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Review
. 2021 May 10:12:662582.
doi: 10.3389/fendo.2021.662582. eCollection 2021.

The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management

Salvatore Benvenga  1   2 , Maurizio Nordio  2   3 , Antonio Simone Laganà  2   4 , Vittorio Unfer  2   5
Affiliations
Review

The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management

Salvatore Benvenga et al. Front Endocrinol (Lausanne). .

Abstract

Myo-Inositol (MYO) is the most abundant stereoisomer of inositols' family, cyclic polyols with 6 hydroxyl groups. Myo-Inositol has a relevant role in thyroid function and autoimmune diseases, as a precursor of phosphoinositides that takes part in the phosphatidylinositol (PI) signal transduction pathway. Among phosphoinositides, phosphatidylinositol 4,5- bisphosphate (PIP2) is the precursor of inositol triphosphates (IP3), second messenger of several hormones including thyroid-stimulating hormone (TSH). As a second messenger in the phospholipase C (PLC)-dependent inositol phosphate Ca2+/DAG pathway, Myo-Inositol is essential to produce H2O2 required for the synthesis of thyroid hormones. Consequently, depletion of Myo-Inositol or impaired inositol dependent TSH signaling pathway may predispose to the development of some thyroid diseases, such as hypothyroidism. Many clinical studies have shown that after treatment with Myo-Inositol plus Selenium (MYO+Se), TSH levels significantly decreased in patients with subclinical hypothyroidism with or without autoimmune thyroiditis. The TSH reduction was accompanied by a decline of antithyroid autoantibodies. Moreover, Myo-Inositol supplementation seemed to be involved also in the management of thyroidal benign nodules, with a possible effect in the size reduction. This review proposes a summary of the role of inositol, especially of Myo-Inositol, in the thyroidal physiology and its contribution on the management of some thyroid diseases.

Keywords: TSH; myo-inositol; subclinical hypothyroidism; thyroid dysfunctions; thyroid hormones.

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Conflict of interest statement

VU is an employee at Lo.Li Pharma s.r.l., Rome (Italy). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
T4 (or T3) synthesis from Tg in thyroid gland. DUOX, dual oxidase; H2O2, hydrogen peroxide; I-, iodine; NIS, sodium/iodide symporter; T3, triiodothyronine; T4, thyroxine; TG, thyroglobulin. Reproduced with the permission from “The structure of human thyroglobulin.” Coscia F. et al., Nature 578.7796 (2020): 627-630 (License No 4998080013478).
Figure 2
Figure 2
Principal pathways active by the TSH-TSHR binding. AC, adenylate cyclase; AKT, protein kinase B; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; Gαs/Gqs, G protein; GTP, guanosine triphosphate; IP3, inositol triphosphate; mTOR, protein kinase (mammalian target of rapamicin); PDE, phosphoesterase; PIP2, phosphatidylinositol 4,5- biphosphate; PKA, protein kinase A; PLC, phospholipase C; TSHR, TSH Receptor; TSH, thyroid stimulating hormone. Reproduced with the permission from Benvenga et al. (23) (License No 4997560949993).
Figure 3
Figure 3
Role of Myo-Inositol in physiology of thyroid. Ca, calcium; cAMP, cyclic adenosine monophosphate; DAG, diacylglycerol; DUOXA2, dual oxidase A 2; ER, endoplasmic reticulum; H2O2, hydrogen peroxide; I-, iodine; IP3, inositol triphosphate; MI, myo-inositol; MIT, monoiodotyrosine; NAPD+/NADPH, nicotinamide adenine dinucleotide phosphate; O2, oxygen; PDS, pendrin; PKA, protein kinase A; PKC, protein kinase C; PLC, phospholipase C; PTDIns, phosphatidylinositol; TG, thyroglobulin; TSH, thyroid stimulating hormone; TSHR, TSH Receptor; TPO, thyreoperoxidase.
See this image and copyright information in PMC

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