🦋 T4-to-T3 Conversion & Reverse T3 Simulator

Baseline T4-to-T3 Conversion in Peripheral Tissues

Healthy thyroid hormone conversion, explained briefly.

• ~100 µg: Daily T4 secretion (thyroid gland output)
• ~80%: T4 converted to T3 (via peripheral deiodinases)
• High: D1/D2 activity (normal resting state)
• 80%: Circulating T3 source (from peripheral conversion)

Thyroxine release and peripheral activation

T4 is the main thyroid hormone released into blood.

It is largely a prohormone, activated in tissues.

D1 and D2 deiodinase enzymes

D1 acts mainly in liver and kidney.

D2 acts in brain, pituitary, and muscle.

Normal T3:rT3 balance

Active T3 dominates over inactive reverse T3.

This ratio reflects healthy metabolic tone.

Baseline conversion favors active hormone by design.

A Physiological Stressor Enters the System

Illness, fasting, or surgery trigger early adaptation.

• 4+: Common triggers (illness, fasting, surgery, trauma)
• Elevated: Cortisol response (stress hormone rises)
• Mild dip: Early T3 change (small initial decline)
• Stable: T4 level (still near-normal early on)

What counts as a stressor

Severe illness, fasting, and major surgery all qualify.

Critical illness produces the strongest signal.

Early hormonal signaling changes

Cytokines and cortisol rise with stress severity.

These molecules influence deiodinase gene expression.

Why the body responds this way

Lowering metabolism conserves energy during crisis.

This is an adaptive, not pathological, first step.

Stress signaling begins to nudge conversion enzymes.

D1/D2 Decline While D3 Activity Rises

The enzyme population driving conversion begins to change.

• ↓ Falling: D1/D2 activity change (active pathway suppressed)
• ↑ Rising: D3 activity change (inactive pathway induced)
• Low: D3 normal expression (mainly fetal/placental tissue)
• Cytokines: D3 induction trigger (illness-driven upregulation)

D3 deiodinase and reverse T3

D3 converts T4 into inactive reverse T3.

It also degrades active T3 directly.

Suppression of the active pathway

D1/D2 expression and activity are downregulated.

Less T4 is routed toward active T3.

A competing-enzyme system

D1/D2 and D3 compete for the same T4 pool.

Their shifting ratio decides hormone output.

Enzyme balance, not T4 supply, now drives outcome.

Conversion Increasingly Favors Reverse T3

As stress deepens, output tilts further toward rT3.

• Declining: T3 output trend (with stress severity)
• Rising: rT3 output trend (with stress severity)
• Dose-linked: Severity dependence (worse illness, bigger shift)
• Additive: Fasting contribution (compounds illness effect)

Severity-dependent conversion shift

Mild stress causes a small shift in balance.

Critical illness causes a dramatic shift.

Fasting compounds the illness signal

Prolonged fasting independently favors D3 activity.

Combined stressors amplify the rT3 shift.

Stream thickness reflects flow share

More T4 molecules are captured by D3 enzymes.

The active T3 output stream visibly thins.

Output streams visualize the shifting flow split.

Euthyroid Sick Syndrome — The Adaptive Pattern

Low T3, high rT3, near-normal T4 — usually not disease.

• Normal/low: T4 level (often near-normal range)
• Low: T3 level (reduced active hormone)
• Elevated: Reverse T3 (hallmark lab finding)
• Usually none: Treatment need (resolves as illness resolves)

The classic lab pattern

Low T3 with elevated rT3 and near-normal T4.

This combination defines the syndrome.

Mistaken for hypothyroidism

Symptoms can resemble low thyroid function.

TSH is often normal, unlike true hypothyroidism.

A protective, not harmful, response

Lower metabolic rate conserves resources in illness.

Pattern typically reverses once illness resolves.

Treating the underlying illness resolves the pattern.