3 steps to choosing the right thyroid hormone

August 28, 2010 in Thyroid Disorders | 18 comments

3stepsI often get comments and emails from people asking me which thyroid hormone I think is best. My answer is always the same: “It depends.” As much as some practitioners would like to make us believe, there is simply no “one size fits all” approach to thyroid hormone replacement.

Statements like “Synthroid is best” or “I prefer to use synthetic T4 with my patients” or “I only use bio-identical hormones” demonstrate a lack of understanding of thyroid pathology. Why? Because, as I’ve explained in this series, the underlying causes of thyroid dysfunction are diverse.

Giving all patients the same thyroid medication without understanding the mechanisms involved is analogous to not checking a patient’s blood type before doing a transfusion. Granted, the consequences may not be as severe, but the underlying principle is the same.

Before we continue, let me remind you that I’m not a doctor and I’m not offering you medical advice. My intent is to educate you about the various considerations that should be made when choosing a thyroid medication, so you can discuss them with your doctor. Understood? Great. Let’s move on.

Choosing the right thyroid medication requires answering the following three questions:

  1. What’s the mechanism that led to the need for medication in the first place?
  2. Are there any mechanisms that may interfere with the actions of the medication?
  3. Does the patient have sensitivities to the fillers used in the medications?

Let’s look at each of these in turn.

What’s the mechanism that led to the need for medication in the first place?

If you’ve been following this series, you know that there’s no single cause for low thyroid function. Do you have an autoimmune disease (Hashimoto’s) causing destruction of your thyroid gland? Do you have high levels of estrogen causing an increase in thyroid binding proteins and a decrease in free thyroid hormone? Do you have a systemic inflammatory condition affecting your ability to convert T4 to T3, or decreasing the sensitivity of the cells in your body to thyroid hormone?

In order to choose the right hormone, you have to know what the underlying mechanism causing the dysfunction is. Let’s look at an example.

Say you have a problem converting T4 to T3. In this situation, your TSH may or may not be slightly elevated, but let’s say it is, and your doctor prescribes Synthroid. Synthroid is a synthetic T4 hormone. Will this help you?

No. It won’t help because your problem in this example isn’t a lack of T4, it’s an inability to convert T4 to the active T3 form. You could take T4 all day long, and it won’t do a thing unless your body can convert it.

The first step in this case would be to address the causes of the conversion problem (i.e. inflammation), in the hopes that you may not need replacement hormone. If that doesn’t work, though, what you’d need in this situation is either a so-called bio-identical hormone that has a combination of T4 and T3, or a synthetic T3 hormone (like Cytomel). These will deliver the T3 you need directly, bypassing the conversion problem.

Are there any mechanisms that may interfere with the actions of the medication?

The vast majority of long-term hypothyroid patients that haven’t been properly managed find that they constantly need to increase the dose of their medication, or switch to new medications, to get the same effect.

There are several reasons for this. First, inflammation (which is characteristic of all autoimmune diseases, and Hashimoto’s is no exception) causes a decrease in thyroid receptor site sensitivity. This means that even though you may be taking a substantial dose of replacement hormone, your cells aren’t able to utilize it properly.

Second, elevations in either testosterone or estrogen (extremely common in hypothyroid patients) affect the levels of circulating free thyroid hormone. For example, high levels of estrogen will increase levels of thyroid binding protein. Thyroid hormone is inactive as long as it’s bound to this protein. If you take thyroid replacement, but you have too much binding protein, there won’t be enough of the active form to produce the desired effect.

Third, there are several medications that alter the absorption or activity of T4. These include commonly prescribed drugs like antibiotics & antifungals (i.e. sulfonamides, rifampin, keoconazole), anti-diabetics (Orinase, Diabinese), diuretics (Lasix), stimulants (amphetamines), cholesterol lowering medications (Colestid, Atromid, LoCholest, Questran, etc.), anti-arrhythmia medications (Cordarone, Inderal, Propanolol, Regitine, etc.), hormone replacement (Premarin, anabolic steroids, growth hormone, etc.), pain medication (morphine, Kadian, MS Contin, etc.), antacids (aluminum hydroxides like Mylanta, etc.) and psychoactive medications (Lithium, Thorazine, etc.).

All of these factors must be considered if a particular medication isn’t having the desired effect.

Does the patient have sensitivities to the fillers used in the medications?

Another important consideration in choosing the right hormone is the fillers contained in each medication. Many popular thyroid medications contain common allergens such as cornstarch, lactose and even gluten. As I explained in a previous post, most hypothyroid patients have sensitivities to gluten, and many of them also react to corn and dairy (which contains lactose).

Synthroid, which is one of the most popular medications prescribed for hypothyroidism, has both cornstarch and lactose as a filler. Cytomel, which is a popular synthetic T3 hormone, has modified food starch – which contains gluten – as a filler.

Even the natural porcine products like Armour suffer from issues with fillers. In 2008, the manufacturers of Armour reformulated the product, reducing the amount of dextrose & increasing the amount of methylcellulose in the filler. This may explain the explosion of reports by patients on internet forums and in doctor’s offices that the new form of Armour was either “miraculous” or “horrible”. Those that had sensitivities to dextrose were reacting less to the new form, and experiencing better results, while those that had sensitivities to methylcellulose were reacting more, and experiencing worse results.

The best choice in these situations is to ask your doctor to have a compounding pharmacy fill the prescription using fillers you aren’t sensitive to. Unfortunately, insurance companies sometimes refuse to cover this.

Other considerations

Another common question that is hotly debated is whether bio-identical or synthetic hormones are best. Once again, the answer is: “It depends.” In general I think bio-identical hormones are the best choice. A frequently perpetuated myth (in Synthroid marketing, for example) is that the dosages and ratio of T4:T3 in Armour aren’t consistent. Studies have shown this to be false. Armour contains a consistent dose of 38 mcg T4 and 9 mcg T3 in a ratio of 4.22:1.

However, in some cases patients do feel better with synthetic hormones. One reason for this is that a small subset of people with Hashimoto’s produce antibodies not only to their thyroid tissue (TPO and TG), but also to their own thyroid hormones (T4 and T3). These patients do worse with bio-identical sources because they increased the source of the autoimmune attack.

Another issue is the use of T3 hormones. As we’ve discussed, T3 is the active form and has the greatest metabolic effects. The flip side of this, however, is that it’s far easier to “overdose” on T3 than on T4. Patients with trouble converting T4 to T3 do well on synthetic T3 or bio-identical combination T4:T3 products. But for many patients with Hashimoto’s, which is can present with alternating hypo- and hyperthyroid symptoms, T3 can push them over the edge. They are generally better off with T4 based drugs.

As you can see, the best thyroid hormone for each patient can only be determined by a full thyroid work-up and exam, followed by trial and error of different types of replacement medications. Such a work-up would include not just an isolated TSH test, but also a more complete thyroid panel (including antibodies), other important blood markers (glucose, lipids, CBC with diff, urinary DPD, etc.) and possibly a hormone panel. A history must be taken with particular attention paid to the patient’s subjective response to replacement hormones they may have tried in the past.

Unfortunately, this rarely happens in the conventional model, where the standard of care is to test only for TSH. If it’s elevated, the patient will get whatever hormone that particular practitioner is fond of using without any further investigation. And all too often, as many of you can attest, this simplified and incomplete approach is doomed to failure.


Claudia August 30, 2010 at 3:39 am

Read the comments to one of your previous posts where you mentioned panax ginseng treatment for adrenal fatigue. That sounded interesting, but I have already been recommended to take hydrocortisone tablets for those problems. How do these two substances work toghether, is it possible to combine them?

Chris Kresser August 30, 2010 at 7:42 am

I don’t recommend people take hydrocortisone in general. It’s preferable to take natural compound like licorice extract to boost endogenous cortisol production than to take cortisol directly.

Jackie Patti April 16, 2011 at 11:23 am

Licorice has more of a mineralcorticoid effect than a corticosteroid effect, so should not be taken by those with high bp.

Also, whether it’s effective is going to depend non how low cortisol someone is. For example, if you have high cortisol in the morning, and low at noon, licorice in the morning is very effective as it extends the life of cortisol in your body.

However, if your body flatout can’t make enough cortisol, you need hydrocortisone (or another steroid, though I think HC is best as it can be dosed in a diurnal pattern).

Really, you can’t determine the best treatment for someone without a 4x diurnal saliva test to see the specific pattern of dysfunction.

For example, many folks who are low all day wind up high at night with insomnia. This is because the pit keeps putting out ACTH in response to the low all day and the adrenals can’t keep up, but they can produce enough to go over range at night. So… a person with this pattern may need doses of HC at 7AM, 11AM and 3PM but then need PS at night to lover cortisol to allow sleep. (Though usually when on enough HC during the day, the sleep problems will dissipate).

Lots of info here: http://adrenalsweb.org

Chris Curley August 30, 2010 at 7:29 am

Wow Chris,

a truly penetrating look into an issue that proves so frustrating for so many patients AND M.D.s   Thyroid disease is rampant,  thyroid misdiagnosis is rampant, and thyroid mis managment is rampant. 

As illustrated in your article there is a reason for all this……it is a very complex issue that needs careful testing, managment and observation. 

I am going to bookmark this and send it to many patients.

Thank You

Mario August 30, 2010 at 9:07 am

Something to think about before taking the conventional way (synthetic T4):
Hypothyroid persons using conventional treatment (synthetic T4) usually have higher levels of free T4 and lower levels of free T3 than normal persons (see Pubmed 20693806 for a comparation in pregnant women).
Hypothyroids taking thyroid medications progressed more rapidly to a diagnose of Alzheimer’s than hypo not taking thyroid medications (Pubmed 19666883).
Higher total and free T4 levels are associated with increased risk of dementia and Alzheimer’s (Pubmed 17870208, 17136019, 17132968, 16636121).

Marta August 30, 2010 at 11:47 am

Check out this article on thyroid replacement therapy:

Stabby August 30, 2010 at 5:46 pm

Spectacular stuff. It’s amazing what kind of disorders improve with good nutrition, good eicosanoid balance, gut flora, and eliminating stuff like wheat. I’ll share this series like I do all your other ones.

Alisa September 6, 2010 at 8:08 pm

Thanks so much, this sheds a lot of light on some things for me. I tried bioidentical thyroid medication for over a year, and it did nothing to help my thyroid symptoms. So I went back onto synthetics (both T3 and T4) and saw an immediate improvement. My doctor prefers the bioidentical, but said to use what works. He wasn’t really sure why synthetics worked better for me. This is the first time I have read anything that gives a clue to why!

Debbie September 23, 2010 at 5:50 pm

Your comment:  I don’t recommend people take hydrocortisone in general. It’s preferable to take natural compound like licorice extract to boost endogenous cortisol production than to take cortisol directly.
I had several tests that determined I have secondary adrenal insufficiency and am currently on 35mg Cortef since my body doesn’t produce enough. Are you saying that licorice would still be preferred to supplemental hydrocortisone?
Really great post (and blog).  Thanks!

Saponaria November 6, 2010 at 5:50 pm

Do you think products like Dr Ron’s desiccated thyroid are at all helpful? https://www.drrons.com/thyroid-adrenal-liver-pancreas-glandulars.htm

Chris Kresser November 6, 2010 at 6:16 pm

They can be, but to get the most benefit the underlying mechanisms have to be addressed.

Debbie November 6, 2010 at 6:18 pm

I’m hoping you answer my question from 9/23, but in the meantime I’ve dropped down to 25 mg. Cortef and 1 or 2 Isocort pellets before bedtime.

Chris Kresser November 6, 2010 at 6:25 pm


Yes, if you can achieve the results you want with licorice or other natural adrenal tonics that would be best. As I’m sure you’re aware, corticosteroids have adverse effects on the immune system, bone health, weight regulation and cardiovascular function – among other things. Taking them over the long-term should be avoided if possible.

Debbie November 9, 2010 at 4:36 am

Thanks Chris,

It’s the licorice root that is NOT de-glycyrrhizinated, correct?

Mike January 18, 2011 at 8:17 am

Actually Cytomel is gluten free. Who told you there was gluten in it?

Anonymous April 1, 2011 at 4:42 am

Where can I find out the gluten free status of cytomel?Thanks.

Jackie Patti April 16, 2011 at 11:30 am

T3-only is also best for those with reverse T3 issues because as long as there’s T4 available, the body will continue to convert T4 -> rT3 and the person will never get better. Doesn’t matter if it’s natural, unnatural, or your own T4, when your body gets into the “mode” of making rT3, it ekeps doing it.

I do not have Hashi’s and as far as I know have a perfectly normal thyroid gland. However, due to diabetes and adrenal insufficiency, I wound up literally bedridden with severely elevated rT3. Hydrocortisone fixed up the AI, and very large doses of T3 (enough to suppress both TSH and FT4 entirely) cleared the rT3.

I now maintain on a very low dose of T3, just enough to keep the rT3 at bay and have “normal” bloodwork.

Anonymous April 22, 2011 at 12:10 am

This is a very helpful article. I wondered if you could answer the question about Cytomel being or not being gluten-free. I have a letter from the manufacturer (to me) stating that it is gluten-free. If there is any evidence that it is not, I should not be taking it as I have Celiac Disease.

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