As many of you know, all I do is treat Hashimoto’s and over the last 4 years I have worked and spoken with over 2,000 people with Hashimoto’s.
Most of these conversations have happened during my consultations. In these, people share with me their struggles and I offer advice that helps them right away.
By far, the most common theme of these conversations is that they have normal lab results (this usually means TSH and T4 – to learn more about what are better tests to order read this post) and yet they have all the common hypothyroid symptoms.
In other words, they are fatigued, they have brain fog and memory issues, their hair is falling out, the may have depression, constipation, difficulty sleeping and muscle weakness or joint pain and more.
While researchers sometimes claim that this is rare, clinical experience and empirical data prove otherwise. I put this question to my Facebook support group on 2 occasions and over 300 people responded that they have some or all of the symptoms above and “normal” lab test results.
This situation isn’t rare, it’s very common.
And the vast majority of these people are taking some type of thyroid replacement hormone. The prescriptions vary from Synthroid to Armour to Levothyroxine and sometimes there’s some Cytomel thrown in or they’re taking Naturethroid or Tyrosint.
But often, regardless of the prescription or the dosage, they still have all the hypothyroid symptoms. And some people are over-medicated so they have hyper symptoms, as well. Like, palpitations, insomnia, tachycardia, anxiety, etc.
And after a while you have to ask: What is going on here?
It’s the same story over and over again. The medications are different, the constellation of symptoms are different, but the basic pattern is the same.
People are getting plenty of thyroid hormone, but it’s not getting into their cells and having the effect it is supposed to.
If it were, they’d have no hypothyroid symptoms. But virtually everyone does have hypothyroid symptoms.
In this post we examine why thyroid hormone conversion doesn’t happen the way it’s supposed to and what to do about it.
Let’s Review the Physiology
First of all, let’s look at basic physiology. In the body, normally, the thyroid is signaled by the pituitary with TSH (Thyroid Stimulating Hormone). The purpose of this is to goose the thyroid into producing more thyroid hormone.
This occurs because of signals from the body that it needs more. If it’s cold or you need your heart rate to increase, or your metabolism to rev up or you needs to get things moving for sex, etc.
When this happens the thyroid releases T4 (about 97%) and a little bit of T3 (do the math – yup, 3%).
And this is the basic premise of thyroid replacement hormones like Synthroid. It’s synthetic T4. The theory is that you just give it to the patient and tell them to call you in 6 months. An everything should be hunky dory.
And the reason it doesn’t work is that thyroid hormone must be converted from T4 into T3 in order for the body to utilize it. This conversion happens differently in different parts of the body.
The problem with TSH only testing to determine thyroid hormone levels in the entire body is that the pituitary, which releases TSH, converts thyroid hormone differently than the rest of the body.
This is why you often see normal TSH with lots of hypothyroid symptoms.
Many doctors, somehow, are ignorant of this fact and instead of truly understanding what is happening physiologically, blame the patient for having symptoms when their lab tests say that they should be fine.
There is an enzyme that is largely responsible for thyroid hormone conversion. It is called 5′ deodinase. And it actually comes in 3 forms: deodinase type I (D1), deodinase type II (D2)and deodinase type III (D3).
D1 converts inactive T4 to active T3 throughout the body. In the pituitary, D2 controls this conversion. These two forms behave very differently and are affected by different things.
D1 is suppressed and down-regulated (which means it decreases T4 to T3 conversion and increases reverse T3 levels) in response to stress (both physiologic and emotional), depression, dieting, weight gain and leptin resistance, insulin resistance, obesity and diabetes, inflammation from autoimmune disease or systemic illness, chronic fatigue syndrome and fibromyalgia, chronic pain, and exposure to toxins and plastics.
What did we just describe? Your average Hashimoto’s patient living in the modern world! Most people with Hashimoto’s have the majority of conditions mentioned above.
In addition, D1 activity is also lower in females, making women more prone to tissue or functional hypothyroidism.
Sound familiar? Normal lab results but hypothyroidism at the cellular level.
And when you have these conditions, there are reduced tissue levels of active thyroid hormone in all tissues except the pituitary because D2 does not behave like this, at all.
D2 is 1,000 times more efficient at converting T4 to T3 than D1 in the rest of the body. And it isn’t suppressed and down regulated by any of the things we mentioned.
So TSH is within normal range because the pituitary is getting plenty of thyroid hormone, but the rest of the body is hurtin’ for certain.
D3 converts T4 into reverse T3. There is none of it in the pituitary. D3 also competes with D1. T4 can go either way. It can be converted to T3 which the body can use or into reverse T3 which is not active.
And reverse T3 blocks the effect of T3. It blocks T3 from binding to receptors and when this happens it doesn’t work. So your metabolism slows, and D1 is suppressed so it can’t do it’s job and convert T3 to T4. And D3 blocks T3 and T4 from getting absorbed into cells.
So the result is you have low T3 levels in the cells of your body and you get all the hypothyroid symptoms.
Like most things related to Hashimoto’s the solution is not simple and it requires a multi-prong approach.
As I have said and written many times, Hashimoto’s is way more than a thyroid problem and way more than a thyroid and autoimmune problem. It is a multi-system disorder that can only be healed using a multi-system approach.
Nowhere is this more evident than in trying to fix poor thyroid hormone conversion.
There are 5 important areas that need to be assessed and addressed if you want better conversion of T4 to T3.
Let’s break it down:
1. Liver Detoxification and Other Metabolic Pathways
2. Increasing T3 and Lowering Reverse T3 Levels
3. The Gut and Thyroid Hormone Conversion
4. Adrenal Stress Can Cause Lower T3 and Higher Reverse T3
5. Systemic Inflammation Lowers T3
And as a bonus we’ll look at key nutrients that support better thyroid hormone conversion.
In the liver D1 is involved in converting T4 into T3 and selenium is an important part of this process. Reverse T3 is also broken down there.
So having enough selenium is essential. (It is recommend to take from 200 to 400 mcg. (micrograms) per day. Make sure you do not take selenium supplements that contain dairy or gluten based fillers.)
Other important factors that can prevent T4 to T3 conversion include stress (both emotional and physiological), poor nutrition, chronic illness and exposure to heavy metals like cadmium, mercury and lead.
Another important factor is lipid peroxidation and antioxidants in the liver. One of the most important in helping the body deal with the damage caused by these heavy metals and to nourish antioxidant enzyme systems is glutathione.
The best form to take orally is S-Acetyl-L-Glutathione. It can also be taken in liposomal cream form or in an IV.
In addition, there are 2 metabolic pathways in the liver that can have an impact on thyroid hormones. One such pathway is the glucoronidation pathway. This pathway is supported by B vitamins, magnesium, and glysine.
The second is sulfation. Sulfation involves binding things partially broken down in the liver with sulfur containing compounds. It is one of the major detoxification pathways for neurotransmitters, toxins, and hormones (like thyroid hormones).
Vitamin B6 and magnesium are important for sulfur amino acid metabolism, as are foods containing sulfur such as: eggs, meat, poultry, nuts and legumes. (Eggs, nuts and legumes might be a problem if you are on the Autoimmune diet.)
Lowering reverse T3 levels and increasing T3 levels is not a simple thing. There are so many variables and other factors that may hinder this process that it’s hard to offer general things that will help.
To really do this properly, one must be tested, evaluated and treated according to what results, symptoms and patterns present themselves.
That being said, let’s look at some general things that may help.
Glucoronidation, mentioned above, has been shown to degrade reverse T3.
The addition of T3 to your thyroid replacement hormone regimen may also be helpful. There are those in the thyroid community that strongly advocate T3 only treatment. Some suggest doing with natural cortisol rhythms, some with time released T3 and others with slow and deliberate increases in T3 therapy.
This may or may not work and what they fail to say is that T3 can also be toxic to the liver in high doses. Again, proper assessment and treatment is required to determine if this course of action is a good idea for you.
Elevations in cortisol, catecholamines, and some cytokines (IL-6, TNF-a, and IFN-a), and low serum albumin levels have also been associated with low T3 syndrome.
Gut bacteria is important for converting T4 into T3.
About 20 percent of T4 is converted to T3 in the GI tract, in the forms of T3 sulfate (T3S) and triidothyroacetic acid (T3AC). The conversion of T3S and T3AC into active T3 requires an enzyme called intestinal sulfatase.
Intestinal sulfatase comes from healthy gut bacteria. (Sulfur is an important nutrient for this, as well).
When you have an imbalance between good and bad bacteria in the gut, this may significantly reduce the conversion of T3S and T3AC to T3. This is one reason why people with poor gut function may have thyroid symptoms but normal lab results.
Inflammation in the gut also reduces T3 by raising cortisol. Cortisol decreases active T3 levels while increasing levels of inactive T3.
Studies have also shown that cell walls of intestinal bacteria, called lipopolysaccharides (LPS), negatively effect thyroid metabolism in several important ways.
• reduce thyroid hormone levels;
• dull thyroid hormone receptor sites;
• increase amounts of reverse T3;
• decrease TSH; and
• promote autoimmune thyroid disease (AITD).
With stress, cortisol levels often go up. The increased cortisol levels contribute to this disconnect in the body between the TSH and peripheral tissue T3 levels.
Stress reduces T3 levels in the tissues and increases reverse T3 and this results in tissue hypothyroidism and potential weight gain, fatigue, and depression.
This vicious cycle of weight gain, fatigue, and depression that is associated with stress may be prevented with supplementation with timed-released T3 according to some studies.
The reduced immunity from chronic stress has also been thought to be due to excess cortisol production; but the associated reduction in tissue thyroid levels are shown to play a larger role in the decreased immunity seen with stress.
As with stress, treatment with prednisone or other glucocorticoid will suppress D1 and stimulate D3, reducing T4 to T3 conversion and increasing T4 to reverse T3, causing a relative tissue hypothyroidism that is not detected by TSH testing.
This low cellular thyroid level certainly contributes to the weight gain and other associated side-effects with such treatment. Thus, in stressed patients or those treated with corticosteroids, there are reduced tissue T3 levels that are not reflected by the TSH level, making the TSH an inappropriate marker for tissue levels of T3.
So making sure that you have proper levels of DHEA and cortisol is very important.
As is changing the things in your life that cause you stress. With Hashimoto’s we have emptied our stress savings accounts. We have so much physiologic stress that added emotional stress is incredibly destructive. And one area, in particular, is in the impact of stress on tissue levels of T3.
Hashimoto’s is, at it’s root, a disease of inflammation. And research has found that the inflammatory immune cells (cytokines) and proteins like IL-1, Il-6, C-reactive protein (CRP), and TNF-alpha will significantly decrease D1 activity and reduce tissue T3 levels. Any person with an inflammatory condition – Hashimoto’s – will have a decreased T4 to T3 conversion in the body and a relative tissue hypothyroidism.
These immune proteins will, however, increase the activity of D2 and suppress the TSH despite reduced peripheral T3 levels; again, making a normal TSH an unreliable indicator of normal tissue thyroid levels.
There is also a direct inverse correlation between CRP and reduced tissue T3, so individuals with elevated CRP (greater than 3 mg/l) or other inflammatory cytokines may have a significant reduction in cellular T3 levels.
The suppression of T3 levels inside the cells is linked with the degree of elevation of CRP, despite serum thyroid tests being “normal”.
So, if any inflammation is present, the body will have lower T3 levels in the cells and this can impact function; but the pituitary will have increased levels of T3, resulting in a lowering of the TSH so that, once again test results appear normal. (Have I made this point enough times?)
This really emphasizes the importance of anti-inflammatory strategies to improve T3 levels in the tissues. Anti-inflammatories like Turmeric, ginger, resveratrol, glutathione, and Vitamin D are all helpful.
Sometimes these are needed in rather high dosages.
Eliminating foods that cause inflammation is also absolutely critical: gluten, dairy, soy, sugar, alcohol, processed foods, pesticides and chemical additives should all be strictly eliminated.
The Autoimmune Paleo approach is an excellent diet for reducing systemic inflammation and increasing tissue T3 levels.
Commiphora muku guggulu (Myrrh resin) Guggul produces a resinous sap known as gum guggul. The extract of this gum, called gugulipid, guggulipid or guglipid, has been used in Ayurvedic medicine, a for nearly 3,000 years in India. The active ingredient in the extract is the steroid guggulsterone. This has been shown to stimulate healthy synthesis of T3.
Selenium is a major cofactor for the enzyme 5′ deiodinase which is responsible for converting T4 into T3 as well as degrading reverse T3.
Low zinc status has been shown to compromise T3 production. Zinc can improve thyroid hormone production and play a role in reducing antibodies.
Lipid peroxidation and antioxidant enzyme systems have been shown to play a profound role peripheral thyroid hormone conversion. Glutathione is extremely effective in supporting peroxidation.
Lastly, it is essential to work with someone who understands the complexity of this situation and who can evaluate what is going on properly and who can determine which course of action and combination of things may be best for you.
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So now, not only is it my profession, it’s my passion, and it’s personal. I’ve been joking with people lately saying it’s a blessing and a curse. A blessing because I really get it, and a curse because I really got it! ?