#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.

Understanding the thyroid gland’s biology and physiology is essential to comprehend how it uses dietary iodine to produce hormones that are critical for regulating the body's metabolism.

Thyroid Uses Dietary Iodine to Produce Hormones

The thyroid gland utilizes dietary iodine to synthesize hormones that are pivotal for metabolic processes throughout the body.

Thyroid Traps Iodine, Creates Inactive T4 With Four Iodine Atoms

Antonio Bianco explains that the thyroid traps iodine from blood intake, which is crucial for thyroid hormone production. Without iodine, the gland cannot produce thyroid hormones. The thyroid synthesizes mainly T4, an inactive hormone containing four iodine atoms, which serves as a large storage pool for thyroid hormone.

Deiodinases Convert T4 To Active T3, Activating Thyroid Receptors

Bianco's research highlights the role of deiodinases, enzymes that activate or deactivate thyroid hormones at the tissue level. T4 serves primarily as a prohormone before being converted into active T3 by deiodinases, allowing T3 to bind effectively to cell and tissue receptors. Brown fat tissue can amplify T3 levels significantly in mere hours via type 2 deiodinase, but this surge is strictly localized to the tissue and is fundamental for its energy utilization.

Producing T4 Storage and Converting To Active T3 Preserves Iodine

The preservation of iodine is a critical aspect of thyroid hormone production due to evolutionary pressure from iodine deficiency. Thanks to an efficient recycling system, once an iodine atom is removed from T4 to activate it into T3, this iodine is not lost but reclaimed.

T4's 8-Day, T3's 12-hour Half-Lives Enable Precise Thyroid Regulation

The differing half-lives of thyroid hormones permit precise regulation of the gland's activities and hormone distribution in the body.

Deiodinases Convert T4 to Reverse T3, Controlling Thyroid Action

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Understanding the various causes of thyroid disorders is crucial for diagnosis and treatment. Dr. Antonio Bianco delves into the reasons behind hyperthyroidism and hypothyroidism, two primary disorders of the thyroid gland.

Causes of Hyperthyroidism: Graves' Disease or Thyroid Nodules

Hyperthyroidism results from an overactive thyroid, where the gland produces an excess of hormones.

Graves' Disease Is Caused by Antibodies That Overstimulate Thyroid Hormone Production

Graves' disease is an autoimmune condition where antibodies bind to the thyroid gland as if they were thyroid-stimulating hormone (TSH), pushing the gland into overdrive. The thyroid gland grows homogeneously and produces high levels of thyroid hormones T4 and T3. This leads to tissues in the body experiencing hormone levels up to three times higher than stable levels.

Nodules May Autonomously Produce Excess Thyroid Hormone

Thyroid nodules, solitary or as part of a multinodular goiter, can independently begin overproducing thyroid hormone. Iodine-induced hyperthyroidism can occur in individuals with a thyroid nodule when there’s an excess intake of iodine.

Hypothyroidism: Commonly Caused by Autoimmune Thyroid Destruction (Hashimoto's Thyroiditis)

Hypothyroidism occurs when the thyroid does not produce enough hormones, often due to an autoimmune attack known as Hashimoto's disease.

Hypothyroidism Causes: Thyroid Removal, Radiation Damage, Congenital Defects

Bianco explains the most common cause of hypothyroidism is Hashimoto’s disease, where the immune system doesn't recognize the thyroid as part of the self and attacks it, leading to reduced thyroid function and size. However, there are other causes of hypothyroidism, including surgical removal of the thyroid, radioactive iodine treatment, and congenital defects. In fact, congenital hypothyroidism occurs in about one in every 2,500 to 3,000 live births.

Treatment often focuses on thyroid replacement therapy instead of the underlying autoimmunity. However, studies show that selenium, vitamin D, and other antioxidants may help reduce thyroid peroxidase (TPO) antibody levels, slowing down the autoimmune attack.

Finally, in some cases, the immune system's stimulation and subsequent destruction of the thyroid tissue can lead to hypothyroidism years after initial treatment, su ...

Peter Attia and Antonio Bianco delve into the nuances of diagnosing thyroid disorders, emphasizing the need for a comprehensive approach that looks beyond traditional test results.

Diagnostic Approach: Measure TSH, Free T4, Sometimes Free T3

In clinical settings, TSH and free T4 are the standard measurements used to diagnose thyroid conditions. However, Antonio Bianco criticizes this approach as inadequate and emphasizes the importance of also measuring T3, the biologically active hormone. Despite the challenges of measuring T3, such as the high inter-assay variability, Bianco suggests it is essential for a complete understanding of thyroid physiology.

Elevated TSH With Low Free T4 Indicates Hypothyroidism; Low TSH With High Free T4 Indicates Hyperthyroidism

An increased TSH, typically used as a routine test for detecting hypothyroidism even before symptoms develop, in combination with reduced free T4 levels, is a clear indicator of primary hypothyroidism. On the other hand, low TSH with elevated free T4 and T3 levels suggests hyperthyroidism, such as Graves' disease. Bianco also brings up secondary hypothyroidism, where a low free T4 is observed without an elevated TSH.

Peter Attia cites a case where the abnormality lay in the TSH, which did not correspond with the free T4 and free T3 levels.

Measuring TPO Antibodies Can Identify Autoimmune Thyroid Disorders

TPO antibodies are indicators of autoimmune thyroid disorders, such as Hashimoto's disease, and can also have implications in pregnancy, where high levels are associated with an increased risk of miscarriage and prematurity.

Thyroid Test Interpretation Is Complex; TSH May Not Reflect Tissue-Level Activity

Peter Attia discusses the complex interpretation of thyroid tests, heightened by the fact that TSH levels, which are typically used to diagnose thyroid disorders, do not always accurately reflect the thyroid hormone activity at the tissue level. Antonio Bianco highlights the importance of looking beyond TSH, considering the free T4 and T3 levels, especially when TSH measurements might be confounded by interfering substances like aggregated TSH molecules.

T3/Rt3 Ratio Reveals Deiodinase Activity and Thyroid Metabolism

To get a clearer picture of thyroid function, the ratio of free T3 to reverse T3 can be a useful surrogate for deiodinase activity, which is not directly measurable through blood tests. Bianco states that reverse T3 is a more reliable measure because it remains stable for a few hours and directly reflects the immediate metabolism of T4. The T3 to r ...

Thyroid disorders can affect the body's metabolic processes dramatically, and treatment options must be carefully considered to manage their impact effectively.

[restricted term] Treats Hypothyroidism By Normalizing Tsh

[restricted term] is the standard treatment for hypothyroidism, where the body is given the thyroid hormone that the damaged thyroid is no longer producing, effectively turning the damaged gland atrophic. The goal of therapy, as per the guidelines by professional societies, is to normalize TSH (thyroid-stimulating hormone). However, physicians tend to focus less on symptoms and aim to achieve biochemical euthyroidism, rather than clinical euthyroidism.

[restricted term]: Effective Treatment for Most Patients

Antonio Bianco highlights that [restricted term], which contains T4, is effective in most cases. However, Bianco emphasizes the goal of normalizing TSH, as not all patients can achieve clinical euthyroidism, indicating that even when TSH is normalized, a patient may still exhibit symptoms.

Patients Experience Symptoms Despite "Normal" Tsh on [restricted term]

Despite its effectiveness, some patients on [restricted term] with "normal" TSH levels continue to experience symptoms, such as brain fog or lack of energy even after thyroid removal surgery. Peter Attia describes a patient who felt worse on [restricted term] ([restricted term]) despite a reduced TSH level. Bianco acknowledges that [restricted term] does not address all patient issues, and some patients still experience higher mortality rates compared to control populations.

T4 and T3 Combination Therapy as a Preferred Alternative

For patients who do not respond well to [restricted term] alone, practitioners might consider combination therapy with T4 and T3 after other comorbidities have been ruled out. Bianco believes a synthetic combination of T4 and T3 can be as effective as desiccated thyroid extract, with studies suggesting a ratio of around 4:1 as optimal, mirroring the ratio in desiccated thyroid extract.

Desiccated Thyroid Extracts With T4 and T3 Face Quality and Consistency Debates

Desiccated thyroid extract, containing both T4 and T3, faces debates surrounding its quality and consistency, as it was grandfathered in without explicit FDA approval for treating hypothyroidism. The potency has since been standardized, and studies indicate that it has a similar safety profile as [restricted term]. Patients often prefer combination therapy, and when blinded, choose desiccated thyroid extract over [restricted term] alone.

Compounded Time-Release T3: Investigational Status, Uncertain Pharmacokinetics and Efficacy

The challenge with desiccated thyroid extract, which contains T3, is its short half-life and the resulting T3 spik ...

The medical field is grappling with the complexities of thyroid disease management, presented here through the insights of Antonio Bianco and Peter Attia, who raise concerns over treatment efficacy, proper diagnosis, and emerging technologies.

Hypothyroidism: Risk Factor for Cardiovascular Disease

Antonio Bianco considers hypothyroidism to be a significant risk factor for cardiometabolic diseases.

[restricted term] May Not Fully Normalize Cholesterol, Indicating Incomplete Thyroid Function Restoration

Bianco comments that patients treated with [restricted term] often require statins because [restricted term] may not restore full thyroid function, especially in the liver, as evidenced by their unimproved cholesterol levels despite normalized TSH.

[restricted term]-Treated Hypothyroid Patients Have Higher Mortality Than General Population

Bianco points out that the mortality rate is 2.5 times higher for hypothyroid patients treated with [restricted term] compared to the general population. He also notes that combining T4 with T3 therapy may reduce mortality by 30%, showcasing a potential issue with the effectiveness of current [restricted term] treatment.

Debate on Diagnostic Thresholds and Treatment Targets for Mild Thyroid Abnormalities

Controversy surrounds the diagnostic thresholds and treatment targets for thyroid abnormalities.

Aging Raises the "Normal" TSH Upper Limit, Complicating Interpretation

Bianco brings to light that 'normal' TSH levels increase with age, suggesting that what is considered a 'normal' TSH can change, making diagnosis and treatment more complex, particularly among the elderly. This introduces challenges for providers in deciding whether elevation of TSH should prompt [restricted term] treatment.

Thyroid Dysfunction Symptoms Overlap With Other Conditions, Complicating Diagnosis

The symptoms of thyroid dysfunction can be easily mistaken for other conditions, making accurate diagnosis difficult. Attia and Bianco's discussion implies that personalized patient history and consistent testing methods are crucial for accurate diagnosis.

Future Research and New Treatments May Address Current Thyroid Therapy Limitations

Emergent technologies and treatments may revolutionize how thyroid disorders are managed.

Emerging Tech: Mass Spectrometry T3 Assays and Sustained-Release T3 Formulations Under Investigation

Attia and Bianco discuss the potential of Mass Spectrometry (MassPAC) for T3 assays, especially ...