Myo-inositol and Selenium in Indeterminate Thyroid Nodules (TIR3a) (MYOSEL)

Use of Myo-inositol and Selenium in Patients with Indeterminate Thyroid Nodules (TIR3A)

Thyroid nodules present a variable risk of malignancy depending on the cytological result obtained from the ultrasound-assisted thyroid fine needle aspiration biopsy. According to the Italian Cytology classification SIAPEC-IAP 2014, the TIR3A nodules are indeterminate nodules with a risk of malignancy lower than 10%. Clinical and instrumental follow-up is recommended in these cases, including repetition of the fine needle aspiration.

A study have demonstrate the effect of a six-month treatment with a supplement containing myo-inositol and selenium on the size and elasticity of benign thyroid nodules.

Our hypothesis is that the use of this supplement can determine a reduction in the size and consistency of the nodule assessed through ultrasound and elastosonography also in cytologically indeterminate (TIR3A) nodules and that treatment can reduce the cellular proliferation of these nodules assessed by immunocytochemistry.

Therefore, we design a prospective randomized pilot study to assess efficacy and safety of myo-inositol and selenium in TIR3a thyroid nosules, comparing treated and untreated patients.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Nodule
• Intervention / Treatment: Dietary supplement: Myo-Inositol 600 mg + Selenium 83 mcg

Detailed Description

Cytological classification of thyroid nodules (TIR 1-5) provides a useful tool in clinical practice. Each TIR class is statistically associated with a certain risk for malignancy, defining the recommended clinical action to undertake. The undetermined diagnosis (TIR 3) should represent less than 20% of patients, with an approximate risk of malignancy of 5-30%. Because of the variable risk of malignancy in the entire TIR 3 category, this is further divided into two groups: TIR 3A (low-risk follicular lesion): a heterogeneous group, with a low expected risk of malignancy (below 10%) and TIR 3B (follicular proliferation or suspected follicular neoplasia) with a higher expected risk of malignancy (15-30%). TIR3A nodules required close clinical and ultrasound follow-up and repetition of fine needle aspiration biopsy is recommended.

Selenium (Se) has the highest concentration in thyroid gland and selenium proteins are involved in thyroid hormone synthesis. Myo-inositol (MI) acts as second messengers both in thyroid differentiation and hormone synthesis and in inhibiting thyroid cells growth by inhibiting PI3K/AKT/mTOR pathway. Inositol is able to reduce NF-KB, a mediator of PI3K/AKT pathway, involved in cellular proliferation. In addition, in vitro studies demonstrated that inositol can reduce apoptosis and angiogenesis, but also inhibit the process of tumor metastasis and invasion by acting on the cytoskeleton. For this reason, this association could have a role in blocking thyroid nodule growth. Evidence from the literature highlights an important role of MI and Se in thyroid physiology and the maintenance of a euthyroid status. Particularly these micronutrients seem fundamental to counteract the onset and the worsening of thyroid alteration that could evolve into different pathological conditions if untreated. In this scenario, MI supplementation seemed to be involved also in the management of thyroidal benign nodules, with a possible effect on the size reduction. Interestingly, the administration of MI plus Se for 6 months of treatment period, was able to induce a morphological change by reducing the size and the stiffness of the nodules classified as class I or II (according to AACE/ACE/AME guidelines) in patients affected by subclinical hypothyroid.

Previous studies demonstrated a beneficial effect on subclinical hypothyroidism, restoring a euthyroid state and reducing both thyroid antibodies and TSH levels, mainly in patients affected by Hashimoto's thyroiditis. Based on these studies, nowadays, in clinical practice, oral supplementation with myoinositol and selenium is widespread and indicated in patients affected by subclinical hypotiroidism with values of TSH in the range 5-10 mcu/I with or without positivity to antibodies TPO-Ab/TG-Ab or in patients affected by Hashimoto's thyroiditis with TSH at the upper limit of the reference range.

The proposed study aims to evaluate the effect of selenium and myoinositol on possible risk factors for malignancy, as proliferation index, elastosonography characteristics (elasticity score) and TSH levels comparing a group of patients with selenium and myoinositol supplementation with a group without supplementation.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marialuisa Appetecchia, MD; Phone Number: 0039 0652666026; Email: marialuisa.appetecchia@ifo.it
• Study Contact Backup: Name: Giulia Puliani, MD, PhD; Phone Number: 0039 065266034; Email: giulia.puliani@ifo.it

Study Locations

• Italy
  • Rome, Italy, 00144
    • Recruiting
    • Regina Elena National Cancer Institute
    • Contact: Marialuisa Appetecchia, MD; Phone Number: 0039 0652666026; Email: marialuisa.appetecchia@ifo.it
    • Contact: Marta Bianchini, MD
    • Contact: Marilda Mormando, MD, PhD
    • Contact: Rosa Lauretta, MD
    • Contact: Giulia Puliani, MD, PhD
    • Contact: Ferdinando Marandino, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (>18 years old),
• both sexes,
• patients presenting thyroid nodules classified as TIR 3A, based on cytological evaluation on sample from the first fine needle aspiration (FNA),
• written Informed consent,
• Patients with appropriate material for subsequent immunocytochemical analysis of Ki-67 and PCNA

Exclusion Criteria:

• Patients with diagnosed thyroid malignancies of cytological diagnosis other than TIR3A
• pathological levels of the thyroid stimulating hormone (TSH) which required L-Thyroxine treatment starting
• pregnancy and/or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; No intervention
Experimental: Myo-inositol and selenium supplementation; Supplement with Myo-Inositol 600 mg + Selenium 83 mcg once a day for 6 months	Dietary supplement: Myo-Inositol 600 mg + Selenium 83 mcg; Myo-Inositol 600 mg + Selenium 83 mcg: 1 tablet once a day for 6 months; Other Names: Tiroxil 4.0

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of differences in elastosonography after six months in patients treated with selenium and myo-inositol and patients not treated (controls)	Changes in elastosonographic score after treatment (comparing treated and untreated patients)- Score varies from 1 (soft) to 4 (hard)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the inibition of the growth of thyroid nodules with Myo-inositol and Selenium supplementation	Changes in immunocytochemistry proliferation index (such as Ki-67 labeling index, from 0% to 100%) (comparing treated and untreated patients)	6 months
Evaluation of the differences in thyroid nodules volume in patients treated with selenium and myo-inositol	Changes in thyroid nodules volume (ml) in patients treated with selenium and myo-inositol (comparing treated and untreated patients)	6 months
Evaluation of the differences in thyroid hormones in patients treated with selenium and myo-inositol	Changes in thyroid hormones levels (TSH, FT3, FT4) in patients treated with selenium and myo-inositol (comparing treated and untreated patients)	6 months
Evaluation of the differences in anti-thyroid antibodies, in patients treated with selenium and myo-inositol	Changes in anti-thyroid antibodies (AbTg, AbTPO) in patients treated with selenium and myo-inositol (comparing treated and untreated patients)	6 months
Evaluation of the differences in thyroglobulin in patients treated with selenium and myo-inositol	Changes in thyroglobulin serum levels in patients treated with selenium and myo-inositol (comparing treated and untreated patients)	6 months
Correlation of cytological findings to histological parameters (subgroup of patients who will undergo surgical intervention)	Correlation of cytological findings to histological parameters	6 months

Collaborators and Investigators

• Sponsor: Regina Elena Cancer Institute
• Investigators: Principal Investigator: Marialuisa Appetecchia, MD, Regina Elena National Cancer Institute - IRCCS IFO

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2024
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: myo-inositol; selenium; TIR3A; indeterminate thyroid nodules
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Thyroid Neoplasms; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Nodule; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Trace Elements; Micronutrients; Antioxidants; Protective Agents; Vitamin B Complex; Vitamins; Selenium; Inositol
• Other Study ID Numbers: RS39/IRE/23(2869)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the end of the study, anonymized patient data will be shared on garrbox.it repository
• IPD Sharing Time Frame: After study result publication
• IPD Sharing Access Criteria: GARRbox user and working group
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No