P. Prevalence of Thyroid Disease in an Older Australian Population. Intern. Med. J. 2007, 37, 448–455.
  25. Rostami, R.; Aghasi, M.R.; Mohammadi, A.; Nourooz-Zadeh, J. Enhanced Oxidative Stress in Hashimoto’s Thyroiditis: Inter-Relationships to Biomarkers of Thyroid Function. Clin. Biochem. 2013, 46, 308–312.
  26. Ameziane El Hassani, R.; Buffet, C.; Leboulleux, S.; Dupuy, C. Oxidative Stress in Thyroid Carcinomas: Biological and Clinical Significance. Endocr. Relat. Cancer 2019, 26, R131–R143.
  27. Fahim, Y.A.; Sharaf, N.E.; Hasani, I.W.; Ragab, E.A.; Abdelhakim, H.K. Assessment of Thyroid Function and Oxidative Stress State in Foundry Workers Exposed to Lead. J. Health Pollut. 2020, 10, 200903.
  28. Lassoued, S.; Mseddi, M.; Mnif, F.; Abid, M.; Guermazi, F.; Masmoudi, H.; El Feki, A.; Attia, H. A Comparative Study of the Oxidative Profile in Graves’ Disease, Hashimoto’s Thyroiditis, and Papillary Thyroid Cancer. Biol. Trace Elem. Res. 2010, 138, 107–115.
  29. Mehran, L.; Amouzegar, A.; Rahimabad, P.K.; Tohidi, M.; Tahmasebinejad, Z.; Azizi, F. Thyroid Function and Metabolic Syndrome: A Population-Based Thyroid Study. Horm. Metab. Res. 2017, 49, 192–200.
  30. Du, F.-M.; Kuang, H.-Y.; Duan, B.-H.; Liu, D.-N.; Yu, X.-Y. Effects of Thyroid Hormone and Depression on Common Components of Central Obesity. J. Int. Med. Res. 2019, 47, 3040–3049.
  31. Song, R.-H.; Wang, B.; Yao, Q.-M.; Li, Q.; Jia, X.; Zhang, J.-A. The Impact of Obesity on Thyroid Autoimmunity and Dysfunction: A Systematic Review and Meta-Analysis. Front. Immunol. 2019, 10, 2349.
  32. Heinonen, S.; Buzkova, J.; Muniandy, M.; Kaksonen, R.; Ollikainen, M.; Ismail, K.; Hakkarainen, A.; Lundbom, J.; Lundbom, N.; Vuolteenaho, K.; et al. Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity. Diabetes 2015, 64, 3135–3145.
  33. Parra, M.D.; Martínez de Morentin, B.E.; Martínez, J.A. Postprandial Insulin Response and Mitochondrial Oxidation in Obese Men Nutritionally Treated to Lose Weight. Eur. J. Clin. Nutr. 2005, 59, 334–340.
  34. Anderson, E.J.; Lustig, M.E.; Boyle, K.E.; Woodlief, T.L.; Kane, D.A.; Lin, C.-T.; Price, J.W.; Kang, L.; Rabinovitch, P.S.; Szeto, H.H.; et al. Mitochondrial H2O2 Emission and Cellular Redox State Link Excess Fat Intake to Insulin Resistance in Both Rodents and Humans. J. Clin. Investig. 2009, 119, 573–581.
  35. Saraf-Bank, S.; Ahmadi, A.; Paknahad, Z.; Maracy, M.; Nourian, M. Effects of Curcumin Supplementation on Markers of Inflammation and Oxidative Stress among Healthy Overweight and Obese Girl Adolescents: A Randomized Placebo-Controlled Clinical Trial. Phytother. Res. 2019, 33, 2015–2022.
  36. Yin, X.; Lanza, I.R.; Swain, J.M.; Sarr, M.G.; Nair, K.S.; Jensen, M.D. Adipocyte Mitochondrial Function Is Reduced in Human Obesity Independent of Fat Cell Size. J. Clin. Endocrinol. Metab. 2014, 99, E209–E216.
  37. Fischer, B.; Schöttl, T.; Schempp, C.; Fromme, T.; Hauner, H.; Klingenspor, M.; Skurk, T. Inverse Relationship between Body Mass Index and Mitochondrial Oxidative Phosphorylation Capacity in Human Subcutaneous Adipocytes. Am. J. Physiol. Endocrinol. Metab. 2015, 309, E380–E387.
  38. Christe, M.; Hirzel, E.; Lindinger, A.; Kern, B.; von Flüe, M.; Peterli, R.; Peters, T.; Eberle, A.N.; Lindinger, P.W. Obesity Affects Mitochondrial Citrate Synthase in Human Omental Adipose Tissue. ISRN Obes. 2013, 2013, 826027.
  39. Schmid, D.; Ricci, C.; Behrens, G.; Leitzmann, M.F. Adiposity and Risk of Thyroid Cancer: A Systematic Review and Meta-Analysis. Obes. Rev. Off. J. Int. Assoc. Study Obes. 2015, 16, 1042–1054.
  40. Schieber, M.; Chandel, N.S. ROS Function in Redox Signaling and Oxidative Stress. Curr. Biol. CB 2014, 24, R453–R462.
  41. Sies, H. Hydrogen Peroxide as a Central Redox Signaling Molecule in Physiological Oxidative Stress: Oxidative Eustress. Redox Biol. 2017, 11, 613–619.
  42. Ameziane-El-Hassani, R.; Schlumberger, M.; Dupuy, C. NADPH Oxidases: New Actors in Thyroid Cancer? Nat. Rev. Endocrinol. 2016, 12, 485–494.
  43. Cardoso, L.C.; Martins, D.C.; Figueiredo, M.D.; Rosenthal, D.; Vaisman, M.; Violante, A.H.; Carvalho, D.P. Ca2+/Nicotinamide Adenine Dinucleotide Phosphate-Dependent H2O2 Generation Is Inhibited by Iodide in Human Thyroids. J. Clin. Endocrinol. Metab. 2001, 86, 4339–4343.
  44. Dupuy, C.; Virion, A.; Ohayon, R.; Kaniewski, J.; Dème, D.; Pommier, J. Mechanism of Hydrogen Peroxide Formation Catalyzed by NADPH Oxidase in Thyroid Plasma Membrane. J. Biol. Chem. 1991, 266, 3739–3743.
  45. Piras, C.; Pibiri, M.; Leoni, V.P.; Balsamo, A.; Tronci, L.; Arisci, N.; Mariotti, S.; Atzori, L. Analysis of Metabolomics Profile in Hypothyroid Patients before and after Thyroid Hormone Replacement. J. Endocrinol. Investig. 2021, 44, 1309–1319.
  46. Ohye, H.; Sugawara, M. Dual Oxidase, Hydrogen Peroxide and Thyroid Diseases. Exp. Biol. Med. Maywood NJ 2010, 235, 424–433.
  47. Benvenga, S.; Nordio, M.; Laganà, A.S.; Unfer, V. The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management. Front. Endocrinol. 2021, 12, 662582.
  48. Grasberger, H.; Van Sande, J.; Hag-Dahood Mahameed, A.; Tenenbaum-Rakover, Y.; Refetoff, S. A Familial Thyrotropin (TSH) Receptor Mutation Provides in Vivo Evidence That the Inositol Phosphates/Ca2+ Cascade Mediates TSH Action on Thyroid Hormone Synthesis. J. Clin. Endocrinol. Metab. 2007, 92, 2816–2820.
  49. Morgante, G.; Musacchio, M.C.; Orvieto, R.; Massaro, M.G.; De Leo, V. Alterations in Thyroid Function among the Different Polycystic Ovary Syndrome Phenotypes. Gynecol. Endocrinol. 2013, 29, 967–969.
  50. Pace, C.; Tumino, D.; Russo, M.; Le Moli, R.; Naselli, A.; Borzì, G.; Malandrino, P.; Frasca, F. Role of Selenium and Myo-Inositol Supplementation on Autoimmune Thyroiditis Progression. Endocr. J. 2020, 67, 1093–1098.
  51. Thanas, C.; Ziros, P.G.; Chartoumpekis, D.V.; Renaud, C.O.; Sykiotis, G.P. The Keap1/Nrf2 Signaling Pathway in the Thyroid—2020 Update. Antioxidants 2020, 9, 1082.
  52. Massart, C.; Hoste, C.; Virion, A.; Ruf, J.; Dumont, J.E.; Van Sande, J. Cell Biology of H2O2 Generation in the Thyroid: Investigation of the Control of Dual Oxidases (DUOX) Activity in Intact Ex Vivo Thyroid Tissue and Cell Lines. Mol. Cell. Endocrinol. 2011, 343, 32–44.
  53. Venditti, P.; Puca, A.; Di Meo, S. Effects of Thyroid State on H2O2 Production by Rat Heart Mitochondria: Sites of Production with Complex I- and Complex II-Linked Substrates. Horm. Metab. Res. 2003, 35, 55–61.
  54. Paunkov, A.; Chartoumpekis, D.V.; Ziros, P.G.; Chondrogianni, N.; Kensler, T.W.; Sykiotis, G.P. Impact of Antioxidant Natural Compounds on the Thyroid Gland and Implication of the Keap1/Nrf2 Signaling Pathway. Curr. Pharm. Des. 2019, 25, 1828–1846.
  55. Poncin, S.; Gérard, A.-C.; Boucquey, M.; Senou, M.; Calderon, P.B.; Knoops, B.; Lengelé, B.; Many, M.-C.; Colin, I.M. Oxidative Stress in the Thyroid Gland: From Harmlessness to Hazard Depending on the Iodine Content. Endocrinology 2008, 149, 424–433.
  56. Szanto, I.; Pusztaszeri, M.; Mavromati, M. H2O2 Metabolism in Normal Thyroid Cells and in Thyroid Tumorigenesis: Focus on NADPH Oxidases. Antioxidants 2019, 8, 126.
  57. Eleutherio, E.C.A.; Magalhães, R.S.S.; de Araújo Brasil, A.; Neto, J.R.M.; de Holanda Paranhos, L. SOD1, More than Just an Antioxidant. Arch. Biochem. Biophys. 2021, 697.
  58. Sepasi Tehrani, H.; Moosavi-Movahedi, A.A. Catalase and Its Mysteries. Prog. Biophys. Mol. Biol. 2018, 140, 5–12.
  59. Couto, N.; Wood, J.; Barber, J. The Role of Glutathione Reductase and Related Enzymes on Cellular Redox Homoeostasis Network. Free Radic. Biol. Med. 2016, 95, 27–42.
  60. Metere, A.; Frezzotti, F.; Graves, C.E.; Vergine, M.; De Luca, A.; Pietraforte, D.; Giacomelli, L. A Possible Role for Selenoprotein Glutathione Peroxidase (GPx1) and Thioredoxin Reductases (TrxR1) in Thyroid Cancer: Our Experience in Thyroid Surgery. Cancer Cell Int. 2018, 18, 7.
  61. Torun, A.N.; Kulaksizoglu, S.; Kulaksizoglu, M.; Pamuk, B.O.; Isbilen, E.; Tutuncu, N.B. Serum Total Antioxidant Status and Lipid Peroxidation Marker Malondialdehyde Levels in Overt and Subclinical Hypothyroidism. Clin. Endocrinol. 2009, 70, 469–474.
  62. Erdamar, H.; Cimen, B.; Gülcemal, H.; Saraymen, R.; Yerer, B.; Demirci, H. Increased Lipid Peroxidation and Impaired Enzymatic Antioxidant Defense Mechanism in Thyroid Tissue with Multinodular Goiter and Papillary Carcinoma. Clin. Biochem. 2010, 43, 650–654.
  63. Loomis, S.J.; Chen, Y.; Sacks, D.B.; Christenson, E.S.; Christenson, R.H.; Rebholz, C.M.; Selvin, E. Cross-Sectional Analysis of AGE-CML, SRAGE, and EsRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort. Clin. Chem. 2017, 63, 980–989.
  64. Ruggeri, R.M.; Giovinazzo, S.; Barbalace, M.C.; Cristani, M.; Alibrandi, A.; Vicchio, T.M.; Giuffrida, G.; Aguennouz, M.H.; Malaguti, M.; Angeloni, C.; et al. Influence of Dietary Habits on Oxidative Stress Markers in Hashimoto’s Thyroiditis. Thyroid Off. J. Am. Thyroid Assoc. 2021, 31, 96–105.
  65. Kasai, H. Analysis of a Form of Oxidative DNA Damage, 8-Hydroxy-2′-Deoxyguanosine, as a Marker of Cellular Oxidative Stress during Carcinogenesis. Mutat. Res. Mutat. Res. 1997, 387, 147–163.
  66. Rovcanin, B.R.; Gopcevic, K.R.; Kekic, D.L.; Zivaljevic, V.R.; Diklic, A.D.; Paunovic, I.R. Papillary Thyroid Carcinoma: A Malignant Tumor with Increased Antioxidant Defense Capacity. Tohoku J. Exp. Med. 2016, 240, 101–111.
  67. Ates, I.; Arikan, M.F.; Altay, M.; Yilmaz, F.M.; Yilmaz, N.; Berker, D.; Guler, S. The Effect of Oxidative Stress on the Progression of Hashimoto’s Thyroiditis. Arch. Physiol. Biochem. 2018, 124, 351–356.
  68. Bednarek, J.; Wysocki, H.; Sowinski, J. Oxidation Products and Antioxidant Markers in Plasma of Patients with Graves’ Disease and Toxic Multinodular Goiter: Effect of Methimazole Treatment. Free Radic. Res. 2004, 38, 659–664.
  69. Rostami, R.; Nourooz-Zadeh, S.; Mohammadi, A.; Khalkhali, H.R.; Ferns, G.; Nourooz-Zadeh, J. Serum Selenium Status and Its Interrelationship with Serum Biomarkers of Thyroid Function and Antioxidant Defense in Hashimoto’s Thyroiditis. Antioxidants 2020, 9, 1070.
  70. Fortunato, R.S.; Braga, W.M.O.; Ortenzi, V.H.; Rodrigues, D.C.; Andrade, B.M.; Miranda-Alves, L.; Rondinelli, E.; Dupuy, C.; Ferreira, A.C.F.; Carvalho, D.P. Sexual Dimorphism of Thyroid Reactive Oxygen Species Production Due to Higher NADPH Oxidase 4 Expression in Female Thyroid Glands. Thyroid Off. J. Am. Thyroid Assoc. 2013, 23, 111–119.
  71. Faam, B.; Ghadiri, A.A.; Ghaffari, M.A.; Totonchi, M.; Khorsandi, L. Comparing Oxidative Stress Status Among Iranian Males and Females with Malignant and Non-Malignant Thyroid Nodules. Int. J. Endocrinol. Metab. 2021, 19, e105669.
  72. Ates, I.; Yilmaz, F.M.; Altay, M.; Yilmaz, N.; Berker, D.; Güler, S. The Relationship between Oxidative Stress and Autoimmunity in Hashimoto’s Thyroiditis. Eur. J. Endocrinol. 2015, 173, 791–799.
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