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Understanding SERPINA7 and Thyroxine-Binding Globulin (TBG)

The thyroid gland makes hormones that regulate metabolism, energy, temperature, and reproductive health. Most thyroid hormones in the bloodstream are bound to carrier proteins. Thyroxine-binding globulin, or TBG, is the main carrier and is produced from the SERPINA7 gene. Genetic variations in SERPINA7 can change how much TBG your body makes. Lower TBG levels can make total thyroid hormone lab results appear low even when the active, free hormones are normal. Knowing your SERPINA7 genotype helps avoid misinterpretation of lab tests and unnecessary treatment changes.

Why this matters for lab testing and care

  • Total T4 and total T3 measure both bound and free hormone. Low TBG lowers total hormone values even when free hormone is adequate.
  • Free T4, free T3, and TSH are the most informative tests when TBG variation is suspected.
  • Awareness of TBG deficiency prevents misdiagnosis of hypothyroidism and inappropriate thyroid medication dosing.

Genetic Interpretation

2 effect alleles — TT (TBG deficiency)

Carrying two effect alleles (TT) is associated with markedly reduced or absent TBG production. Expect significantly low total T4 and total T3 on standard labs. Despite low total values, free T4, free T3, and TSH are usually normal, and most people are clinically euthyroid without symptoms. When the TT genotype is present, always request free T4, free T3, and TSH to accurately assess thyroid function and to avoid inappropriate thyroid hormone treatment based only on total hormone levels.

1 effect allele — AT (TBG carrier)

With one effect allele (AT), TBG levels are typically about half of normal. This partial reduction can cause lower total T4 and total T3 results, while free T4, free T3, and TSH usually remain within normal ranges. Carriers can be mistaken for having low thyroid function if only total hormone levels are reviewed. To ensure accurate evaluation, request free T4, free T3, and TSH whenever thyroid testing is performed.

0 effect alleles — AA (typical TBG levels)

Having two non-effect alleles (AA) is associated with normal TBG production. Total thyroid hormone measurements generally reflect true thyroid status. Standard thyroid care and testing remain appropriate, but general thyroid-supportive nutrition and lifestyle measures can help maintain optimal thyroid health.

Supporting Thyroid Health: Diet, Supplements, and Lifestyle

Genetic variation in SERPINA7 affects how thyroid hormones are carried in the blood, not the hormone production itself in most cases. General nutritional and lifestyle choices can support healthy thyroid function and overall well-being.

Nutrition essentials

  • Iodine — crucial for thyroid hormone synthesis. Include iodized salt in cooking and eat iodine-rich foods such as seaweed, fish, and dairy if tolerated. Avoid excessive iodine intake.
  • Selenium — helps convert T4 into the active T3 and supports antioxidant defenses in the thyroid. Sources include Brazil nuts (one to two per day), seafood, eggs, and whole grains.
  • Zinc — supports thyroid hormone metabolism and immune function. Found in red meat, poultry, shellfish, pumpkin seeds, and legumes.
  • Vitamin D — plays roles in immune regulation and may influence thyroid autoimmunity. Get safe sun exposure, eat fatty fish, and consider testing levels if deficiency is suspected.
  • Vitamin A — supports thyroid hormone signaling and cell health. Obtain from liver in moderation, fatty fish, eggs, and carotenoid-rich vegetables like carrots and sweet potatoes.

Practical supplement considerations

  • Before starting supplements, check blood levels when possible and discuss with a healthcare provider.
  • Selenium: a common supplemental dose is 50 to 200 mcg daily, but avoid chronic high doses that can cause toxicity.
  • Vitamin D: supplement dosing depends on baseline levels. A common maintenance dose is 1,000 to 2,000 IU daily, adjusted to achieve optimal blood levels.
  • Iodine: most people get adequate iodine from iodized salt and food. Avoid high-dose iodine supplements unless recommended by a provider.
  • Zinc: typical supplemental doses range from 8 to 15 mg daily; higher doses should be taken only under supervision.

Lifestyle habits that support thyroid wellness

  • Limit exposure to endocrine disruptors: reduce use of plastics for food storage, avoid heating food in plastic containers, and choose BPA-free products when possible.
  • Maintain consistent nutrition: avoid extreme calorie restriction and erratic diets that can affect hormone balance.
  • Manage stress: chronic stress influences thyroid metabolism and overall hormonal balance. Regular sleep, relaxation practices, and moderate exercise help modulate stress.
  • Regular physical activity: supports metabolism, body composition, and mood. Aim for a mix of aerobic and strength training most weeks.
  • Routine monitoring: especially when starting or changing medications or supplements that affect thyroid function.

Recommended Testing and When to Share Your Genotype

  • Request free T4, free T3, and TSH for accurate thyroid assessment, especially if total T4 or total T3 results are low while clinical symptoms are absent.
  • If genetic testing shows an SERPINA7 variant associated with reduced TBG, inform your clinician so interpretation of thyroid labs accounts for altered binding protein levels.
  • Consider periodic thyroid testing if symptoms develop, or if medications, pregnancy, or other health changes occur that can influence thyroid status.

Important Notice

PlexusDx provides genetic education and information about predispositions only. This content does not provide medical advice, diagnosis, or treatment. Always consult with your healthcare provider to interpret test results, decide on testing strategies, and make changes to medications, supplements, or medical care.