#373 – Thyroid function and hypothyroidism: why current diagnosis and treatment fall short for many, and how new approaches are transforming care | Antonio Bianco, M.D., Ph.D.

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Nov 17, 2025

Dr. Antonio Bianco, a renowned physician-scientist and former President of the American Thyroid Association, dives deep into thyroid physiology. He discusses the complex roles of deiodinase enzymes in regulating thyroid hormones and their implications for patient care. The conversation highlights the inadequacy of conventional TSH testing, the impact of genetics on thyroid function, and the ongoing debates over treatment methods for hypothyroidism. Bianco also shares insights into why patients may feel unwell despite 'normal' lab results and the need for personalized treatment approaches.

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INSIGHT

T4 Is A Prohormone Controlled Locally

The thyroid produces T4 as a long-lived prohormone and tissues convert it to active T3 locally.
This preserves iodine and lets each tissue control thyroid action via local conversion.

INSIGHT

Deiodinases Set Tissue Thyroid Tone

Deiodinases direct T4 toward activation (T3) or inactivation (reverse T3), changing tissue thyroid signaling.
Reverse T3 is essentially inactive and represents an inactivation pathway, not a competing agonist.

INSIGHT

Fasting Rewires Deiodinase Activity

Fasting shifts deiodinase activity: body lowers T3 and raises reverse T3 to conserve energy.
Liver D1 activity falls with low insulin/carbs, reducing reverse T3 clearance and amplifying the shift.

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Antonio Bianco is a world-renowned physician-scientist and expert in thyroid physiology and metabolism. In this episode, Antonio explores the complex biology of thyroid hormone production, conversion, and regulation—highlighting how deiodinase enzymes modulate hormone activity at the tissue level and why that matters for interpreting lab results. He discusses the shortcomings of relying solely on TSH as a marker of thyroid function, the ongoing debate around combination therapy with T3 and T4 versus standard T4 treatment, and how genetics, tissue sensitivity, and individual variability influence thyroid hormone metabolism. The conversation also examines how hypothyroidism affects energy, mood, cognition, and longevity; why some patients remain symptomatic despite "normal" labs; and how future research could reshape treatment paradigms.

We discuss:

How the thyroid produces, stores, and activates hormones like T4 and T3 to finely regulate thyroid activity [2:45];
How fasting alters thyroid hormones to conserve energy [12:45];
Action of the deiodinases: how D1, D2, and D3 enzymes control the activation and inactivation of thyroid hormones [19:15];
The normal function of thyroid hormone and the roles of the hypothalamus, pituitary gland, and deiodinases in maintaining hormonal balance [23:30];
Why understanding thyroid physiology is essential for proper diagnosis and treatment of hypothyroidism [33:45];
Testing for thyroid hormones: understanding free vs. total levels, the limitations of current T3 assays, best practices, and more [36:00];
Genetic and sex-based variability in thyroid hormone regulation and their limited clinical significance [43:45];
Hyperthyroidism: causes, symptoms, diagnosis, and treatment options [46:00];
Hypothyroidism: diagnosis and autoimmune causes of hypothyroidism [56:30];
More on hypothyroidism: diagnostic biomarkers, antibody patterns, and non-autoimmune presentations [1:05:00];
Thyroid hormone replacement therapy [1:15:15];
More on thyroid replacement strategies: exploring the evidence gaps, mortality signals, effects on lipids, and more [1:28:00];
Hypothyroidism basics: causes, antibody implications (including pregnancy), and how to make the diagnosis before choosing therapy [1:35:15];
Thyroid medication: compounded controlled-release T3, brand name versus generic, and what Antonio prescribes to newly diagnosed hypothyroid patients [1:42:45];
Redefining treatment success: why normalizing TSH isn't always enough for patients with hypothyroidism [1:54:45];
Case studies: analysis of two unusual cases of thyroid disease [1:57:00];
Dangers of supplementing with high levels of iodine, and female-specific risk of thyroid disease [2:05:45];
Case study of a patient who presents with elevated TSH but no symptoms [2:09:30];
How future research could reshape treatment, and Antonio's new book called "Rethinking Hypothyroidism" [2:13:15]; and
More.

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