373 – Thyroid function & hypothyroidism: how new approaches are transforming care — Key Takeaways
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373 – Thyroid function & hypothyroidism: how new approaches are transforming care
Peter Attia MD2h 34mNov 17, 2025
Watch the originalMortality is 2.5x higher in hypothyroid patients treated with levothyroxine than in controls — a finding just published by the speaker — raising urgent questions about whether T4 monotherapy is sufficient or whether the underlying disease drives excess mortality.
Key takeaways
Tissue T3 can spike 10x with zero change in blood T3
Tissue T3 can spike 10x with zero change in blood T3
- Cold-exposed rats showed 10x T3 increase in brown fat within 24h; blood T3 unchanged. D2 knockout eliminated the heat response.
- Same local D2 conversion mechanism governs brain T3 — most cerebral T3 is produced locally, not delivered from circulation.
D1 clears reverse T3; low insulin/carbs suppresses D1, letting rT3 accumulate
D1 clears reverse T3; low insulin/carbs suppresses D1, letting rT3 accumulate
- D1 is richly expressed in liver and highly sensitive to insulin and carbohydrate intake — fasting drops D1 activity.
- Result: rT3 rises from both increased production (T4→rT3 via D3) and decreased clearance simultaneously.
T3 immunoassays are clinically unreliable; mass spec required for accuracy
T3 immunoassays are clinically unreliable; mass spec required for accuracy
- At T3 levels ~90-100 ng/dL, immunoassay and mass spec curves diverge significantly — immunoassay becomes noise.
- Reverse T3 immunoassay is worse: four different commercial assays run on the same sample produced completely inconsistent results.
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In this video
- 1mIntroduction and Overview of Thyroid Physiology
- 10mT4, T3, and the Deiodinase System
- 30mFasting, Reverse T3, and Metabolic Adaptation
- 47mHypothalamic-Pituitary-Thyroid Axis and TSH Regulation
- 1h 3mLab Testing: Free vs. Total Hormones, Assay Limitations
- 1h 20mHyperthyroidism: Causes, Diagnosis, and Treatment Options
- 1h 43mHypothyroidism: Causes, Hashimoto's, and Autoimmunity
- 2h 3mThyroid Replacement Therapy: Levothyroxine vs. Desiccated Thyroid
“Mortality is 2.5 greater in the patients taking levothyroxine with hypothyroidism. We just published that.”
— Tony
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