Subclinical hypothyroidism represents one of the most frequent grey areas in thyroid health. It is usually defined by increased thyroid-stimulating hormone (TSH) levels, while free thyroxine (fT4) and free triiodothyronine (fT3) remain within the reference range.
For healthcare professionals, this condition raises an important clinical question: how should this early stage be managed?
In many cases, subclinical hypothyroidism is asymptomatic and detected through laboratory tests, when routine blood work reveals an isolated TSH elevation. Although the picture may remain stable over time, in some patients it can progress toward overt hypothyroidism. One of the most common underlying causes is Hashimoto’s thyroiditis (autoimmune thyroiditis), in which the immune system targets the thyroid gland, leading to positive thyroid antibodies and, frequently, non-specific symptoms such as fatigue, mood changes or menstrual irregularity.
In this context, growing attention has been directed toward nutritional strategies able to support thyroid physiology before pharmacological treatment becomes necessary. Among these, the combination of myo-inositol and selenium has gained increasing scientific interest for its potential role in TSH signalling, thyroid hormone synthesis and the modulation of thyroid autoimmunity.
Why subclinical hypothyroidism deserves clinical attention
When TSH rises but thyroid hormones remain normal
Subclinical hypothyroidism is often described as a mild or early thyroid dysfunction. However, its clinical relevance should not be underestimated. The presence of elevated TSH may reflect an increased stimulation of the thyroid gland, even when circulating thyroid hormones are still within normal limits.
This biochemical profile is particularly common in patients with autoimmune thyroiditis, where progressive inflammatory damage to the thyroid tissue may gradually affect thyroid function. In some patients the condition remains stable; in others, it may evolve toward overt hypothyroidism.
The uncertainty surrounding this progression explains why subclinical hypothyroidism is frequently managed with careful monitoring, especially when TSH levels are below the threshold at which levothyroxine is clearly indicated (NICE, 2025).
Thyroid autoimmunity and the burden beyond laboratory values
Hashimoto’s thyroiditis is one of the main causes of thyroid dysfunction in clinical practice. In this condition, thyroid autoimmunity is usually reflected by the presence of thyroid antibodies, particularly thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb).
TPO is the enzyme that drives iodine organification during hormone synthesis, while thyroglobulin (TG) is the protein from which thyroid hormones are produced. Antibodies against these two targets are markers of immune activity against the gland and are commonly used to confirm an autoimmune origin of the dysfunction.
Although subclinical hypothyroidism may be asymptomatic, some patients may report non-specific symptoms that can affect quality of life, such as fatigue, weakness, mood changes and menstrual cycle alterations. Moreover, if left untreated or inadequately monitored, it may progress to overt hypothyroidism, especially in the presence of thyroid autoimmunity. For this reason, early identification may help clinicians define appropriate monitoring strategies and timely supportive interventions.
Myo-inositol and selenium: a physiological rationale for thyroid function
Myo-inositol and TSH signaling
Myo-inositol acts as a TSH second messenger: within thyroid follicular cells, it is part of the phosphatidylinositol signalling pathway activated when TSH binds to its receptor.
Through this pathway, myo-inositol plays a key role in thyroid physiology by regulating iodine organification and thyroid hormone biosynthesis through the generation of hydrogen peroxide in thyrocytes. Its depletion may impair thyroid function and contribute to the development of hypothyroidism, as the thyroid cell becomes less responsive to TSH stimulation (Paparo et al., 2022).
Myo-inositol may therefore support the physiological response of the thyrocyte to TSH and contribute to the maintenance of normal thyroid function (Nordio and Pajalich, 2013).
Selenium, oxidative balance and thyroid autoimmunity
Selenium is an essential trace element for thyroid health. The thyroid gland contains high concentrations of selenium-dependent enzymes, including glutathione peroxidases and deiodinases, which are involved in antioxidant protection and thyroid hormone metabolism.
In autoimmune thyroiditis, oxidative stress and inflammation contribute to the progression of tissue damage. Selenium may help support antioxidant defence mechanisms and has been investigated for its ability to influence thyroid antibody levels (Payer et al., 2022).
For this reason, the association of myo-inositol and selenium has a complementary rationale: myo-inositol supports TSH signalling, while selenium contributes to normal thyroid function and antioxidant protection (Nordio and Pajalich, 2013).
Clinical evidence on myo-inositol and selenium in subclinical hypothyroidism
Several studies support combining myo-inositol and selenium in subclinical hypothyroidism with thyroid autoimmunity. The effect is consistent: TSH closer to physiological values, lower antibody titres and better wellbeing, with greater benefit than selenium alone.
In particular, Nordio and Pajalich first showed that adding myo-inositol to selenium brought TSH closer to normal, outperforming selenium alone (Nordio and Pajalich, 2013); due to its action as a TSH second messenger, myo-inositol helps reduce TSH toward physiological concentrations.
Nordio and Basciani confirmed reductions in TSH, TPOAb and TgAb, restoring euthyroidism in Hashimoto’s thyroiditis, with or without subclinical hypothyroidism, earlier than selenium alone (Nordio and Basciani, 2017), and Pace et al. found TSH fell faster and further with selenium plus myo-inositol (Pace et al., 2020).
The benefit holds across populations: in women of reproductive age, six months of 600 mg myo-inositol and 83 mcg selenium improved TSH, autoimmunity markers and ultrasound, and eased symptoms such as fatigue, weight changes and cold intolerance (Payer et al., 2022), with possible prevention of subclinical hypothyroidism in pregnancy (Porcaro and Angelozzi, 2018); in adults with migraine and Hashimoto’s thyroiditis, it lowered TSH and improved migraine outcomes (Di Lorenzo et al., 2026).
What this evidence means for healthcare professionals
Supporting thyroid physiology in the subclinical stage
Taken together, the available studies describe a consistent direction of effect in patients with subclinical hypothyroidism and thyroid autoimmunity. In summary, the evidence points to:
- Patient profiles: adults with autoimmune (Hashimoto’s) thyroiditis and subclinical hypothyroidism, including women of reproductive age and during pregnancy, and selected comorbid populations such as patients with migraine.
- Biochemical outcomes: TSH brought closer to physiological values and, in several studies, reduced TPOAb and TgAb titres, together with improved thyroid hormone parameters and ultrasound findings.
- Clinical and symptom outcomes: improvement in non-specific symptoms (fatigue, mood changes, menstrual irregularity) and in perceived wellbeing, with earlier benefit when myo-inositol is combined with selenium.
This does not replace clinical evaluation or pharmacological treatment when indicated. Standard pharmacological therapy remains the reference option in overt hypothyroidism and in selected cases of subclinical hypothyroidism, according to clinical guidelines and patient-specific risk factors.
In some cases, however, myo-inositol and selenium may represent a supportive nutritional strategy to be considered within a broader monitoring plan.
Subclinical hypothyroidism and thyroid health: a balanced approach
Subclinical hypothyroidism sits between simple observation and pharmacological intervention. This is why it requires a measured, evidence-based approach. For clinicians, the priority remains to evaluate:
- TSH levels
- thyroid hormone values
- thyroid antibodies
- ultrasound findings
- symptoms
- reproductive stage
- comorbidities
- individual risk factors.
Within this context, the evidence on myo-inositol and selenium provides a physiological and clinically investigated option for supporting thyroid function in selected patients with autoimmune thyroiditis.
The growing body of research suggests that acting early on thyroid health may help support euthyroidism, reduce autoimmune markers and improve patient wellbeing, while maintaining the central role of medical monitoring and clinical decision-making.
Bibliography:
Di Lorenzo C, Nordio M, Brongo F, et al. Myo-inositol and selenium (MYSE) supplementation is associated with favorable changes in thyroid parameters and migraine outcomes in patients with migraine and Hashimoto’s thyroiditis: a retrospective cohort study. Nutrients. 2026;18(10):1554. https://doi.org/10.3390/nu18101554
NICE. Thyroid disease: assessment and management. NICE guideline NG145. Updated 2025. https://www.nice.org.uk/guidance/ng145
Nordio M, Basciani S. Myo-inositol plus selenium supplementation restores euthyroid state in Hashimoto’s patients with subclinical hypothyroidism. Eur Rev Med Pharmacol Sci. 2017;21(2 Suppl):51-59. https://pubmed.ncbi.nlm.nih.gov/28724185
Nordio M, Pajalich R. Combined treatment with myo-inositol and selenium ensures euthyroidism in subclinical hypothyroidism patients with autoimmune thyroiditis. J Thyroid Res. 2013;2013:424163. https://doi.org/10.1155/2013/424163
Pace C, Tumino D, Russo M, et al. Role of selenium and myo-inositol supplementation on autoimmune thyroiditis progression. Endocr J. 2020;67(11):1093-1098. https://doi.org/10.1507/endocrj.EJ20-0062
Paparo SR, Ferrari SM, Patrizio A, et al. Myo-inositol in autoimmune thyroiditis. Front Endocrinol (Lausanne). 2022;13:930756. https://doi.org/10.3389/fendo.2022.930756
Payer J, Jackuliak P, Kuzma M, Dzupon M, Vanuga P. Supplementation with myo-inositol and selenium improves the clinical conditions and biochemical features of women with or at risk for subclinical hypothyroidism. Front Endocrinol (Lausanne). 2022;13:1067029. https://doi.org/10.3389/fendo.2022.1067029
Porcaro G, Angelozzi P. Myo-inositol and selenium prevent subclinical hypothyroidism during pregnancy: an observational study. Int J Med Device Adjuv Treat (IJMDAT). 2018;1:e137.
