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].

Oxidative stress is an effect of redox imbalance between reactive oxygen species and antioxidant defence ^[6][7][9,15]. It may be caused both by the excessive production of ROS and by an inefficient antioxidant system, resulting in molecular damage ^[8][16]. Additionally, ROS generation in different subcellular compartments likely involves a positive feedback mechanism, creating a vicious circle of pathological conditions related to oxidative stress ^[9][10][11][17,18,19]. Redox homeostasis requires an equilibrium of ROS production and scavenging ^[12][20]. Even though the concept of oxidative stress was introduced in the 1980s, its definition and scope of research have been continually elaborated and expanded ^[13][6].

Thyroid diseases are a common health problem worldwide, especially among women. The occurrence of subclinical thyroid disorders, which often remain undiagnosed, is also significant ^{[14][15][16][17]}[21,22,23,24]. Thyroid diseases are increasingly linked to oxidative stress ^{[18][19][20][21]}[25,26,27,28]. It has been shown that thyroid dysfunction can co-occur with metabolic disorders, including obesity ^[22][23][24][29,30,31]. Obesity is a metabolic disease involving mitochondrial dysfunction and chronic oxidative stress, as in several metabolic disorders ^{[25][26][27][28][29][30][31]}[32,33,34,35,36,37,38]. 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 ^[23][24][32][30,31,39]. 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 ^[12][20]. The process alters redox signalling ^[9][17]. Accumulation of excessive concentrations of H₂O₂ activates thiolate anion (Cys-S-) oxidation pathways. This is an irreversible process, resulting in permanent protein damage ^[33][40]. Antioxidant systems serve a protective function, preventing intracellular accumulation of ROS by reversing the modification of cysteine residues ^[12][20]. 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 ^[34][7]. Excessive amounts of ROS at the subcellular level activates pathways leading to damage in particularly susceptible cell structures or apoptosis ^[33][40]. In turn, at low physiological levels, ROS play a signalling role, essential for normal cellular processes ^[35][36][8,41]. 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 ^[37][38][39][42,43,44]. 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 ^{[40][41][42][43]}[45,46,47,48]. 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 ^[40][43][45,48]. 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 ^[44][45][49,50]. 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) ^[46][51]. ROS are already essential in the initial stages of thyroid hormone production, during iodide oxidation ^[47][52]. Additionally, thyroid hormones perform a metabolic regulatory function by affecting mitochondrial activity ^[48][53]. Because of the reliance on ROS in its function, the thyroid is particularly exposed to oxidative damage ^[49][54]. Therefore, the antioxidant defence system of the thyroid must effectively regulate ROS production and scavenging ^[19][50][26,55].