Hormones

Thyroid (Levothyroxine / Liothyronine T3/T4)

Evidence: strong_human

Mechanism of Action

Levothyroxine (T4) is a prohormone converted to the active triiodothyronine (T3) by type 1 and type 2 deiodinase enzymes (DIO1/DIO2) in peripheral tissues. T3 binds nuclear thyroid hormone receptors (TRa and TRb), forming heterodimers with retinoid X receptors (RXR) that bind thyroid response elements (TREs) in DNA, directly modulating transcription of genes controlling basal metabolic rate, thermogenesis, mitochondrial biogenesis (via PGC-1a), cardiac output, and neuronal development. T3 also exerts rapid non-genomic effects on mitochondrial respiration, ion channels, and cell membrane transport.

Dosing Protocol

Standard: Research indicates Levothyroxine (T4): 25-200 mcg daily based on TSH and free T4 levels. Liothyronine (T3): 5-25 mcg daily, often split into 2-3 doses. Combination T4/T3 ratio typically 4:1 to 3:1 when using both.

Maintenance: Research indicates titrate to TSH 0.5-2.0 mIU/L with free T4 in upper third and free T3 in mid-to-upper range. Start low (25-50 mcg T4) and increase by 12.5-25 mcg every 4-6 weeks.

Administration: oral

Timing: Levothyroxine: Take on empty stomach, 30-60 minutes before breakfast or at bedtime (3+ hours after last meal). Separate from calcium, iron, and antacids by 4 hours. Liothyronine: Split into 2-3 daily doses due to short half-life (2.5 hours for T3 vs. 6-7 days for T4).

Duration: Ongoing for diagnosed hypothyroidism. Optimization protocols may be shorter-term (3-6 months) with reassessment.

Notes

Thyroid optimization is foundational to metabolic health. CRITICAL: Always rule out adrenal insufficiency before initiating thyroid replacement — thyroid hormones increase cortisol clearance, which can precipitate adrenal crisis in undiagnosed adrenal insufficiency. Sustained-release T3 from compounding pharmacies avoids the peak/trough spikes of immediate-release liothyronine. Required bloodwork: TSH, free T4, free T3, reverse T3 (rT3), thyroid antibodies (TPO-Ab, TG-Ab) at baseline, then TSH + free T4/T3 every 6-8 weeks during titration, every 6-12 months once stable. Some optimization practitioners target TSH 0.5-2.0 with free T3 in the upper quartile of range. Medical supervision required.

Stacking

  • Selenium (supports DIO2 deiodinase conversion)
  • Zinc (cofactor for thyroid hormone synthesis)
  • Iron (required for thyroid peroxidase function)
  • Iodine (substrate for T3/T4 synthesis — only if deficient)

Interactions

  • Calcium supplements [HIGH] — Calcium chelates levothyroxine, reducing absorption by up to 50%. Separate by 4+ hours.
  • Iron supplements [HIGH] — Iron forms insoluble complexes with levothyroxine. Separate by 4+ hours.
  • Proton pump inhibitors (PPIs) [MEDIUM] — Reduced gastric acidity impairs levothyroxine absorption; may require dose increase.
  • Testosterone (all esters) [LOW] — Androgens may decrease TBG, increasing free thyroid hormone levels. May require thyroid dose adjustment.
  • Growth Hormone (Somatropin) [MEDIUM] — GH increases T4-to-T3 conversion; may unmask subclinical hypothyroidism. Check thyroid function after starting GH.

Contraindications

  • Untreated adrenal insufficiency (correct cortisol before thyroid replacement)
  • Acute myocardial infarction
  • Thyrotoxicosis
  • Known hypersensitivity to levothyroxine or liothyronine

Side Effects

  • Tachycardia and palpitations (overdose or too-rapid titration)
  • Anxiety and insomnia (particularly with T3)
  • Tremor
  • Weight loss (excessive dosing)
  • Hair loss (temporary during initiation or dose changes)
  • Heat intolerance and sweating
  • Bone density loss at suppressive doses (TSH <0.1)

Key Papers

  • 10.1089/thy.2014.0028
  • 10.1210/jc.2012-2709
  • 10.1111/cen.13422

Source Quality

FDA-approved pharmaceutical products: Levothyroxine (Synthroid, Levoxyl, Tirosint), Liothyronine (Cytomel). Brand-name preferred for levothyroxine due to narrow therapeutic index and variable generic bioequivalence. Compounding pharmacies can prepare sustained-release T3.

Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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