What is the role of vitamins and other hormones, such as Vitamin D, cortisol, growth hormone, and insulin-like growth factor-1 (IGF-1), in thyroid hormone synthesis in the general adult population, particularly those with concerns about thyroid function?

Role of Vitamins and Hormones in Thyroid Hormone Synthesis

Essential Micronutrients for Thyroid Function

Iodine, iron, and selenium are the three critical micronutrients directly required for thyroid hormone synthesis, while vitamin D appears to modulate the GH/IGF-I axis rather than directly participating in thyroid hormone production. 1

Iodine: The Primary Substrate

• Iodine is absolutely essential for thyroid hormone synthesis, with daily requirements of 150 μg/day in adults and 150-249 μg/day in pregnancy 2, 1
• TSH regulates all steps of thyroid hormone biosynthesis, including iodide uptake, oxidation and organification of iodide, and secretion of T4 and T3 into circulation 1
• When iodine is deficient, chronic TSH stimulation causes compensatory thyroid enlargement (goitre) to maximize iodine uptake and recycling 1
• TSH levels alone are not a sensitive indicator of iodine status, as concentrations are usually maintained within normal range despite frank iodine deficiency 1

Iron: Critical for Enzyme Function

• Iron is essential for thyroid peroxidase (TPO) activity, the heme-containing enzyme that catalyzes thyroid hormone synthesis 1
• Iron deficiency impairs thyroid hormone synthesis by reducing TPO activity and affects the tissue conversion of T4 to T3 1
• Iron deficiency anemia is associated with thyroid dysfunction, particularly subclinical hypothyroidism, and can blunt the efficacy of iodine supplementation 1
• The mechanism involves both direct effects on TPO enzyme function and indirect effects on pituitary TSH secretion 1

Selenium: Required for Hormone Conversion

• Selenium is required for the deiodination of T4 to T3 via the selenoenzyme Type 1 5'-deiodinase 1
• This conversion is critical because T3 is the more metabolically active thyroid hormone 3, 4

Vitamins and Indirect Hormonal Influences

Vitamin D: Indirect Effects Through IGF-I

• Vitamin D does not directly participate in thyroid hormone synthesis but modulates circulating IGF-I levels, which may have secondary effects on thyroid function 5, 6
• Treatment with 7000 IU vitamin D3/week significantly increased IGF-I levels by 31.3±36.7 ng/ml (P=0.01) in adults 5
• GH directly regulates renal 1 alpha-hydroxylase activity, and vitamin D increases circulating IGF-I, creating a complex interplay between vitamin D and the GH/IGF-I system 6
• Vitamin D levels are commonly lower in patients with GH deficiency than in controls, though data on the impact of GH treatment on vitamin D levels are conflicting 6

Vitamin A: Unclear Direct Role

• Historical data suggested vitamin A therapy in vitamin A-deficient patients produced increases in T3, T4, and free thyroid hormone indices, with a concomitant increase in retinol binding protein 7
• However, vitamin A therapy in normal individuals produced only a transient decrease in T3 and T4 after 1 week, with thyroid function returning to normal after 2 weeks 7
• The relationship appears to be related to retinol binding protein metabolism rather than direct effects on thyroid hormone synthesis 7

Other B Vitamins

• Vitamin B12 is mentioned as beneficial for thyroid function, particularly in Hashimoto's thyroiditis, though the mechanism is not well-defined in the available evidence 4
• Diets rich in vitamins B12, D3, and A are increasingly prescribed for patients with Hashimoto's thyroiditis, with benefits at immune, endocrine, and biomolecular levels 4

Clinical Implications

Screening and Diagnosis Considerations

• TSH is the primary screening test for thyroid dysfunction, with follow-up testing of serum T4 levels in persons with persistently abnormal TSH to differentiate subclinical from overt dysfunction 2, 1
• Multiple TSH tests over a 3-6 month interval are recommended to confirm abnormal findings, as TSH can vary by up to 50% day-to-day 2
• TSH secretion is highly sensitive to factors other than thyroid disorders, including acute illness, drugs (iodine, dopamine, glucocorticoids), adrenal insufficiency, and pregnancy 2

Nutritional Management

• For patients with thyroid concerns, ensure adequate intake of iodine (150 μg/day), iron, and selenium before attributing symptoms to primary thyroid disease 1, 3, 4
• The Mediterranean diet, rich in these critical elements, benefits patients at immune, endocrine, and biomolecular levels and may improve inflammation in thyroiditis 4
• Iron deficiency should be corrected before or concurrent with iodine supplementation, as iron deficiency can blunt the efficacy of iodine therapy 1

Common Pitfalls

• Do not rely on a single TSH value to establish thyroid dysfunction diagnosis, as serial measurements are essential 2
• Do not assume vitamin D or other hormones like cortisol or IGF-I directly participate in thyroid hormone synthesis—their effects are indirect and modulatory 5, 6
• Avoid over-supplementation with iodine, as excessive intake (>300 μg/L urinary iodine) poses risk of adverse health consequences including iodine-induced hyperthyroidism and autoimmune thyroid disease 2