2014 ATA thyroid therapy guidelines: 1. Levothyroxine

American Thyroid Association-LevoIn this series of posts, I paraphrase a 2014 thyroid therapy guidelines document in a way that even the brain-fogged hypothyroid patient can understand more quickly and easily than reading the original version.

MY SUMMARY’S AIMS AND METHODS

Every thyroid patient understand the basics about what is being said about their therapy by the American Thyroid Association (ATA).

These people’s guidelines are cited in other guidelines all over the world today. They have high status among endocrinologists, so they seem to be the ones who ultimately write the rules that overrule our well being.

I’ve decided to use everyday question and answer format, and I’ve written their answers using “we” as if they, the guideline writers, are speaking to you directly.  I’m attempting to translate their reasoning into conversational discourse. Anything outside of “quotation marks” is my paraphrase and includes my interpretations of their attitude toward the subjects they cover.

If you doubt my paraphrases are fair, go to the original article and read the section number. You can decide whether I have misinterpreted their attitude and/or their stance.

Wherever I’ve interpreted, I’ve used my broad reading in thyroid journals including ATA’s main journal called “Thyroid,” my understanding of other guideline documents written by the ATA (such as the 2012 guidelines by the ATA and AACE) and other articles written by some of those who served on this ATA committee.

Overall, notice the order and priority of questions. I’m giving the summary in the order they present it.  The questions they start with are not about goals of all thyroid therapy, but rather about the correct use and defense of “levothyroxine” alone.

PARAPHRASE BEGINS

Q: Who wrote these guidelines, how, and why?

A: In 2014, the American Thyroid Association gathered a task force on thyroid hormone replacement because of concerns that some patients “feel unwell while taking levothyroxine monotherapy.” We eleven co-authors went through a process of identifying 24 questions, reviewing literature, consulting a bioethicist, following processes that were supposed to be designed to minimize bias. We even gained “stakeholder input” at a national meeting.  In the end, we achieved consensus on all points.

Q1a. Do we think levothyroxine monotherapy should be the standard of care for all primary hypothyroidism?

A: Yes, because the body metabolizes T4 hormone, because it resolves the symptoms of hypothyroidism, has long term benefits, few side effects, is easy to take, can be absorbed easily, has a long half-life in the body, and it’s cheap.

Q1b. What are our goals for levothyroxine replacement in primary hypothyroidism?

A: Our goals are: 1. To resolve all hypothyroid symptoms and signs, 2. to normalize TSH and improve T3 and T4 concentrations, and 3. to avoid overdose (thyrotoxicosis) especially in the elderly.

We have tied together these goals so tightly that no symptoms and signs of hypothyroidism can possibly exist while goal #2 is being achieved. Goal 2 is way more about normalizing TSH and supplying T4 than about optimizing your T3, and goal #3 is primarily about preventing TSH from being suppressed. TSH must not be suppressed because of statistical risk association studies (which have largely ignored the full range of T3 levels in those whose TSH has been suppressed by levothyroxine therapy).

Q1c-d Are other hypothyroid symptoms and signs beyond TSH, T3 and T4 tests relevant to the effectiveness and dosing of levothyroxine?

A: No. Because these symptoms can be caused by other health factors, we declare that they probably are.  We have not cared enough to do studies on your symptoms because we believe all valid symptoms have to point to a non-normalized TSH or an insufficient T4 dose or else they are not really thyroid hormone symptoms.

Q2 Which levothyroxine product is better than the other?

A: We want you to stay loyal to brand names of levothyroxine. Don’t be lured to generic alternatives that are declared to be bioequivalent. Don’t switch between brands because it can change your thyroid hormone levels. It really does not matter if you take this medicine as a tablet or a gel capsule.

Q3 How can you improve levothyroxine absorption and metabolism?

A: To be well on levothyroxine, you have to be aware of many factors that limit levothyroxine effectiveness. Your symptoms may be a result of your own failure to absorb this medication properly and/or metabolize it to enough T3 hormone.

For example, you must take your levothyroxine 60 minutes before breakfast or at least 3 hours after your last meal of the day, and at least 4 hours away from calcium and iron. Certain GI conditions like gastritis and celiac disease will interfere.

In addition, ineffectiveness of this medication may be blamed on a wide variety of supplements and medications, like estrogen and stomach-acid-lowering medications, that can interfere with either its absorption or its metabolism to the active hormone T3.

Q4 How do we adjust your levothyroxine dosage?

A: By TSH alone, of course. Low TSH always means too much levothyroxine and high TSH always means too little.

We consider various factors when we estimate the dose you’ll need to normalize your TSH, such as your weight, your age, pregnancy, thyroid gland status, and presence of heart disease. If any of these factors change, we simply test your TSH again and adjust your dose as needed to normalize your TSH.

Q5 What can we do if levothyroxine interferes with other health conditions?

A: If you’re allergic, use a different L-T4 brand. If your iron is low, raise it.  If you have a cardiac condition, you may need to suffer on a lower dose or take beta-blockers with your levothyroxine. If you have mental health problems while your TSH is normal, get treated separately for that, because that’s a separate medical condition. 

Q6 How do we manage your levothyroxine if you are old, pregnant, or don’t take your meds properly?

A: If you are older, you will get lower doses to start with. Even though we will still test your TSH, we believe you’re going to be just fine if your TSH is above range because it’s so common in untreated old people to have a higher TSH.

If you’re pregnant, to protect your fetus, we’ll keep your TSH to trimester-specific reference ranges, we test you as frequently as every month, and we may ask you to take a double dose once a week.

If you are an infant born hypothyroid, we will maintain your T4 in the upper half of reference and your TSH in the lower half of reference and we test you every 1-2 months for the first year.

During your life, if your TSH is elevated because we suspect you are forgetting to take your doses, we will protect you by making you take one big dose once a week.

Q7a-c What do we think of your T3 hormone levels while on levothyroxine?

A: We have no recommendation to make on any of these three questions related to T3, just summary statements and a discussion of some literature.

Overall, we haven’t done enough research to say whether a certain T3 level anywhere within or even below reference is bad for you. It’s a biological fact that everyone converts T4 to T3, and the TSH proves that your pituitary gland is getting enough T3. If you have hypothyroid symptoms, your TSH will be high. Therefore, we haven’t worried enough about this issue of T3 levels to study the relationship between your T3 levels and your symptoms or overall health.

We think that dosing T3 is not good for you because it makes your T3 levels fluctuate more than they would in a normal person.

We don’t trust the T3 and Free T3 immunoassay tests we’ve developed. We know they are not reliable at the lower end of the reference range, so we are justified in dismissing them. We’re not interested in developing or refining the testing technology further because the TSH test measures pituitary T3 and that’s good enough for us. In the future, we may choose to use the much more expensive yet accurate LC/MS/MS technique for testing in rare circumstances and research.

If your T3 is at the bottom of reference or lower and your TSH is normal, you are probably just sick, or you’re just old, or you’re taking a medicine that depressed your T3 levels, so basically you can’t blame the levothyroxine or its dosage on your lower T3.

We know that having a high T4 level can cause you to lose conversion of T4 to T3, and we know that levothyroxine causes a high T4:T3 ratio in blood. However, we simply haven’t bothered to study the harms of this T4/T3 imbalance very carefully given that your T4 is in reference range, and we haven’t noticed any significant health problems with this imbalance as long as your TSH is normal (because, as mentioned above, a normal TSH by definition means your health problems are not thyroid hormone related).

We and levothyroxine can’t be held responsible for the way certain organs or tissues might become T3-deficient.  We know that your body will have different T3 levels in every organ, but that’s up to the organ or tissue to decide in its wisdom. You might have a genetic condition like resistance to thyroid hormone in some tissues, but we’re not going to test you for that. We’d much rather have many parts of your body suffer a T3 deficit than have any single part of it, especially the heart, have too much T3.

Q7d If you are obese, depressed, have high cholesterol, or have no thyroid, do we help you achieve a higher T3 level or lower TSH level?

A: Absolutely not. People who have no thyroid are no different from people who have partial thyroid function, and any normal TSH is good for every thyroid patient.

Even if it is theoretically possible that your symptoms and health conditions could be fixed with a higher T3 level in range, this would come at the cost of raising your T4 and even worse, lowering your TSH, which we would never do. Essentially, you do not have the right to attain a T3 level that is higher in reference range if your levothyroxine dose would then endanger your health.

So sorry, higher T3 levels within range are simply going to be unachievable or not permissible for you, but that’s no big deal because we’ve fixed your TSH.

We’ve played around with tweaking some people’s T3 levels with T4 therapy and even by adding tiny doses of T3, but we haven’t had much success in helping them with these factors, on average. Therefore, we’ve largely given up on the idea that raising T3 levels makes a difference for the vast majority of our patients. We believe that some rare patients might benefit from combination T4-T3 therapy, but we’re really having a hard time identifying the few people who might benefit from the tiny doses of T3 we are willing to give them.

American Thyroid Association-FeelHypo

Q8. What are the goals for levothyroxine therapy in people with secondary hypothyroidism?

A: If you are one of the 1:100,000 people who has central, pituitary or hypothalamic disorders that cause low TSH, in that case we will have to ignore your TSH because it won’t behave normally. We will dose you to your levothyroxine so that your FT4 is in the upper half of reference range.

We really don’t care how low your FT3 levels go. However, we will make absolutely sure your FT3 is never above reference range, which happened in one T4-T3 therapy trial in secondary hypo folks. (We had to put a stop to that, even though the therapy was more successful in every other way than elevated FT3.) So, no combination therapy for you.

We don’t care what your “clinical parameters” (symptoms) are. Since it can’t be about your TSH, it’s all about your T4.

We’re not against having your doctor monitor “tissue markers of thyroid hormone action,” but your T3 and T4 levels will always trump them.  We simply haven’t bothered to study whether other biochemical markers of thyroid hormone sufficiency could help us adjust your dose.

Q9. What do you think of patients who are unsatisfied or still have unresolved symptoms on levothyroxine?

A: We will have to wait until a group of experts have developed a special clinical instrument or questionnaire that will measure your symptoms in a valid way.

We already like some tests and instruments more than others. But no matter what the results are of these surveys of symptoms and quality of life, we will always judge these results by looking at “more sensitive” and “hypothyroidism-specific tools” — namely, the TSH. By definition, this sensitive and specific tool is necessary to validate or invalidate the symptoms measured by a questionnaire.

In general, we know a “minority” of patients with normal TSH will perceive unclear symptoms that can’t be traced to thyroid hormone levels in any way because of their TSH. If you are in this minority, we will listen and acknowledge your symptoms. Then we will diligently search for other medical causes than your thyroid hormones. We already know that increasing your L-T4 dose does not always help you.

Future research will tell us whether specific subgroups might benefit from combination T4-T3 therapy, but we won’t give you T3 just because you are suffering symptoms with a normal TSH. Outside of the context of a controlled clinical trial, we can’t really tell if giving T3 will really help you, because patients’ increased satisfaction on T3 could just be a placebo effect.

Q10a-d. Would we ever give levothyroxine to a person who has hypothyroid symptoms but has a normal TSH?

A: Of course not.  If your TSH is already normal, you are euthyroid regardless of symptoms, by our definition. You don’t need levothyroxine to normalize your thyroid hormones because a normal TSH means your thyroid hormones are fine. Even if you have many hypothyroid symptoms, are depressed, or are obese, or have hives (chronic urticaria), levothyroxine can’t help you because your TSH is already normal. 

Symptoms are confusing to us because they don’t seem to correlate with TSH. There are too many symptoms of hypothyroidism that overlap between people with high TSH and normal TSH, so therefore they can’t be hypothyroid symptoms.

In general, depression in overt hypothyroid patients (untreated people with high TSH) is usually resolved with levothyroxine (normalized TSH). But even after successful therapy, there might still be a small connection between hypothyroidism and depression, since there is a slightly higher TSH on average in depressed people being treated with levothyroxine, but it was a difference between 1.9 and 1.5 on average, and that’s insignificant. Among our treated patients, an underlying depression may be caused by thyroid disease and it might become “unmasked” by treatment. A thyroid patient’s sadness might just be caused by the difficulty of accepting that they have a lifelong chronic disease.

The successes that clinical trials have seen in treating depression in euthyroid people with either overdoses of T4 or larger doses of T3 hormone like 37.5 mcg are likely no better than placebo because the trials weren’t designed to control for placebo effect. If we put a person with normal TSH on levothyroxine, we not only risk overdosing you on thyroid hormone, but we also risk deflecting medical attention away from your non-thyroidal health problems, including any imaginary “somatization disorders” by which you can make yourself feel sick.

As for hives, about 25% of people with chronic urticaria have autoimmune thyroid disease, so it could be connected to the fact that your thyroid gland is dying but not dead enough yet to raise your TSH. But levothyroxine can’t remove the hives, and our job is limited to dosing levothyroxine.

Q10e What will we do if we discover you’ve overdosed your meds?

A: If your lab test results make us suspect mistaken or intentional overdosing on any form of thyroid hormone (including some unregulated supplements sold in the US that contain thyroid gland extracts), we will stop your medication completely. We will then either re-educate you or refer you to a psychiatrist, as the situation requires.

We call this “factitious thyrotoxicosis.” If it isn’t a pharmacy error or unintentional mistake, it is a psychiatric disorder. A serious mental problem might lead you to think that ingesting more thyroid hormone will help you. You might have a neurosis or poor body image because of your weight gain. You may be driven by “Munchausen’s syndrome,” a condition that makes you intentionally produce signs of illness.

[To be continued]

REFERENCE

Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., … Sawka, A. M. (2014). Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid, 24(12), 1670–1751. https://doi.org/10.1089/thy.2014.0028

 

One thought on “2014 ATA thyroid therapy guidelines: 1. Levothyroxine

  1. Pingback: Individual thyroid ranges are 38-68% the size of the lab reference range – Thyroid Patients Canada

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