The Thyroid T4 to T3 Conversion Story

This is the third post on women and hypothyroidism. If you like, start with the first post. Hopefully, you read the last post on thyroid nutrients, as this is important for all types of hypothyroidism.

Thyroid hormone conversion deficits

Here I focus on a functional type of hypothyroidism: T4 to T3 conversion deficits. In this situation, your thyroid gland is often functional. It’s able to produce T4. The problem is that your T4 is not properly converted into active/free T3, which is what your peripheral tissues and cells use. You need enzymes for this conversion, called the deiodinase enzymes. I briefly describe the function of these enzymes, for those of you who like to know the physiology. If your eyes glaze over, skip to the next section.

There are three types of deiodinase enzymes:

Deiodinase Type 1 (D1)

This enzyme converts T4 into T3 throughout your whole body, except for your pituitary gland.

Deiodinase Type 2 (D2)

D2 converts T4 into active T3 only in your pituitary gland. It’s about 1,000 times more efficient than D1. This means that 80-90% of T4 in your pituitary gland gets converted to active T3, but in your tissues and cells it’s only 40-50%.

Deiodinase Type 3 (D3)

D3 converts T4 into inactive (junk) reverse T3 (rT3). RT3 takes up receptor sites for active T3. In other words, it blocks active T3. D3 competes with D1. This is why we measure rT3.

There is no D3 in your pituitary gland. This is yet another reason why T3 levels are higher in your pituitary. Since the signals to make thyroid hormone (TSH) come from your pituitary, TSH can be normal according to your pituitary gland, but not an accurate marker for whole body hypothyroidism.

Why assess T4 to T3 conversion?

If you are hypothyroid because of a conversion problem, then T4 hormone replacement medication may not be appropriate. You may be a case for a T3-only approach, while you address underlying causes of your conversion problem. Hormone replacement may not be necessary or be temporary. If there’s nothing wrong with your thyroid gland, then it is completely possible to not be on thyroid hormone replacement permanently.

How do you determine if you have conversion deficits?

  1. You have hypothyroid symptoms.
  2. Your labs fit one of the following scenarios…

Conversion deficit labs look like this:

  • TSH levels can be normal or elevated.
  • T4 levels are typically fine.
  • Free/active T3 levels can be low, or normal.
  • Reverse T3 (rT3) levels may be high.
  • The ratio between free T3 and rT3 may be low (under 20).
  • Often all thyroid labs are normal!

When your D-enzymes are out of whack

When D1 is blocked, D3 is increased, and D2 is up-regulated, it’s the perfect storm for tissue hypothyroidism. In functional medicine, we find which of these factors is the cause, and work to resolve it. We don’t just offer thyroid hormones and call it a day.


Chronic stress raises your cortisol. Elevated cortisol lowers active T3.  Chronically elevated cortisol disrupts your brain-adrenal communication, otherwise known as your HPA axis.


Many depressed and bipolar patients have thyroid dysfunction as a contributor to their depression. In this study, T3 therapy was more effective than 14 other medications to treat bipolar disorder, and the same was found in the STAR*D Report for depression.


Pain disrupts D1 and D2, and causes tissue and cellular hypothyroidism. These pain specialists understand this and recommend T3 supplementation to patients with significant pain.What to do: Consider using T3 or a thyroid glandular like Thyrotain

Reduced Calorie Dieting

Acute or chronic dieting lowers your cellular T3 levels by up to 50%. This reduces your basal metabolic rate (number of calories burned per day) by 15-40%. After chronic dieting, your thyroid levels and metabolism often do not return to normal levels. Your body can stay in starvation mode for years, making it very difficult to lose weight, or maintain lost weight.

Insulin resistance/diabetes/metabolic syndrome/obesity

Insulin resistance, diabetes, and metabolic syndrome reduce T4 to T3 conversion. These are cases in which T4 supplementation alone may not be effective. T3 alone could help.


Leptin regulates your weight and metabolism. You secrete leptin when you gain weight, to signal your brain (hypothalamus) that you have enough energy (fat) stores. Your hypothalamus should then reduce your hunger, increase your satiety, boost your resting metabolism, and increase fat breakdown. Research shows that leptin signaling is dysfunctional in the majority of women who can’t lose weight.

The majority of overweight women are able to produce leptin; however, they have leptin resistance. Your brain senses leptin resistance as starvation, and causes you to increase fat stores, rather than burn excess fat. Leptin resistance results in low cellular T3.


Women who perform excessive exercise, especially while dieting, have reduced T4 to T3 conversion, and increased rT3, which counteracts the positive effects of exercise.

Iron deficiency

Iron deficiency can reduce T4 to T3 conversion, increase reverse T3 levels, and block the metabolism boosting properties of thyroid hormone. Low iron (iron saturation below 25, or ferritin below 70), can result in low cellular T3 levels.


Inflammation decreases D1 activity and reduces tissue T3 levels. This includes inflammation from physical or emotional stress, obesity, diabetes, depression, menopause, heart disease, autoimmune disease, injury, chronic infections, and cancer.

Environmental toxins

Numerous toxins, including plastics, pesticides, mercury, and flame retardants, block tissue thyroid receptors and reduce T4 to T3 conversion.

You may be interested in learning about Hashimoto’s, or how your thyroid affects fertility and periods, and hypothyroidism in pregnancy.

Need help with your thyroid? Please reach out!

Send questions or comments my way below,

paris healing arts, doctor laura paris, dr. laura paris, dr laura paris

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  1. Is it possible that a long-term, chronic infection like SIBO ( small intestine bacterial overgrowth) or having parasites could cause poor T4 to T3 conversion? Would the chronic inflammation from these infections affect T4-T3 conversion?

    1. There’s a myriad of ways that inflammation from a gut infection or overgrowth could affect thyroid hormone conversion, sure.

  2. Hi,
    Thank you so much for all the detailed explanations of hypothyroidism. I’ve just learned a lot. I was diagnosed with Hashimoto’s about 6 years ago and currently on Levothyroxin. Something tells me the medication isn’t working right; i struggle with chronic iron deficiency, inflammation and pain in the knees, hip, constipation, brain fog, always tired, high heart rate, increasing sugar in the blood,… At times I feel like my body is giving up on me, but my doctor says that my lab tests are normal so we never changed the treatment or even the dose of the meds I take. I am definitely going to have the T4 conversion into T3 looked into . what else should i do?

  3. Hi Laura
    Ten years ago my cortisol was out of sync (high at night and low in the morning) and I was not converting T4 to T3. I was very lethargic and unwell and I was prescribed Naturethroid by a naturopath. I did well on 1.5 grains per day since then. Last year I eventually got rid of the excessive stress by retiring. Two years ago I lost 20lbs on the keto way of eating. I worked on healing a leaky gut and insulin resistance. I am no longer pre-diabetic. Last year I maintained my weight on low carb/keto. A year ago I started becoming intolerant to heat, followed by insomnia and eventually an Afib attack a few months ago. I left a warm climate (Hawaii) and returned to my home country of Scotland one year ago. I expected to be cold and I wasn’t. My Doctor in Scotland wouldn’t prescribe Naturethroid so I sourced from USA. I was given no blood tests as I was not following their preferred recommendation of Levothyroxine.
    I am currently in Hawaii visiting my daughter for three month vacation so went to my doctor and asked for blood tests which showed TSH 0.16, Free T4 0.9 and Free T3 2.6. Dr has said I am over medicated and shouldn’t be taking any T3 as it is spiking my heart issues (I have severely calcified arteries). After allowing me to take Naturethroid for all these years she is now prescribing Levothyroxine. My question is, is it possible to heal the T4 to T3 conversion with all I have been doing? If I can now convert is it possible that I may not need T4 either? I have started on Levothyroxine a week ago and am a bit tired and my heartbeat has slowed to high 50’s (used to be around 75. I am assuming there will be a transition period. Would appreciate your insight. Thank you.

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