Hashimoto’s: Why Do I Feel Like Crap on Synthroid?

The Tyranny of T4 Supplementation and TSH Only Testing for Hashimoto’s

Hashimoto’s is one of the most common autoimmune diseases in the US. It is routinely undiagnosed or under-diagnosed and when it is treated, the gold standard of treatment is to give patients Synthroid or Levothyroxine (Synthetic T4).

To monitor whether or not this is working most doctors periodically test TSH.

This approach often does not work and, more importantly, millions of women and men with Hashimoto’s who are being treated this way do not feel any better, or feel better for a period of time, then end up feeling really lousy.

They wind up feeling all the symptoms of hypothyroidism like being tired all the time, they can’t lose weight, they have lots of joint and muscle pain, they suffer from brain fog, anxiety and depression, their hair falls out, they feel cold, they have no sex drive and their lives become miserable.

And many of them have blood test results that look normal.

In this post I will examine why TSH is not a good measure of whether or not thyroid hormone is absorbed by the cells of the body and discuss some better alternatives to testing, supplementation and monitoring of whether or not a given approach is working.

How Does Thyroid Hormone Work in The Body?

Before we look at how most people are treated, it’s important to understand how thyroid hormone works in the body.

TSH is thyroid stimulating hormone. This is released by the pituitary gland to stimulate the thyroid so that more thyroid peroxidase (an enzyme) is made. This enzyme combines with iodine to make thyroid hormone, T4 and T3. About 97% is T4 and 3% is T3.

The body can’t really use T4, so it has to convert this into T3 which is the form that the cells of the body can use to do stuff. 60% of T4 is converted by cells in the liver, another 20% by cells in the gut and the remaining 20 or so % is converted by cells in the peripheral tissues of the body (muscles, fat, etc.)

Why Is Synthroid (Levothyroxine) Sold As The Answer?

Because most of the hormone that is made in the thyroid is T4, the logic is that for those with Hashimoto’s (an autoimmune disease that slowly destroys the thyroid) and hypothyroidism (low thyroid activity) giving a synthetic form of T4 such as Synthroid or Levothyroxine will replace what the body is not doing for itself.

Then, theoretically, the rest of the process will happen as it should – the liver will do it’s thing, the gut will do it’s thing, and the rest of the peripheral tissues will do what they are supposed to do.

Oh, if it were only as simple as that!

Many Things Hinder the Conversion of T4 to T3

There are many, many factors that can cause problems all along the way in getting this synthetic hormone into a form that the body can use and, getting the tissues of the body to effectively absorb it.

And for millions of people, this process just does not work. This is because there are so many things that disrupt thyroid hormone’s ability get into cells, these include: dieting, anxiety, stress, insulin resistance, obesity, diabetes, depression and bipolar disorder, high cholesterol and triglycerides, chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases (Alzheimer’s, Parkinson’s and multiple sclerosis), migraines, cardiomyopathy, and aging.

(Here’s a really interesting graph that shows how this works.)

Testing TSH, T3 and T4 Doesn’t Measure Thyroid Hormone In The Cells

What most doctors learn in medical school is that testing TSH and total T3 and total T4 will tell you how the thyroid is functioning or how well thyroid hormone replacement is working.

This is just not true. This false idea is based on assumptions about how thyroid hormone gets into the cells of the body. In the old, out dated theory, it is thought that thyroid hormone simples diffuses or is absorbed like soda from a straw into the hungry mouths of eager cells.

More recent research has shown that its not diffusion at all, but rather active transport that requires energy from the cells to get the hormone in. What this means is that anything that compromises energy production in the cells (mitochondria make energy in the cell – so things that mess with the mitochondria) will cause less thyroid hormones to get into cells.

These include all of the list of conditions mentioned above and stress is one of the most profound blockers of this process.

In addition, the different thyroid hormones require different amounts of energy to get into the cells. For example, T4 takes more energy to get into cells than T3. (This is why many people do better on T3 only supplementation or combinations of hormones that combine T3 and T4.)

So if you have any or some combination of these conditions: dieting, anxiety, stress, insulin resistance, obesity, diabetes, depression and bipolar disorder, high cholesterol and triglycerides, chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases (Alzheimer’s, Parkinson’s and multiple sclerosis), migraines, cardiomyopathy, and/or aging, and you are taking T4 only, you are going to have a very hard time getting that into the cells of your body.

Almost Everybody Has This Problem

That pretty much covers most of the population on thyroid replacement hormones.

This is important because T4 has to get into cells to be converted. What’s also interesting is that measuring serum T4 (T4 in the blood) won’t tell you anything about how much of it is getting into the cells. Instead, you have to measure Reverse T3 and free T3 levels and measure their ratio. (More on this in a moment).

This is also why some people have normal numbers but still have lots of hypothyroid symptoms (fatigue, hair loss, joint pain, brain fog, constipation, depression, low libido, etc.) even though their lab results are normal.

They have low T4 levels in their cells and more in their serum. So everything looks hunky dory, but they feel terrible. TSH testing will not pick up this problem because TSH is produced in the pituitary and this gland absorbs thyroid hormone very differently than the rest of the body.

The Pituitary Not the Thyroid Determines TSH Levels

The pituitary is much more sensitive to thyroid hormones and transports thyroid hormone differently than all other cells in the body.

In the pituitary, thyroid hormone does not depend on energy to get into the cells. The transporters for T4 and T3 in the pituitary are also not inhibited by numerous environmental toxins and substances produced by the body during physiologic stress and dieting, things  that inhibit thyroid transport into other cells in the body, including bilirubin and fatty acids.

In other words, all of the stuff that prevents the cells in the rest of the body, do not affect the absorption of T3 and T4 in the pituitary. So TSH does not reflect the hypothyroid state in the rest of the body and is really only a good measure of thyroid hormone IN THE PITUITARY.

Thyroid hormone is absorbed into the cells of the liver differently than it is by the cells of the pituitary. This is really important to understand and most doctors and endocrinologists do not know this. Since 60% of T4 is converted in the liver, this makes a huge difference.

Why Dieting Can Make Thyroid Hormone Less Available

Many overweight people with Hashimoto’s try to lose weight and are just not able to. This has lead to a huge industry of weight loss drugs, products and procedures.

But what many people do not understand is that the reason that weight loss may be so difficult for these people is that the very process of trying to lose weight may be preventing them from being able to absorb thyroid hormone into their cells.

This creates a vicious cycle of dieting, yo-yo weight loss and gain and miserable results. And all those things actually create a state of a slower, more sluggish metabolism that all but dooms them to failure.

If thyroid hormone is not being absorbed by the cells, then you have a state of cellular hypothyroidism and your body slows down and does not lose weight. And this state of poor cellular absorption of thyroid hormone is not seen in laboratory results unless free T3 and Reverse T3 levels are done.

A very interesting study published in the American Journal of Physiology-Endocrinology and Metabolism, Van der Heyden et al studied the effect of dieting on the transport of T4 and T3 into the cell.

It was found that dieting obese individuals had a 50% reduction of T4 into the cell and a 25% reduction of T3 into the cell due to less energy in their cells, showing that in such patients standard thyroid blood tests are not good indicators of thyroid hormone levels inside the cells.

This also demonstrates why it is very difficult for obese patients to lose weight; as calories are decreased,  metabolism drops.

This will, however, not be detected by standard TSH, T4 and T3 testing.  In addition, there are increased levels of free fatty acids in the blood with chronic dieting, which further suppresses T4 absorption into the cells and this causes more cellular hypothyroidism.

How You Feel Is More Important Than What Your Lab Tests Say

Another interesting study published in the Journal of Clinical Endocrinology and Metabolism, by Zulewski et al clearly shows that TSH is not a useful measure of proper thyroid replacement because there was no connection between TSH and tissue thyroid levels.

Levels of T3 and T4 were better, and T3 was the best indicator. However, a thorough assessment of how patients felt determined by how many signs and symptoms of hypothyroidism they had (i.e. weight gain, fatigue, hair loss, depression, low libido, brain fog, etc.) was shown to be the most accurate method to determine proper thyroid hormone replacement dosage.

How you feel is a lot more important than what your TSH test results say.

This Is Why You Are So Tired All The Time

What all of this means is that people with Hashimoto’s and hypothyroidism who are on T4 only thyroid replacement hormone feel tired all the time, are losing their hair, can’t lose weight, etc. and just generally feel like crap because this hormone is not getting into the cells of their body.

When thyroid hormone doesn’t get into the body’s cells, it can’t do its job.

There Is Another Way

It doesn’t have to be this way. You can change this by, first, testing appropriately to see how well your cells are absorbing thyroid hormone and then by making changes in your diet, lifestyle and medications (if necessary) to make sure that you are converting and absorbing enough thyroid hormone for it to work in your body.

The proper way to test whether of not your cells are absorbing thyroid hormone is to order free T3 (fT3) and/or T3 and reverse T3 (rT3). And then to measure their ratio: the proper ratio of free T3 to reverse T3 is greater than 20. The proper ratio of T3 to reverse T3 is greater than 10.

If your numbers demonstrate that you have high reverse T3 and a low ratio, then you are not absorbing thyroid hormone into the cells of your body.

The next step is to improve the function of the areas that convert thyroid hormone and to clean up your diet and alter your lifestyle to support proper absorption of thyroid hormone.

Since 60% of T4 is converted into T3 in the liver is vitally important to make sure that you improve liver function and make sure that your liver is working properly. A good liver detox and changes in diet can accomplish this.

The next step is to clean up your gut and make sure that you don’t have intestinal problems or inflammation of the intestines that can slow or prevent proper absorption and conversion of thyroid hormone.

Next, you need to supplement and gradually heal the body so that the many conditions that can slow or stop absorption of thyroid hormone are reversed and make sure the cells of your body have enough energy to get thyroid hormone into your cells.

Lastly, you may need to start taking T3 or try a thyroid hormone that contains both T4 and T3. This will insure that enough T3 is getting into the cells of your body.

30 Minute Confidential Telephone Consultation

I am offering a 30 minute telephone consultation if you would like to learn more and discover whether or not you have issues that may be preventing your cells from absorbing thyroid hormone.

Click on this link to schedule the consultation.

Its Not Easy, But The Results Can Be Dramatic

This is not a simple process and you need to work with someone who understands how to guide you through this process.

That’s why I have created a simple 60 day program that can dramatically improve the way the cells of your body absorb thyroid hormone:

This program includes:

* Free T3 (fT3) and reverse T3 (rT3) testing

* A 30 day liver detox program

* A 30 day gut healing program that incorporates the Hashimoto’s Diet Plan

* Supplementation and guidance to improve cellular energy production.

* Follow Up testing

Click on this link to schedule a confidential 30 minute consultation.





van der Heyden JT, Docter R, van Toor H, et al. Effects of caloric deprivation on thyroid hormone tissue uptake and generation of low-T3 syndrome. Am J Physiol Endocrinol Metab 1986;251(2):156-E163.

Zulewski H, Muller B, Exer P, et al. Estimation of tissue hypothyrodisim by a new clinical score: Evaluation of patients with various grades of hypothyroidism and controls. J Clin Endocrinol Metab 1997;82(3):771-776.

Kharrazian, Datis, DC, Why Do I Still Have Thyroid Symptoms When My Lab Tests Are Normal? 2010, Elephant Printing


About the Author Marc Ryan

Leave a Comment:

Tiffany Chapman says

This is exactly what I’ve been needing to hear. My endo does nothing except talk about my TSH levels and my Synthroid dose and it has never sat well with me. I kept asking about what else I can be doing to address the autoimmune issue and she has always told me there is nothing else i can do. I am do glad to have found your blog, it’s been so helpful.

    Marc Ryan says

    Hi Tiffany,

    Thank you for your kind words! If you like my blog, you might like my video blog. I have lots of cool videos and interviews. Also, I have put up Week 1 of my 6 week course called healing Hashimoto’s: the 5 Elements of Thyroid Health, for free!. In this course I go into depth about what is happening in your body, why and what you can do about it. Please check it out!

    Here’s a link: http://healinghashimotos.com/


Taylor says

Truly amazing!
so what exactly does FT3, RT3, FT4, RT4, T3 uptake, individually mean and show

hope says

THANKYOU!! this post on facebook couldn’t have come at a better time. I had just finished FIGHTING and WINNING the battle with my endo to test my t3 t4 and rt3. he RELUCTANTLY tested them for me. anyway, i just got back from my appt and I want you to know i had this post IN MY hands! he was very open to hearing what i had to say and he changed me from levo to armour (i hope it helps) but, it absolutely blows my mind that he wants to treat my brain fog/anxiety/depression/and extreme exhaustion with an anti-depressant…. really? anyway, he didn’t push it on me. So, he is thinking that all my numbers are normal b/c they are in “normal” range…. I have been on 125mcg levo for 3 months and following a strict AIP diet. my tsh is .09 (was 6.18) my tpoab are 461.7 (were 550) and my free t4 is 1.5 and free t3 is 3.2 and rt3 is 23. I don’t understand the “ratios” … does it look like i’m converting it in my cells? he is putting me on 1 1/2 grains armour.

and… can you tell me how much your program costs, what about just the liver detox?

Thank you again for ALL of your information that you share with us!!! I really appreciate it and i look forward to more healing!

    Marc Ryan says

    Hi Hope,

    Thank you for your kind words! I love that you had the post in your hands! 🙂 If you can give me the units of measurement for the T3 and reverse T3, I can calculate it for you and explain the ratios. It’s written on the lab results- usually something like ng/dl or ng/ml or pg/ml..something like that. That way we can see how well you are converting.

    As far as my programs are concerned, I have a few different options. What I recommend is that we have a conversation first. I offer a free 30 minute Hashimoto’s Healing Discovery session. In it you can share where you are and where you want to be, I can make some suggestions that will be helpful right away and we can discuss program options.

    You can schedule a consultation by clicking on the button on the home page.


Hope says

Thanks Marc. I’m trying to find out the units for the Rt3… If it’s ngdl like I think… Then my ratio is 13.9… I’ll get back to you 😉 thanks again!

Hope says

The unit is NG/dl. Doc says the ratios were only used for children w Graves’ disease and some HIV antiviral something. He said he’d be anxious to know if I come up w a real use for the ratio…. Do you come up w 13.9?? And does that look like I have a conversion issue? THANK YOU! I really appreciate your time!

Hope says

Sorry for all the posts…
Free t3 is 3.2 pg/nl
Free t4 is 1.5 NG/dl
Reverse t3 is 23 NG/dl
Tsh is .09
Switching from 12 mcg Levo to 1.5 grains armour


    Marc Ryan says

    Hi Hope,

    Sorry, it took me a few days to get to this. Yes, 13.9. Ideally, we’re looking for a ratio of 20 or higher with the free T3/rT3 ratio. So yes, there may be any number of issues. It could be one of conversion or it could be other things like the adrenals or iron deficiency.


Bonita Nelson says

I am a 59 yr old woman who is an insulin dependent diabetic. I also have cirrhosis of the liver,( hereditary) hypothyroidism, arthritis, IBS, diviticulosis, reflex, chronic fatigue and depression. I am being treated with Synthroid .137 mcq, 50 units levimir insulin at night, glimepirde 2 mg in the mornings, Lexapro for the depression and take lisinopril 5 mg. A little over 2 years ago, I had a stomach banding and I lost around 30 pounds. This was done over 2 years ago through Duke University. Losing weight was suppose to help with my liver issues, but it hasn’t. I have tried everything to lose weight, to get off the insulin. All the doctors I have seen concerning my thyroid keep telling me my T3 and T4 are within normal limits and dismiss it….even the doctors I have seen at Duke University. I am so tired of feeling bad and feeling like I am on a treadmill!! I have to have a knee replacement soon and with all of my medical issues, it makes healing so hard. ( had other knee replaced 8years ago)
I have yet to find a doctor that connects the dots to see that everything is tied together! Each one looks at their area of speciality and dismisses the other symptoms. Everyone wants to give you another pill, which I refuse due to my liver status.
Please, ANY help or suggestions would be greatly appreciated!

    Marc Ryan says

    Hi Bonita,

    Thanks for your comment. There is no easy answer to this because Hashimoto’s can get quite complicated very quickly. Yes, it’s incredibly common for people to have normal lab work and still feel terrible. This is because lab testing is not the be all and end all and what you feel is clinically relevant and diagnostically significant.I try to explain this to my doctor colleagues and unfortunately many have been so indoctrinated by the pharmaceutical approach that they have lost sight of this basic truth.

    The most important thing for you to understand is that this isn’t a thyroid problem. It’s an autoimmune disease and the thyroid issues make it impact many other systems of the body over time. So it becomes a multi-system problem. And underlying all of this is the destructive inflammation that is at the root of autoimmune disease. So you need to do everything you can to eliminate and reduce that inflammation. The place to start is with your diet. Get off of gluten, dairy and soy 100%. Don’t cheat ever. That alone will improve your liver and many other symptoms.

    There is much more you can do after that. I offer a free 30 minute Hashimoto’s Healing Discovery session. In it you can share your biggest health challenges, I can make some suggestions that will help right away and we can discuss how else I may be able to help. If that interests you, you can schedule by clicking on the link on my homepage.

    Best, Marc

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