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.