Thyroid | DIO2 (rs225014)

Understanding DIO2 and How It Impacts Thyroid Activation

The thyroid gland makes hormones that control metabolism, energy, and reproductive health. The main hormone released by the thyroid is thyroxine, or T4. In tissues such as the brain, muscles, heart, and reproductive organs, an enzyme called type 2 deiodinase, produced by the DIO2 gene, converts T4 into the active hormone triiodothyronine, or T3. T3 is the form that binds to cellular receptors and turns on metabolic processes.

Variants in the DIO2 gene can change how well this conversion happens. When conversion is slower or reduced, tissues can have less active T3 even when blood tests like TSH or total T4 look normal. This can lead to symptoms such as persistent fatigue, difficulty managing weight, brain fog, cold sensitivity, and changes in menstrual cycles or fertility. Knowing your DIO2 genotype can help guide nutrition, monitoring, and conversations with your healthcare provider.

What This Means for You

• Normal blood tests do not always reflect tissue-level activation of thyroid hormone.
• DIO2 variation can contribute to symptoms typical of low thyroid function even with standard laboratory values in the reference range.
• Diet, nutrients, lifestyle habits, and medication choices can influence T4 to T3 conversion and how you feel.

Genetic Interpretations

Diet and Nutrients to Support T4 to T3 Conversion

Certain nutrients are essential for the enzymes and processes that make and activate thyroid hormones. Focus on whole foods that supply these nutrients rather than high dose supplements unless directed by your provider.

• Selenium: Required for deiodinase activity. Sources include Brazil nuts (1 to 2 nuts per day provide substantial selenium), seafood, sardines, tuna, and sunflower seeds.
• Iodine: Needed for thyroid hormone synthesis. Sources include iodized salt, seaweed (use cautiously if you have thyroid disease), seafood, and dairy. Avoid very high intakes unless advised by your clinician.
• Iron: Low iron can impair thyroid hormone production. Include lean meats, poultry, fish, legumes, and iron-rich leafy greens. Monitor ferritin with blood testing if you have symptoms.
• Zinc: Supports thyroid hormone metabolism. Found in oysters, beef, pumpkin seeds, and chickpeas.
• Vitamin A: Important for thyroid hormone action and receptor sensitivity. Sources include sweet potatoes, carrots, liver, and orange or dark green vegetables.
• Kaempferol: A flavonoid that may support deiodinase function and reduce oxidative stress. Present in apples, onions, grapes, kale, and broccoli.

Supplement Considerations

Supplements can help when dietary intake is insufficient, but talk with your healthcare provider before starting any new supplement, especially if you are taking thyroid medication or have thyroid disease.

• Multivitamin with iodine and zinc if dietary intake is limited.
• Selenium supplement typically in the range of 50 to 200 mcg per day may be considered when intake is low. Avoid excessive selenium.
• Iron supplementation only if ferritin is low and under medical guidance.
• Vitamin A from food is preferred. Supplements should be used cautiously because excess vitamin A can be harmful.
• A personalized approach is best for adding T3 hormone medication. Never self-prescribe thyroid hormones.

Lifestyle Habits That Help Thyroid Activation

• Stress management: Chronic stress raises cortisol which can interfere with T4 to T3 conversion. Practices such as sleep hygiene, mindfulness, moderate exercise, and relaxation techniques can improve outcomes.
• Regular physical activity: Exercise can enhance metabolic rate and support healthy hormone signaling. Aim for a mix of aerobic and resistance training.
• Avoid environmental toxins: Certain chemicals such as excess fluoride, perchlorate, and some endocrine disrupting compounds can impair thyroid function. Reduce exposure when possible.
• Healthy weight management: Gradual, sustainable weight changes that include balanced nutrition and activity help hormone balance.
• Consistent monitoring: Keep track of symptoms and routine labs and discuss patterns with your provider.

Recommended Blood Tests and Monitoring

• TSH: Screening test for thyroid function.
• Free T4 and free T3: Evaluate circulating inactive and active hormone levels.
• Reverse T3: Can help explain symptoms when free T3 is low and TSH is normal.
• Ferritin and iron studies, selenium status when clinically indicated, and other nutrient tests based on symptoms.
• Repeat testing and symptom review as advised by your clinician, especially if you change medication or start supplements.

Medication and Clinical Conversations

If you have ongoing symptoms despite normal labs, discuss the following with your healthcare provider:

• Whether more comprehensive testing could clarify tissue level activation.
• Options for combination T4 plus T3 therapy versus T4-only therapy if you are symptomatic on T4 alone.
• The risks and benefits of starting any hormone medication and how to monitor response and safety.

Final Notes and Disclaimer

PlexusDx provides educational information about genetic predispositions and health. This content is not medical advice. Always consult with your healthcare provider to interpret genetic results in the context of your medical history, symptoms, and laboratory testing. Your provider can recommend personalized testing, nutrition, supplements, lifestyle changes, and medication options based on your unique needs.