Failing the Thyroid Function Tests

In the year since I started cancer treatments I've had a lot of time to think about all the events leading up to my cancer diagnosis.  I felt completely dejected about having to leave the diagnostic ultrasound program without completing my degree.  Instead of a job skill I got cancer and thousands of dollars in student loan debt.

The more I dig into what is going on with me, the more grateful I am for those nine months of my life. Most especially I am thankful for my time spent with Dr. Peck, my pathology professor.  From the very first lecture, I knew she would be one of my favorite instructors.  Though she is a tiny woman, she is tough as nails with a larger than life personality and a heavy Russian accent.  The first thing she said to us after introducing herself was: "You may have noticed I have an accent. You will get used to this."

In her class I learned so many important things about the diagnosis of disease.  She taught me that hardly any patient ever has the "classical" presentation (signs/symptoms) of a disease, that "what's most common is most common", and most importantly that "tissue is the issue."  Except in a rare few cases, neither blood tests nor medical imaging are considered definitive for a diagnosis.  You must look at the tissue itself to know if the disease really exists.

For the last year, every six weeks I have been going to have my blood drawn for thyroid functions tests. The tests are intended to test thyroid function, but I don't have a thyroid anymore. As I have continued to feel unwell I started to question what these tests were really testing.

Thyroid function tests don't directly test the function of the thyroid.  What the test are a few hormones which might indirectly indicate whether there is a problem if their levels are abnormal.  An important thing to note, is that all of theses are serum tests, meaning they are testing what is in the blood and not what is in the tissue.  It's not possible to test at the tissue level without doing a biopsy. This fact will becoming important shortly.

Thyroid Stimulating Hormone (TSH) Testing

Let's start with TSH testing.  TSH is a hormone produced by the pituitary gland, sometimes called the "master gland", in response to low thyroid hormone in the circulatory system. .  It is the only gland in the body that has a direct connection to the brain.  Hormones released by the pituitary gland tell other glands to release their own hormones.  With respect to the thyroid, as TSH increases, it tells the thyroid to produce its hormones.  As those hormones rise, it tells the pituitary gland to stop producing TSH. This method of regulating hormones is called a "feedback loop" and it's how most hormones are regulated in the body.

That's how it works in a normal thyroid.  Without a thyroid, there is no feedback loop. My body doesn't make its own thyroid hormone so the TSH doesn't affect how much thyroid hormone is in my system.  TSH is produced in response to the amount of serum thyroid hormones.  

In other words, measuring TSH measures whether my brain thinks there's enough synthetic hormone in the system.  In terms of telling whether I feel well, it's a completely meaningless measurement.  The reason they measure TSH in patients with no thyroid who have had cancer is because TSH can also stimulate thyroid cancer cell growth so the theory is that if the TSH is low enough, cancer growth will be suppressed, and the cancer will be less likely to recur.  Unfortunately, studies have shown this might not be the case.

Thyroxine (T4) Testing

T4 is one of the hormones produced by the thyroid and is the "transport" form of the thyroid hormone.  Free indicates that it's only what is in the blood, not in any tissues or bound to any proteins. In patients with a thyroid, testing T4 can tell whether the patient is producing too little (hypothyroid) or too much (hyperthyroid) thyroxine hormone.  Comparing TSH and T4 levels is an established way of determining both whether there is a problem related to thyroid hormones and whether the problem is in the thyroid itself (primary) or caused by a dysfunction of the pituitary gland (secondary).

When you don't have a thyroid, you don't make T4.  This means that what T4 testing says is that I'm taking my pill every day.  I could tell you that without a blood test.  To some degree, it's important to measure because it keeps the doctor from making gross errors in medication amounts which can be damaging, but because this is just measuring the transport form of the hormone and only the levels in the blood, it doesn't say whether the tissue is responding well to the synthetic hormone treatment.

Triiodothyronine (T3) Testing

T3 is the working form of T4.  The thyroid produces a small amount of T3, but for the most part T3 is made at the cellular level in each organ by converting T4 to T3.  This allows each organ to convert the amount of T3 they need, independently of other organs.  "Free" indicates that it is what is free floating in the blood.  Only a very small amount of T3 is "free".  Most of it is bound to proteins, essentially disabling it from use.  Total T3 is a test of both the "free" and "bound" T3 together.  

T3 testing isn't regularly done because the test is considered unreliable.  While T4 can be in the system for a week, T3 will dissipate in about a day, making the levels of T3 highly variable even in a 24-hour period.  On top of that, most of the T3 that can be found in the blood is bound up to proteins so only a very small fraction of the already small fraction is available to cells anyway.  Most T3 is made at the cellular level so what is in the blood doesn't really say anything about what's in the tissue.

It's possible to get some useful data about T3 serum levels but only if the test is very controlled and performed days apart instead of weeks apart as is done for TSH and T4 testing.  In other words, for the practical purpose of balancing patients without a thyroid, there isn't a way to use this test reliably.

What's "Normal" Anyway?

If you've ever had any blood tests done you might have noticed on your results something called a reference range.  This is a range of samplings from people thought to be "normal" and in most cases the reference ranges are huge.  This means that the average range across many people is very large, but it doesn't mean that the average range of normal for an individual is the same size as the reference range.

In fact, it's usually the opposite.  Your personal reference range will be a small portion of the lab's reference range.  The range at which you will feel "normal" will be much smaller, but doctor's tend to disregard this and tell you that your labs are normal even when you could have subclinical hyper- or hypothyroidism.

A 2012 study published in the European Journal of Endocrinology discusses the difficulty of balancing thyroid hormones based on reference ranges:

Some studies showed that hypothyroid patients treated with L-T4 had impaired well-being despite their normal TSH levels. Meanwhile, patients with moderately suppressed TSH levels postoperatively had higher serum FT4 levels and unchanged serum FT3 levels compared with their native levels...

In other words, these patients had to be given more than normal amounts of synthetic T4 to achieve normal levels of TSH and even though there was more T4, the amount of T3 didn't go up along with it, and on top of all that they still had not managed to make the patient feel normal.

Many doctor's exclusively look at TSH to determine whether the patient's dosage of T4 is correct, but the study goes on to question whether we really understand what should be normal for patients without a thyroid.  With T4 alone it is seemingly impossible to balance thyroid hormone values in the blood serum.

Tissue is the Issue

As I mentioned before, all the above tests look at the hormones in my blood and none of them measure whether the thyroid replacement therapy is working, where "working" means adequately replacing the function of my missing thyroid.  Testing at the tissue level on a live human subject is not a great idea because you're talking about taking out pieces of brain, bone, or muscle.  Remember, T3 is largely created at the cellular level and each organ needs a different amount of T3 for proper functioning.  This fact alone means that no blood test will properly reflect what is going on on an individual organ level.

In 1995, a group of researchers set out to find what was really going on by doing research on the scientists' mascot: the lab rat. Their research studied the effects of varying doses of T4 on the brain, heart, lungs, kidney, liver, spleen, and muscle.  What the study found was that the effects on T4 on tissue T3 levels varied and there wasn't one dose that would make every tissue operate normally.  Replacing T4 doesn't replace the normal function of the thyroid.

A Big Fat Fail

In the end, what thyroid function tests can tell about a patient with no thyroid is very limited.  They do not directly test the effects of hormone replacement at the tissue level.  The range of normal values isn't useful under normal circumstances unless something is seriously wrong and may not even be correct for patients without a thyroid.

For the past 6 months I've suffered from debilitating muscle fatigue and pain even though all my lab values have been "normal".  I wake up every day tired and I go to sleep exhausted.  I can't remember what being rested feels like and yet my doctor insists that I'm "normal".  It almost feels as though she's saying "If you just believed what the test says you would feel perfectly fine."

Thyroid function tests are not definitive and should not be treated as such.  Looking at TSH and adjusting medication based off of the one number that means absolutely nothing in terms of the effectiveness of the treatment is so blatantly wrong that it surprises me that this is the measure most doctors use.  Most importantly, reading these research papers I have discovered the biggest flaw with these tests: None of them consider quality of life for the patient.  It doesn't matter if the lab values are spot on if the patient feels like crap every day.