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Understanding THRB and Thyroid Hormone Resistance

The thyroid gland produces hormones that regulate metabolism, energy, temperature, and many aspects of overall health. THRB is the gene that encodes the thyroid hormone receptor beta. This receptor helps cells respond to the active thyroid hormone, T3. Variations in THRB can change how well cells detect and respond to thyroid hormone. In some cases this causes thyroid hormone resistance, a condition in which blood hormone levels may be normal or elevated while symptoms of low thyroid activity persist.

How THRB Variants Can Affect Health

When THRB function is reduced, tissues that rely on the receptor may receive a weaker signal from circulating T3. That can lead to symptoms similar to hypothyroidism, such as fatigue, cold intolerance, weight gain, slowed metabolism, brain fog, and low exercise tolerance. Lab tests that measure TSH alone can miss resistance because TSH, free T4, and free T3 levels may not reflect how tissues are responding. Interpreting labs together with symptoms is important.

Recommended Tests and Monitoring

  • Comprehensive thyroid panel: TSH, free T4, free T3.
  • Consider reverse T3 if symptoms are present despite normal TSH and free hormones.
  • Repeat testing when symptoms change or after treatment adjustments.
  • Work with your healthcare provider to interpret results in the context of symptoms and medical history.

Dietary and Nutrient Support

Nutrition does not change your DNA, but it can support healthy thyroid hormone production and conversion. A balanced anti-inflammatory Mediterranean style diet is a good foundation. Focus on whole foods, colorful vegetables, fatty fish, nuts, seeds, legumes, olive oil, and moderate lean protein.

  • Selenium: important for the enzymes that convert T4 to active T3. Good sources include Brazil nuts, seafood, and organ meats.
  • Zinc: supports thyroid hormone synthesis and receptor function. Found in oysters, red meat, poultry, beans, and nuts.
  • Vitamin A: needed for thyroid hormone action in tissues. Found in liver, eggs, dairy, and orange or dark green vegetables.
  • Vitamin D: plays a role in immune regulation and may support thyroid health. Obtain from safe sun exposure, fatty fish, fortified foods, or supplementation if deficient.
  • Iodine: required for thyroid hormone synthesis. Most people obtain adequate iodine from iodized salt, seafood, dairy, and eggs. Avoid excessive intake and aim for moderate levels.

Supplements to Consider

Supplement use should be personalized with input from your healthcare provider and based on dietary intake and lab testing.

  • Selenium 100 to 200 mcg daily may be helpful if dietary intake is low.
  • Zinc 10 to 30 mg daily when deficiency is suspected or confirmed.
  • Vitamin D3 if levels are low; dosing should be guided by a blood test.
  • Multinutrient supplements or targeted thyroid support formulations if recommended by your provider.

Lifestyle Strategies

  • Prioritize quality sleep and aim for consistent sleep schedules.
  • Manage stress through practices such as mindfulness, breathing exercises, gentle movement, and therapy when needed.
  • Reduce exposure to endocrine disruptors by avoiding plastics containing BPA, choosing glass or stainless steel for food storage, and minimizing use of personal care products with suspicious chemicals.
  • Maintain regular physical activity tailored to your energy levels. Gentle resistance training and walking are good starting points.

When to See a Specialist

If you have persistent hypothyroid symptoms despite normal standard thyroid tests, or if your THRB genotype suggests increased risk for resistance, consult a thyroid specialist or endocrinologist. Specialist evaluation can include more detailed hormone testing, assessment for central or peripheral resistance, genetic counseling if appropriate, and personalized treatment strategies.

Two effect alleles (TT genotype for rs28933408)

The TT genotype is an extremely rare variant associated with thyroid hormone resistance. This means your cells may have decreased sensitivity to T3 even when blood hormone levels appear normal or high. Common symptoms include fatigue, low metabolic rate, weight gain, brain fog, and exercise intolerance. Standard TSH testing may not reflect tissue-level resistance, so comprehensive testing with free T3, free T4, and TSH is essential. Interpret results together with symptoms.

Supporting strategies:

  • Comprehensive thyroid panel including free T3, free T4, and TSH.
  • Consider testing reverse T3 if clinically indicated.
  • Dietary support rich in selenium, zinc, vitamins A and D, and moderate iodine intake.
  • Follow an anti-inflammatory Mediterranean style diet and reduce exposure to endocrine disruptors such as BPA.
  • Prioritize sleep, stress management, and appropriate physical activity.
  • Work closely with a thyroid specialist for personalized evaluation and treatment options.
One effect allele (GT genotype for rs28933408)

Carrying one effect allele is associated with a risk for thyroid hormone resistance, a rare condition where tissues respond less effectively to thyroid hormone. You may experience symptoms like fatigue, weight gain, and slow metabolism even if blood hormones look normal. Misdiagnosis as central hypothyroidism is possible without careful interpretation.

Recommended actions:

  • Obtain a full thyroid panel: TSH, free T3, free T4, and consider reverse T3 when appropriate.
  • Support thyroid health with dietary sources of selenium, zinc, vitamins A and D, and moderate iodine.
  • Adopt an anti-inflammatory Mediterranean style diet and limit exposure to endocrine disruptors.
  • Focus on sleep hygiene and stress reduction techniques.
  • Consult a thyroid specialist if symptoms persist despite normal lab values.
Zero effect alleles (GG genotype for rs28933408)

The GG genotype is the typical genotype and indicates normal THRB receptor function. Your tissues are likely to respond appropriately to T3, supporting normal metabolic regulation and energy balance. You are not predisposed to thyroid hormone resistance from this variant.

Maintenance recommendations:

  • Maintain a balanced Mediterranean style diet with adequate selenium, zinc, vitamins A and D, and moderate iodine from foods like seafood, nuts, eggs, and colorful vegetables.
  • Avoid endocrine disruptors when possible and support good sleep and stress management routines.
  • Continue routine health monitoring and discuss any new symptoms with your healthcare provider.

Important Notice

PlexusDx provides educational information about genetic predispositions and does not provide medical advice. This information is not a diagnosis or a substitute for professional medical care. Always consult your healthcare provider or a qualified specialist before making changes to your diet, supplement routine, or medical treatment based on genetic results. Personalized care from a clinician is essential for safe and effective management.