T4 to T3 Conversion Deficit Hypothyroidism

This is the third post in my series on women and hypothyroidism. If you’re new here, I recommend starting with the first post on hypothyroidism to build your understanding. Hopefully, you’ve also read the last post on essential thyroid nutrients, as that’s foundational for all types of hypothyroidism.

What is T4 to T3 Conversion Deficit Hypothyroidism?

In this post, we focus on a specific type of hypothyroidism called T4 to T3 conversion deficit. This occurs when your thyroid gland can produce T4, but your body struggles to convert it into T3, the active hormone your cells need. This conversion relies on specific enzymes, called deiodinases. If your body isn’t converting T4 to T3 properly, you may experience hypothyroid symptoms even though your thyroid gland itself appears to be functioning well.

Understanding Deiodinase Enzymes for T4 to T3 Conversion

• Deiodinase Type 1 (D1): Converts T4 into T3 in most tissues of the body, except for the pituitary gland.
• Deiodinase Type 2 (D2): Highly efficient at converting T4 into T3 in the pituitary gland, resulting in higher T3 levels there compared to the rest of the body.
• Deiodinase Type 3 (D3): Converts T4 into reverse T3 (rT3), which is inactive and competes with T3 for receptor sites, effectively blocking T3’s action in your cells.

Since the pituitary gland doesn’t produce D3, TSH levels can appear normal, even when your body is starved for T3. This explains why TSH isn’t always the best marker for diagnosing whole-body hypothyroidism.

Why Should You Test T4 to T3 Conversion?

If you have a T4 to T3 conversion problem, T4 hormone replacement therapies (like Synthroid or levothyroxine) may not be effective for your hypothyroidism. In these cases, a T3-only approach may work better, and hormone replacement might only be needed temporarily—or not at all—if the thyroid gland is healthy and the conversion issue can be resolved.

How to Identify a T4 to T3 Conversion Deficit

Common signs of a conversion deficit include:

• TSH levels: Normal or slightly elevated.
• T4 levels: Usually within normal ranges.
• Free T3 levels: May be low or within normal ranges.
• Reverse T3 (rT3) levels: often elevated; this is one of the most important markers for this type of hypothyroidism.
• T3 to rT3 ratio: Typically low (below 20).

Even if your thyroid labs appear “normal,” you may still experience symptoms of hypothyroidism. This is where functional medicine comes in—by assessing deeper imbalances, such as enzyme dysfunction.

What Causes Poor T4 to T3 Conversion?

Several factors can impair the enzymes responsible for converting T4 to T3. Here are some common causes:

• Chronic Stress and Cortisol: Long-term stress increases cortisol levels, which reduces active T3 and disrupts the hypothalamic-pituitary-adrenal (HPA) axis.
• Depression and Bipolar Disorder: Many individuals with depression or bipolar disorder have underlying thyroid dysfunction. Studies show that T3 therapy can outperform traditional medications in treating these conditions.
• Chronic Pain: Persistent pain lowers D1 and D2 enzyme activity, leading to tissue-level hypothyroidism. Some pain specialists recommend T3 supplementation to manage these cases.
• Calorie Restriction or Dieting: Low-calorie diets can reduce cellular T3 by up to 50%, slowing your basal metabolic rate (BMR) by 15-40%. Prolonged dieting may cause long-term damage to your thyroid function and make weight loss difficult.
• Insulin Resistance, Diabetes, and Obesity: These metabolic issues impair T4 to T3 conversion. For individuals with these conditions, T4 therapy alone may not be effective, and T3 may be necessary.
• Leptin Resistance: Many overweight women experience leptin resistance, which can lead to low cellular T3 levels and hinder weight loss.
• Excessive Exercise: Over-exercising, particularly in combination with dieting, can increase reverse T3 and lower T3 conversion, negating the benefits of exercise.
• Iron Deficiency: Low iron levels impair T4 to T3 conversion and increase reverse T3 levels. For optimal thyroid function, iron saturation should be above 25, and ferritin should be at least 70.
• Inflammation: Chronic inflammation—from stress, obesity, infections, autoimmune diseases, or menopause—reduces D1 activity, leading to low tissue T3 levels.
• Environmental Toxins: Plastics, pesticides, mercury, and other toxins disrupt thyroid receptors and impair T4 to T3 conversion.

How to Address T4 to T3 Conversion Issues

In personalized functional medicine, we don’t just treat thyroid hormone imbalances by prescribing medication. Instead, we identify the root causes of conversion deficits and address them. This could involve managing stress, improving diet, or using a detox program. Each of our patients requires an individualized precision medicine approach.

Need help with your thyroid? Please contact us directly, or send your questions my way below!