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Myo-Inositol and Selenium Restore Euthyroid State

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Myo-Inositol and Selenium Restore Euthyroid State Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2017; 21 (2 Suppl): 51-59 Myo-inositol plus selenium supplementation restores euthyroid state in Hashimoto’s patients with subclinical hypothyroidism M. NORDIO, S. BASCIANI Department of Experimental Medicine, University of Rome “Sapienza”, Rome, Italy Abstract. – OBJECTIVE : Clinical evidence thyroglobulin (TgAb) and anti-thyroid peroxi - suggests that oral supplementation with myo-in - dase (TPOAb ) are typical features of AIT . In ositol (MI) and selenium (Se) is useful in the such pathologies, among which Hashimoto’s thy - treatment of autoimmune thyroiditis. The pur - pose of this study was to highlight the positive roiditis (HT) is the most representative, thyroid response of Hashimoto’s patients with subclini - gland gets progressively underactive , due to cell cal hypothyroidism (SH) treated with MI and Se and antibody-mediated autoimmune processes 2. (MI-Se) in restoring a normal thyroid function. A mild thyroid failure is called subclinical hy - PATIENTS AND METHODS: A total of 168 pa - pothyroidism (SH), and usually is balanced by a tients with Hashimoto’s thyroiditis (HT) having slight TSH level increase , approximately be - Thyroid Stimulating Hormone (TSH) levels be - tween 3 and 6 µIU/ml were randomized into 2 tween 3-6 µIU/ml . According to the American groups: one receiving MI-Se and the other one Thyroid Association’s (ATA’s) guidelines, the Se alone. normal range for TSH values, with an upper limit RESULTS: TSH, anti-thyroid peroxidase of 4.12 µIU/ml is largely based on National (TPOAb) and anti-thyroglobulin (TgAb) levels Health and Nutrition Examination Survey were significantly decreased in patients treated (NHANES) III data, but it has not been univer - with combined MI-Se after six months of treat - sally accepted. In fact, some have proposed that ment. Also, a significant free serum T4 increase was observed in MI-Se group, along with an the upper normal TSH values should be either 3 amelioration of patients’ quality of life. 2.5 or 3.0 . TSH , a glycoprotein secreted by the CONCLUSIONS: The administration of MI-Se hypophysis, regulates the hypothalamic-pitu - is significantly effective in decreasing TSH, itary-thyroid axis by harmonizing the release of TPOAb and TgAb levels, as well as in enhancing thyroid hormones 4. It plays several key physio - thyroid hormones and personal wellbeing. Such logical roles, from the promotion of thyroid ep - treatment restored euthyroidism in patients di - 5 agnosed with autoimmune thyroiditis. ithelial differentiation and growth , iodide uptake and transport 6, to protection of thyroid cells from Key Words: apoptosis 7. Particularly, on thyroid follicular Myo-inositol, Selenium, Autoimmune thyroiditis, cells, TSH binds to the TSH receptor, stimulating TSH, TPOAb, TgAb, Hashimoto's thyroiditis, Subclinical cell growth and differentiation, in addition to hypothyroidism . thyroid hormone synthesis. This binding with TSH receptors activates adenylyl cyclase, lead - ing to an increase of intracellular cyclic AMP and protein Kinase A phosphorylation, and also Introduction to an activation of cytosolic and nuclear target proteins. At high doses, TSH stimulates the Chronic autoimmune thyroiditis (AIT) is one phospholipase C-dependent inositol phosphate of the most common autoimmune diseases in io - Ca 2+ /diacyglycerol pathway, resulting in a boost 8 dine-sufficient areas , affecting more than 10% of of hydrogen peroxide (H 2O2) generation . Be - females and 2% of males in the overall popula - sides, it has been shown that impairment of TSH tion. Although this illness may often occur in signal transduction leads not only to thyroid dis - children and teenagers, it mainly affects 30-50 orders such as hypothyroidism and hyperthy - years old people 1. Elevated Thyroid Stimulating roidism , but also to the proliferation and differ - Hormone (TSH) and autoantibodies such as anti- entiation of human thyroid carcinoma cells 9. Corresponding Author: Maurizio Nordio, MD; e-mail: [email protected] 51 M. Nordio, S. Basciani Currently, a specific treatment for AIT has not vestigate the efficacy of a combined administra - been found yet, however , various studies have tion of MI and Se in AIT to evaluate whether this demonstrated that L-thyroxine (L-T4) 10 and sele - treatment could restore euthyroid state and im - nium (Se) 11 may moderately lower antibodies prove personal well being in HT patients. serum concentrations in HT patients. Particular - ly, in a randomized, placebo-controlled prospec - tive study the administration of Se plus LT4 was Patients and Methods beneficial to AIT patients, reducing serum TPOAb and TSH levels 12 , although L-T4 effica - A total of 168 outpatients (mean age 40 .85 ± cy is quite controversial in patients with already 8. 5 years) with HT were enrolled in this prospec - low TSH levels 13 . Mazokopakis et al 14 have tive randomized controlled trial (RCT) from shown that Se significantly decreased the serum March 2015 to February 2016 . Each participant TPOAb concentrations after a 12 months treat - filled in the informed consent. This study was ment period. Another study demonstrated that 12 approved by the ethics committee of the Italian months of 80 µg sodium selenite administration Society of Phytotherapy and Supplements in Ob - to AIT patients reduced TPOAb and TgAb con - stetrics and Gynecology (SIFIOG). Inclusion cri - centrations, whereas TSH and free thyroxine teria were: age range 22-6 2, TSH levels between 15 (fT 4) levels were unvaried . Likewise, 200 µg 3- 6 µIU/ml , elevated serum TPOAb and/or sodium selenite per day were able to decrease TgAb, normal fT 4 level (0.6-1.8 ng/dl ) and free serum thyroid TPOAb autoantibodies levels after triiodothyronine (fT 3) ( 2.0-3.5 pg/ml ). Exclusion 3 months of treatment in autoimmune thyroid pa - criteria were: debilitating illnesses (e.g. depres - tients 16 . Furthermore, in the same clinical trial, sion, psychosis, severe hepatic or renal failure); the Se effect was evaluated in improving the pa - malabsorption disorders (atrophic gastritis, celiac tients’ wellbeing, as subjects with AIT normally disease); adjuvant treatment with vitamins or have impaired health-related quality of life 16 . trace elements. The primary outcome was the re - Se is an essential trace element for humans ; se - duction of serum TSH levels. The secondary out - lenium-dependent enzymes exert antioxidant and comes were the restoration of TPOAb, TgAb, fT 3 17 anti-inflammatory properties . It has a relevant and fT 4 hormone concentrations as well as the impact on immune function 17 ; de facto , it has quality of life evaluation. been shown to reduce the inflammatory status in Patients were randomized 1:1 into 2 groups: patients with AIT 16 . Se-dependent enzymes, such 84 subjects (control group :A)including 10 men as Glutathione Peroxidase (GPx), substantially and 74 women, and 84 subjects (experimental have the ability to diminish hydrogen peroxides, group: B) , with 9 men and 75 women. The cal - lipid, and phospholipid hydroperoxides ; in this culation of the sample size determined that a way, they limit the propagation of free radicals minimum of 52 patients were required in each and reactive oxygen species, resulting in a reduc - group to have an acceptable statistical power . tion of inflammatory prostaglandins (PGs) and At baseline , both groups had similar values for 18,19 leukotrienes . age, and TSH, TPOAb , TgAb , fT 3 and fT 4 hor - In a previous study 20 from our laboratory , the mone levels. Controls (group A) were given co-treatment with L-selenomethionine plus myo- 16.6 mg L-selenomethionine (corresponding to inositol (MI) demonstrated a beneficial effect on 83 µg Se ) in tablets, and patients in group B SH, restoring a euthyroid state and reducing both were given tablets containing 600 mg MI plus TPOAb and TSH levels, bringing them closer to 16.6 mg L-selenomethionine (= 83 µg Se ) physiological levels . (Tiroxil ®, LO.LI. Pharma Srl, Rome, Italy ). Pa - MI is a carbocyclic polyol precursor of phos - tients were asked to take the supplement with phoinositide synthesis; it is involved in cell sig - water about 2 hours before or after the meal , for naling 21 and, precisely, as a second messenger six months. Subjects were treated daily by oral regulating the activities of several hormones route and asked to bring back the empty boxes , such as TSH, follicle-stimulatin g hormone used for the treatment , at the following sched - (FSH) and insulin 22 . Indeed, in TSH signal cas - uled medical visits . Also, a questionnaire to cade, inositol regulates hydrogen peroxide-medi - evaluate the level of subjective symptomatology ated iodination 23 . (SS), due to the thyroid inflammation process, Based on this clinical evidence and our previ - was filled in by each patient at the beginning ous preliminary data , we decided to further in - and the end of the study. 52 Myo-inositol and selenium restore euthyroid state Laboratory and Technical Investigations The flow rate was fixed to 1.2 ml/min and results From the 171 patients selected, 1 68 agreed to were analyzed by an MS 5973 Network Series enter the study . Three of them were excluded detector in SIM mode. when they got pregnant during the recruiting pe - At enrolment and after 6 months the SS was riod. evaluated using a questionnaire 25 , which includes Blood samples were drawn from each patient 7 questions ranging from the level of pain to the and serum TSH, fT 3, fT 4, TPOAb, and TgAb lev - degree of discomfort during swallowing, with an els were measured at baseline and the end of the arbitrary scale between 0 = no symptoms and 4 = 6-month period. The concentrations of fT 3, fT 4 very important symptoms . and TSH were measured by an enzyme immuno - metric assay (Byk-Sangtec Dietzenbach, Ger - Statistical Analysis many). Plasma total TPOAb and TgAb concen - Data were processed using Graph Pad Prism, trations were measured by a commercial enzyme version 6.0f (Mac, San Diego, CA, USA) and are luminescence assay (Byk-Sangtec, Dietzenbach, indicated as mean values ± standard deviation Germany).
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