Main thyroid hormone produced by thyroid gland
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Thyroid Function
weight gain
Free T4 (thyroxine) is the unbound, biologically active form of the main thyroid hormone circulating in your blood. Your thyroid gland produces mostly T4 (about 80-90% of thyroid hormone output), which then gets converted to the more potent T3 in your tissues. Only about 0.03% of total T4 is "free"(unbound to proteins like thyroid-binding globulin)—the rest is bound and inactive.
Here's the key insight:T4 is essentially a "prohormone"—it's not the final active form. Think of T4 as the raw material that your body converts into the 3-4x more potent T3 hormone where it's needed (liver, kidneys, muscles, brain). About 80% of circulating T3 comes from peripheral conversion of T4 to T3, not from direct thyroid secretion. This conversion process depends on enzymes called deiodinases, which require selenium, zinc, and iron to function properly.
This is why some people have normal TSH and normal Free T4 but still have hypothyroid symptoms—if they're not efficiently converting T4 to T3 (due to stress, nutrient deficiencies, medications, or chronic illness), they won't have enough of the active hormone. That's why checking Free T3 in addition to TSH and Free T4 is essential for a complete thyroid assessment.
| Range Type | Level | Significance |
|---|---|---|
| Optimal (Longevity) | 1.0-1.5 ng/dL | Mid-upper normal range;best metabolic function and symptom control. Many functional medicine doctors target this range. |
| Low-Normal | 0.8-1.0 ng/dL | Within standard range but may have subtle hypothyroid symptoms. Consider increasing levothyroxine dose if symptomatic. |
| Low (Hypothyroid) | <0.8 ng/dL | Hypothyroidism;insufficient thyroid hormone production. Requires treatment with levothyroxine. Check TSH to confirm. |
| High (Hyperthyroid) | >1.8 ng/dL | Hyperthyroidism;excess thyroid hormone. Causes rapid heart rate, anxiety, weight loss. Check TSH (will be low). Evaluate for Graves'disease. |
Levothyroxine (Synthroid, Levoxyl, Tirosint, generic):Synthetic T4 hormone. Standard starting dose 25-50 mcg (lower if elderly or heart disease), titrate every 6-8 weeks based on TSH/Free T4 until optimal. Most patients need 75-150 mcg daily.
Timing:Take on empty stomach, 30-60 minutes before breakfast. Absorption impaired by calcium, iron, coffee, antacids—separate by 4 hours.
Goal:Free T4 in upper half of normal range (1.0-1.5 ng/dL), TSH 0.5-2.5 mIU/L, and resolution of symptoms.
Since 80% of T3 comes from T4 conversion, you need adequate Free T4 PLUS efficient conversion:
Selenium (200 mcg/day):Essential for deiodinase enzymes that convert T4→T3. Brazil nuts (2-3/day), seafood, organ meats, or supplement.
Zinc (15-30 mg/day):Required for thyroid hormone receptor function and T4→T3 conversion. Oysters, red meat, pumpkin seeds.
Iron (ferritin >70 ng/mL):Iron deficiency impairs both thyroid hormone production and conversion. Check ferritin;supplement if low.
Manage stress:Chronic stress/elevated cortisol shifts T4 conversion toward inactive reverse T3 instead of active T3. Prioritize sleep, meditation, stress reduction.
If Free T4 is optimal but Free T3 remains low despite addressing nutrients/stress, consider adding T3:
Liothyronine (Cytomel):Synthetic T3. Add 5-10 mcg to existing levothyroxine, split into 2 doses. Reassess in 6-8 weeks.
Combination T4/T3 therapy:Some compounding pharmacies offer custom ratios (e.g., 4:1 or 5:1 T4:T3).
Natural desiccated thyroid (NDT):Armour Thyroid, NP Thyroid contain both T4 and T3. Some patients prefer it but evidence is mixed.
Hashimoto's causes progressive thyroid damage, leading to low Free T4 over time.
Selenium:Reduces TPO antibodies by ~40% in studies. 200 mcg/day.
Gluten-free diet:May reduce antibodies in subset of patients due to molecular mimicry.
Vitamin D optimization:Deficiency linked to higher autoimmune thyroid disease risk. Target >40 ng/mL.
High Free T4 with low TSH indicates hyperthyroidism (Graves'disease, toxic nodule, thyroiditis).
Treatment:Antithyroid drugs (methimazole, PTU), radioactive iodine, or surgery. Work with endocrinologist.
Only ~0.03% of T4 is "free"(unbound). The rest is bound to thyroid-binding globulin (TBG), albumin, and transthyretin. Bound T4 is inactive. Free T4 reflects biologically active hormone and is preferred over Total T4, which fluctuates with binding protein levels (pregnancy, estrogen, liver disease).
Source:Thienpont LM, et al. Standardization of free thyroxine measurements:critical considerations. Eur Thyroid J. 2015;4(Suppl 1):51-58.
T4 has relatively low intrinsic activity. It's converted to T3 by deiodinases in peripheral tissues (liver, kidney, muscle, brain). About 80% of circulating T3 comes from T4→T3 conversion, not direct thyroid secretion. T3 is 3-4x more potent than T4 at binding thyroid receptors. This is why some patients with normal Free T4 still have symptoms if conversion is impaired.
Source:Bianco AC, Kim BW. Deiodinases:implications of the local control of thyroid hormone action. J Clin Invest. 2006;116(10):2571-2579.
Standard treatment goal is to normalize TSH (0.5-2.5 mIU/L) and bring Free T4 into mid-upper normal range (1.0-1.5 ng/dL). However, 10-20% of patients on levothyroxine report persistent symptoms despite normal TSH/Free T4, often due to low Free T3. Adding T3 (liothyronine) may benefit this subset.
Source:Jonklaas J, et al. Guidelines for the treatment of hypothyroidism. Thyroid. 2014;24(12):1670-1751.
Deiodinase enzymes that convert T4→T3 are selenoproteins requiring selenium. Selenium deficiency impairs T3 production and increases reverse T3. Selenium supplementation (200 mcg/day) improves thyroid hormone metabolism and reduces TPO antibodies in Hashimoto's patients by ~40%.
Source:Ventura M, et al. Selenium and thyroid disease:from pathophysiology to treatment. Int J Endocrinol. 2017;2017:1297658.
Low Free T4 with low or inappropriately normal TSH indicates pituitary or hypothalamic dysfunction, not primary thyroid failure. Prevalence is ~1:20,000-80,000. Often associated with other pituitary hormone deficiencies (GH, ACTH, LH/FSH). Requires pituitary MRI and endocrine workup.
Source:Persani L, et al. Central hypothyroidism. J Clin Endocrinol Metab. 2018;103(11):4126-4136.
| Provider | Includes | Annual Cost | Biomarkers |
|---|---|---|---|
 Superpower | ✓ | $199 | 100+ (150 with ratios) |
 WHOOP Advanced Labs | — | $349 | 65 |
 Labcorp OnDemand | ✓ | $398 | 30+ |
| ✓ | $486 | 40+ | |
| ✓ | $468 | 83 | |
| ✓ | $349 | 100+ | |
 InsideTracker | — | $680 | 54 |
 Function Health | ✓ | $365 | 100+ |
| — | $250 | 65 | |
| ✓ | $495 | 70+ | |
| ✓ | $895 | 100+ | |
| ✓ | $1950 | 150+ | |
| — | $399 | 100+ | |
| — | $Varies | 75+ | |
| ✓ | $190 | 100+ | |
| — | $99 | 50 | |
| ✓ | $125 | 60 | |
| — | $199 | 50 | |
| ✓ | $499 | 120+ | |
| ✓ | $4188 | 80+ | |
| ✓ | $375 | 85 | |
| ✓ | $700 | 129 |
16 providers include this biomarker in their panels
This information is for educational purposes only and is not medical advice. Always consult with a qualified healthcare provider about your specific health needs.
