A Study of Selenomethionine and Myo-inositol(SOLOWAYS_TM) in Patients With Autoimmune Thyroiditis Carrying the DIO2 Thr92Ala Polymorphism

Rationale

• The DIO2 gene encodes the type II iodothyronine deiodinase, which converts T4 (thyroxine) to the more active T3 (triiodothyronine) in peripheral tissues.
• The Thr92Ala (rs225014) polymorphism may reduce enzyme activity, potentially leading to lower tissue T3 levels, even in patients with normal or slightly elevated T4 and TSH.
• Selenium (as selenomethionine) supports the function of various selenoproteins, including deiodinases, and has been reported to reduce anti-thyroid antibody levels (particularly anti-TPO).
• Myo-inositol has shown promise in modulating autoimmune and metabolic processes in thyroid disorders, possibly improving tissue sensitivity to thyroid hormones and reducing autoimmune inflammation.
• A genotype-focused approach may reveal whether individuals carrying the DIO2 Thr92Ala variant derive a more substantial benefit from combined supplementation than those without the variant. 2. Study Goals
• Primary Goal: To assess changes in TSH levels and the fT3/fT4 ratio over 12 weeks of combined selenomethionine and myo-inositol supplementation.
• Secondary Goals:

• To evaluate changes in thyroid autoantibody titers (anti-TPO, anti-Tg).
• To assess thyroid ultrasound findings (vascularization, gland volume).
• To measure improvements in patient-reported symptoms and quality of life using standardized questionnaires.
• To determine the safety and tolerability of the combined intervention.

Inclusion criteria

• Adults aged 18-65 years with a clinical diagnosis of autoimmune thyroiditis (elevated anti- TPO and/or anti-Tg).
• TSH range consistent with subclinical hypothyroidism (e.g., TSH 4.5-10 mIU/L) or euthyroid status with AIT; patients on stable levothyroxine therapy are eligible if dose was unchanged for at least 6 weeks.
• Willingness to undergo genotyping for the DIO2 Thr92Ala variant. Confirmation of the Thr92Ala variant (homozygous or heterozygous) for Cohort A; absence of this variant for Cohort B.
• Ability to provide informed consent and comply with study procedures.

Exclusion criteria

• Overt hypothyroidism with TSH >10 mIU/L requiring immediate treatment adjustment.
• Significant comorbidities (e.g., uncompensated heart failure, severe renal or hepatic dysfunction, uncontrolled diabetes).
• Pregnancy or lactation (given potential changes in thyroid requirements and supplement safety considerations).
• Known hypersensitivity to selenium or inositol supplements.
• Severe psychiatric disorder interfering with protocol adherence.
• Concurrent use of high-dose selenium (>50 µg/day) or other thyroid-influencing nutraceuticals that cannot be discontinued prior to study entry.