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.  

Putting the Pieces Together: A Tale of Autoimmunity

The horrible thing about shows like House and ER is that they give the impression that doctors care about "solving" your case and will put in the effort to diagnose and treat the underlying problem.  My experience is that doctors treat patients based on symptoms, medical history,and lab results. That sounds reasonable at first but often those things are a snapshot of the problem.  They don't dig deeper because if they treat the symptoms and the patient stops complaining, job done right?

Currently my doctors think I don't feel well because I don't sleep well enough and I'm depressed, despite the fact that I've assured them I sleep as well as I ever have and I don't feel depressed, just annoyed at them.  I've cried 3 times in the year since my diagnosis.  Every one of those times was in frustration over not being physically capable of living a normal life.  I refuse to be emotionally castrated by anti-depressants because some doctors think I shouldn't have any negative emotions about my chronic illness.  Besides that, depression is a symptom of hypothyroidism so even if I felt depressed I wouldn't be convinced that it's the cause and not another symptom.

When I was diagnosed with Papillary Carcinoma of the Thyroid (PCT), I had virtually none of the "established" risk factors for having it.  No one in my family had a history of thyroid cancer or thyroid disorders, and I'd never had any significant exposure to radiation.  Aside from being female and roughly in the right age range, the doctors didn't know why I would have it.

After my surgery they did a full biopsy and one of the things they found was that I was in the early stages of chronic thyroiditis.  In poor countries, chronic thyroiditis is usually caused by a lack of iodine, but because of iodized table salt, most people in affluent countries have thyroiditis due to autoimmune disorders.  My doctor never mentioned this during my post-op appointment, though I had read it in the pathology report.

It wasn't until I asked to be referred to another endocrinologist that I was told there was indeed thyroid autoimmune anti-bodies in my blood, so much so that they couldn't tell if I still had cancer.  When I tried to ask her more questions about it, she refused to answer, telling me that she didn't feel it was relevant. My experience is that the first step toward getting the worst care possible is letting doctors decide for you what is relevant.  I started doing my own research.

Hashimoto's and Papillary Carcinoma of the Thyroid 

It literally took me less than 30 seconds to find a 2012 study that showed that patients with Hashimoto's Thyroiditis (HT) are 16% more likely to have PCT, and 53.6% more likely to have Stage 4 disease (distant metastases).  Finally, there was at least the beginnings of an explanation of how I ended up with cancer and suddenly I feel so much more lucky to have had my cancer caught so early, a stage 1 tumor with minimal lymphatic invasion.

According to the study, the link between the two was first theorized in 1955, so even though this is a recent study, the link has been recognized for decades.  This was one of a number of studies I printed out for my doctor for our follow up appointment.  When I started talking to her about Hashimoto's she brought up it up to me as though it would surprise me at how much better informed she is than I am, and maybe I'd realize I was a dumb patient that should just go away and do as I'm told.  I handed her my printed copy of the study.  She looked crestfallen.

In this very limited respect, she is correct that the fact that I had Hashimoto's and then got PTC is not relevant because it already happened.  If I had been diagnosed with Hashimoto's at a younger age, a lot of problems, possibly even the cancer itself, could have been prevented, but hindsight doesn't cure cancer.

That doesn't make the disease irrelevant, though, for two very big reasons.  First, I still have Hashimoto's Thyroiditis even though I don't have a thyroid. My blood stream is still teaming with auto-immune antibodies and will be for years.  This means that the consequences of having treated a person with Hashimoto's with a thyroidectomy are still relevant.  Secondly, the Hashimoto's Thyroiditis is just another stepping stone. It explains the cancer.  What explains the Hashimoto's?

Hashimoto's Thyroiditis After a Thyroidectomy

It was not surprising to me in the least to know that very little (published) research has been done about the effects of thyroid autoimmune antibodies after a thyroidectomy.  Eventually as the cause for concern (thyroglobulin protein produced by thyroid cells) is no longer present, the antibodies will decrease in numbers, though as I understand it they'll never fully disappear.  I'm sure from the doctor's perspective, it's "job done" once the thyroid is gone.

Antibodies are what your immune system makes in response to perceived microbial invader.  Anytime your body gets sick, it tries to manufacture as many of the antibodies as it can.  The antibodies are specially designed to attack and destroy a particular invader.  In autoimmune disorders, the body thinks that normal, healthy tissue is an infection and tries to attack it.  This means that my body has been pumping out large doses of thyroid antibodies for years, perhaps my whole life.  Imagine your body thinking you were sick for 33 years.

What I did find was an interesting study that showed that patients with high levels of certain thyroid autoimmune antibodies (anti-TPO) had much worse symptoms even when their thyroid hormones tested as normal (euthyroid).  The link above is just to the abstract but I was able to read the whole study using my local libary's health database. This excerpt from the study essentially describes my symptoms:

In our female study collective, we could demonstrate that the following general symptoms were associated with higher anti-TPO levels: chronic fatigue, dry hair, whether patients became easily fatigued, dysphagia, chronic irritability, and chronic nervousness.

It goes on to conclude that the symptoms could be related to high levels of anti-TPO antibodies, not just hypothyroidism, and that patients with Hashimoto's Thyroiditis have worse symptoms.  I also found a paper that concluded that patients with HT have more complications after a thyroidectomy.

I tried to discuss with my doctor whether the symptoms I'm having now might be caused by the antibodies and whether that meant they would resolve themselves as the level of antibodies decreased. Rather than having what I hoped would be a productive dialog about thyroid autoimmune disorders, she shrugged, said "Maybe," and decline to look at the study I'd printed out.

I still feel that Hashimoto's may be relevant to the question of why I still feel unwell a year after I started treatment.  Unfortunately, my doctor didn't want to talk about it at all.  I don't get the antibody levels in my lab reports but I do know they are dropping so there's a chance that in a year or two they may dip low enough and these symptoms might "magically" resolve themselves.  If that is the case, the good news is that I need to do nothing but wait.  The bad news is that I might have another year or two of feeling unwell with no symptom relief.

It's ALL Related

Even if the thyroid antibodies aren't the cause of my current misery, it's important for another reason.  In 2005, after battling with doctors for several months, I was diagnosed with endometriosis after having symptoms for 9 years.  Endometriosis is a disease where tissue similar to the lining of the uterus grows outside the uterus, causing blood filled cysts that burst and cause massive scarring, pain, and infertility.

Although endometriosis is not considered an autoimmune disorder, it is strongly associated with several other autoimmune disorders, including autoimmune thyroiditis.  In an article published in May 2013, the authors wrote that the underlying causes for both diseases might be the same. This means that the endometriosis, thyroiditis, and cancer could all be the result of a single, underlying autoimmune disorder.  When I mentioned this to my doctor her response was, "So what?"

"So what", indeed.  I'd really hoped, again, that I'd be able to talk to her about autoimmunity and what research there was about treating the root cause of both diseases, as the authors of the 2013 article suggest.  In addition to being related to each other, both endometriosis and autoimmune thyroiditis are strongly correlated to a host of other autoimmune diseases which means that I am at greater risk for many other autoimmune disorders.  If they could treat the underlying cause it might reduce or eliminate the risk of my developing other disorders like Type 1 diabetes, rheumatoid arthritis, or fibromyalgia.

The authors of both the 2002 survey and the 2013 article suggest that autoimmune disorder screening should be performed for all women with endometriosis.  If my doctors had screened me in 2005, could they have found the thyroiditis and prevented the cancer?

What Does it Mean?

To be honest, I'm not entirely sure what all of this means.  I'm incredibly disappointed by my doctor's refusal to discuss the topic of thyroid autoimmune disease.  I'm worried that without treating the underlying disease, I'll continue to have problems for the rest of my life with these various, related diseases cropping up.  I'm hoping talking to my primary doctor and perhaps getting referred to an immunologist might provide more information and testing that might ease my mind.

What I do understand, and have read in other articles, is that if you have Hashimoto's Thyroiditis and pelvic pain, you should get screened for endometriosis.  If you have Hashimoto's, regardless you should get checked regularly for Papillary Thyroid Carcinoma.  If you have endometriosis, you should get checked for both.  Hindsight won't cure me, but maybe having written this it will save someone else the same trouble.

Recovery: 8 Months in 2 Words

It's been a little more than 8 months since I lasted wrote here. The one year anniversary of my surgery came and went and I am still sick, still not "cured". With the surgery and radiation behind me it seemed that all that was left was the work of getting well again. I can sum up the last 8 months of recovery in two words: It's hard. Though I was terrified of spending the night in a hospital and prepping for radiation was exhausting, I never expected these parts of my treatment to be the hard parts about having cancer.

Procedures are scary, but they happen to you, sometimes while you're not even conscious. Recovery is scary, too, but in a soul-grinding way where you have to experience every excruciating moment of your inability to function like a normal person: Cleaning the drain every time I shower because so much hair falls out, days where I can't keep food down, days where I can't stand up or walk so I crawl on the floor instead, taking pills that make me feel weak and ill because without them I'd die, going to sleep exhausted and waking up tired.

When I started this blog, shortly after my diagnosis, there were several reasons for writing. First, for myself to have a place to put down and process everything that was happening to me. When I can write it out as story, I can see it more objectively and less painfully. Second, was to have a way to keep those who cared but were too far away informed about my treatment. The last reason is that I wanted a record of my experience for anyone else who might be about to start the same journey. This last reason is the reason that I've decided to start writing again.

After my last blog post, my recovery seemed to be going well aside from repeated infections of my salivary glands which were damaged during the radiation treatment. In February, after having spent nine months doing treatments and trying to recover from them, I finally returned to work. Every day since then has been a struggle. I feel like I do nothing but work and sleep. The weekends are spent recovering from the weekdays. I no longer go grocery shopping with any regularity. My apartment is constantly dirty. If it weren't for my boyfriend I think things would be completely unmanageable. He gives me the motivation to do as much as I can and picks up the slack when I cannot do any more.

It scares me to say, but I'm running out of energy to do the work of getting well. Spurred by that fear, I've decided to step up my involvement in my recovery. I've started putting all those anatomy and pathology college courses to work, doing my own research into my condition and the treatments. I've begun the long and difficult task of fighting with my doctors to get the individualized care I need to complete my recovery.

I learned from the period of my life where I struggled with endometriosis that doctors don't want complex patients. They want easy solutions that they can cure with lifestyle changes or pills that will just make you go away. Most doctors only see the symptoms and therefore only want to treat the symptoms. They don't want to try another surgery, an experimental treatment plan, or anything that requires them to stretch themselves. In my experience, they will treat you as poorly as you let them.

I am exhausted now and I'm scared I've put this off too long, but I am also angry at the way my life is and the attitudes of my doctors so I'm hoping that will give me the energy to complete this fight. Upcoming posts will be about my research, the treatments I'm trying, and the struggles with my doctors to get the care I need to get well. I'm hoping by sharing this here, it will benefit others who are now on the recovery side of thyroid cancer treatment. Maybe it will also help those close to me to understand. Chronic illness is hard for everyone and I often feel like they think I should be better by now. They deserve an explanation of why I am not cured, and to see how I am trying to be. The road to recovery is not a six lane, smoothly paved highway. It's a dirt track through the wilderness with few signposts. This is the hard work of recovery, and this is how I will get well again.