Wondering about the “how” rather than the “why” of autoimmune conditions

I’ve been thinking a lot about stigma, per a previous post of mine, and how I generally react to, learn about, and figure out how to deal with new chronic diseases.

I’ve observed a pattern in my experiences. When I suspect an issue, I begin with research. I read medical literature to find out the basics of what is known. I read a high volume of material, over a range of years, to see what is known and the general “ground truth” about what has stayed consistent over the years and where things might have changed. This is true for looking into causal mechanisms as well as diagnosis and then more importantly to me, management/treatment.

A lot of times with autoimmune related diseases…the causal mechanism is unknown. There are correlations, there are known risk factors, but there’s not always a clear answer of why things happen.

I realize that I am lucky that my first “thing” (type 1 diabetes) was known to be an autoimmune condition, and that probably has framed my response to celiac disease (6 years later); exocrine pancreatic insufficiency (19+ years after diabetes); and now Graves’ disease (19+ years after diabetes). Why do I think that is lucky? Because when I’m diagnosed with an autoimmune condition, it’s not a surprise that it IS an autoimmune condition. When you have a nicely overactive immune system, it interferes with how your body is managing things. In type 1 diabetes, it eventually makes it so the beta cells in your pancreas no longer produce insulin. In celiac, it makes it so the body has an immune reaction to gluten, and the villi in your small intestine freak out at the microscopic, crumb-level presence of gluten (and if you keep eating gluten, can cause all sorts of damage). In exocrine pancreatic insufficiency, there is possibly either atrophy as a result of the pancreas not producing insulin or other immune-related responses – or similar theories related to EPI and celiac in terms of immune responses. It’s not clear ‘why’ or which mechanism (celiac, T1D, or autoimmune in general) caused my EPI, and not knowing that doesn’t bother me, because it’s clearly linked to autoimmune shenanigans. Now with Graves’ disease, I also know that low TSH and increased thyroid antibodies are causing subclinical hyperthyroidism symptoms (such as occasional minor tremor, increased resting HR, among others) and Graves’ ophthalmology symptoms as a result of the thyroid antibodies. The low TSH and increased thyroid antibodies are a result of my immune system deciding to poke at my thyroid.

All this to say…I typically wonder less about “why” I have gotten these things, in part because the “why” doesn’t change “what” to do; I simply keep gathering new data points that I have an overactive immune system that gives me autoimmune stuff to deal with.

I have contrasted this with a lot of posts I observe in some of the online EPI groups I am a part of. Many people get diagnosed with EPI as a result of ongoing GI issues, which may or may not be related to other conditions (like IBS, which is often a catch-all for GI issues). But there’s a lot of posts wondering “why” they’ve gotten it, seemingly out of the blue.

When I do my initial research/learning on a new autoimmune thing, as I mentioned I do look for causal mechanisms to see what is known or not known. But that’s primarily, I think, to rule out if there’s anything else “new” going on in my body that this mechanism would inform me about. But 3/3 times (following type 1 diabetes, where I first learned about autoimmune conditions), it’s primarily confirmed that I have autoimmune things due to a kick-ass overactive immune system.

What I’ve realized that I often focus on, and most others do not, is what comes AFTER diagnosis. It’s the management (or treatment) of, and living with, these conditions that I want to know more about.

And sadly, especially in the latest two experiences (exocrine pancreatic insufficiency and Graves’ disease), there is not enough known about management and optimization of dealing with these conditions.

I’ve previously documented and written quite a bit (see a summary of all my posts here) about EPI, including my frustrations about “titrating” or getting the dose right for the enzymes I need to take every single time I eat something. This is part of the “management” gap I find in research and medical knowledge. It seems like clinicians and researchers spend a lot of time on the “why” and the diagnosis/starting point of telling someone they have a condition. But there is way less research about “how” to live and optimally manage these things.

My fellow patients (people with lived experiences) are probably saying “yeah, duh, and that’s the power of social media and patient advocacy groups to share knowledge”. I agree. I say that a lot, too. But one of the reasons these online social media groups are so powerful in sharing knowledge is because of the black hole or vacuum or utter absence of research in this space.

And it’s frustrating! Social media can be super powerful because you can learn about many n=1 experiences. If you’re like me, you analyze the patterns to see what might be reproducible and what is worth experimenting in my own n=1. But often, this knowledge stays in the real world. It is not routinely funded, studied, operationalized, and translated in systematic ways back to healthcare providers. When patients are diagnosed, they’re often told the “what” and occasionally the “why” (if it exists), but left to sometimes fall through the cracks in the “how” of optimally managing the new condition.

(I know, I know. I’m working on that, in diabetes and EPI, and I know dozens of friends, both people with lived experiences and researchers who ARE working on this, from diabetes to brain tumors to Parkinson’s and Alzheimer’s and beyond. And while we are moving the needles here, and making a difference, I’m wanting to highlight the bigger issue to those who haven’t previously been exposed to the issues that cause the gaps we are trying to fill!)

In my newest case of Graves’ disease, it presented with subclinical hyperthyroidism. As I wrote here, that for me means the lower TSH and higher thyroid antibodies but in range T3 and T4. In discussion with my physician, we decided to try an antithyroid drug, to try to lower the antibody levels, because the antibody levels are what cause the related eye symptoms (and they’re quite bothersome). The other primary symptom I have is higher resting HR, which is also really annoying, so I’m also hoping it helps with that, too. But the game plan was to start taking this medication every day; and get follow-up labs in about 2 months, because it takes ~6 weeks to see the change in thyroid levels.

Let me tell you, that’s a long time. I get that the medication works not on stored thyroid levels; thus, it impacts the new production only, and that’s why it takes 6 weeks to see it in the labs because that’s how long it takes to cycle through the stored thyroid stuff in your body.

My hope was that within 2-3 weeks I would see a change in my resting HR levels. I wasn’t sure what else to expect, and whether I’d see any other changes.

But I did.

It was in the course of DAYS, not weeks. It was really surprising! I immediately started to see a change in my resting HR (across two different wearable devices; a ring and a watch). Within a week, my phone’s health flagged it as a “trend”, too, and pinpointed the day (which it didn’t know) that I had started the new medication based on the change in the trending HR values.

Additionally, some of my eye symptoms went away. Prior to commencing the new medication, I would wake up and my eyes would hurt. Lubricating them (with eye drops throughout the day and gel before bed) helped some, but didn’t really fix the problem. I also had pretty significant red, patchy spots around the outside corner of one of my eyes, and eyelid swelling that would push on my eyeball. 4 days into the new medication, I had my first morning where I woke up without my eyes hurting. The next day it returned, and then I had two days without eye pain. Then I had 3-4 days with the painful eyes. Then….now I’m going on 2 weeks without the eye pain?! Meanwhile, I’m also tracking the eye swelling. It went down to match the eye pain going away. But it comes back periodically. Recently, I commented to Scott that I was starting to observe the pattern that the red/patchy skin at the corner and under my right eye would appear; then the next day the swelling of and above the eyelid would return. After 1-2 days of swelling, it would disappear. Because I’ve been tracking various symptoms, I looked at my data the other day and saw that it’s almost a 6-7 day pattern.

Interesting!

Again, the eye stuff is a result of antibody levels. So now I am curious about the production of antibodies and their timeline, and how that differs from TSH and thyroid hormones, and how they’re impacted with this drug.

None of that is information that is easy to get, so I’m deep in the medical literature trying again to find out what is known, whether this type of pattern is known; if it’s common; or if this level of data, like my within-days impact to resting HR change is new information.

Most of the research, sadly, seems to be on pre-diagnosis or what happens if you diagnose someone but not give them medication in hyperthyroid. For example, I found this systematic review on HRV and hyperthyroid and got excited, expecting to learn things that I could use, but found they explicitly removed the 3 studies that involved treating hyperthyroidism and are only studying what happens when you don’t treat it.

Sigh.

This is the type of gap that is so frustrating, as a patient or person who’s living with this. It’s the gap I see in EPI, where little is known on optimal titration and people don’t get prescribed enough enzymes and aren’t taught how to match their dosing to what they are eating, the way we are taught in diabetes to match our insulin dosing to what we’re eating.

And it matters! I’m working on writing up data from a community survey of people with EPI, many of whom shared that they don’t feel like they have their enzyme dosing well matched to what they are eating, in some cases 5+ years after their diagnosis. That’s appalling, to me. Many people with EPI and other conditions like this fall through the cracks with their doctors because there’s no plan or discussion on what managing optimally looks like; what to change if it’s not optimal for a person; and what to do or who to talk to if they need help managing.

Thankfully in diabetes, most people are supported and taught that it’s not “just” a shot of insulin, but there are more variables that need tracking and managing in order to optimize wellbeing and glucose levels when living with diabetes. But it took decades to get there in diabetes, I think.

What would it be like if more chronic diseases, like EPI and Graves’ disease (or any other hyper/hypothyroid-related diseases), also had this type of understanding across the majority of healthcare providers who treated and supported managing these conditions?

How much better would and could people feel? How much more energy would they have to live their lives, work, play with their families and friends? How much more would they thrive, instead of just surviving?

That’s what I wonder.

Wondering "how" rather than "why" of autimmune conditions, by @DanaMLewis from DIYPS.org

Graves’ Disease, Subclinical Hyperthyroidism, and Everything I Have Learned About It (So Far)

TLDR: I have newly diagnosed Graves’ Disease, I have associated eye stuff (called “Graves’ orbitopathy” or “Graves’ ophthalmopathy” or “thyroid eye disease”), subclinical hyperthyroidism, and a new learning curve. Below is what I’ve learned so far and what I’m still exploring.

As a person with type 1 diabetes (T1D) – which is an autoimmune disease – I am screened yearly for various high-risk related conditions. For example, celiac disease and thyroid issues, because those are fairly common in people with type 1 diabetes. I already have celiac disease (developed ~6 years after I developed T1D), but we have continued to screen every year in my annual blood work for thyroid markers, usually by screening T4 and TSH. Occasionally, T3 and/or TPO antibodies are also screened.

I remember vividly the chortle that my prior endocrinologist made after we diagnosed my celiac disease in college, probably in response to my comment about being frustrated of having “another” thing to deal with in addition to T1D. He chortled and said something like “once you have one (autoimmune thing), you’re likely to have two. Once you have two, you’ll be likely to have three.”

I didn’t like it at the time, and I don’t like it now. However, he’s not wrong. When your immune system has a little extra kick in it and you develop one autoimmune disease, the rates of having another autoimmune thing are increased. Thus, the typical yearly screening in T1D for celiac & thyroid.

I went 6 years between T1D and celiac, then almost 12-13 years to discover I now have exocrine pancreatic insufficiency (EPI). That’s not necessarily an autoimmune thing but may be a side effect of long-term T1D. Regardless, I was still thankful for the long period of time between T1D and celiac, then T1D+celiac and EPI. I was assuming that something else was coming eventually, but that I’d likely have a few years before the shoe dropped.

Nope.

I wasn’t terribly surprised when I scheduled my annual endocrinology appointment and did my annual blood work to find that one of my thyroid values was off. Specifically, my TSH (thyroid stimulating hormone) was low / below normal range. However, my T4 was smack dab in the middle of normal range. I got my blood work back Tuesday and waited for my virtual appointment on Friday to discuss in detail with my endocrinologist.

Since I’m me, I was curious about the interplay between normal thyroid levels (T4, and I suspected my T3 was likely still in range) but a low TSH value. What did that mean? General consensus seems to define this as “subclinical hyperthyroidism”. It’s not always treated, unless you are older (>65), have osteoporosis or heart disease, or TSH levels are <0.1.

I’m <65, don’t (as far as I know) have osteoporosis or heart disease, and my TSH levels are between 0.1 and 0.4, which is the low end of the normal range. So general treatment guidelines (see this example from the AAFP) suggest treatment isn’t necessarily warranted.

However…there’s more information that factors into the decision making. First, I had my last annual eye exam in October. All was well. Yet in November, I developed really gritty, dry eyes and went in for an appointment. I was diagnosed with dry eyes (gee, thanks!) and recommended to use gel drops at night before bed and regular eye drops during the day as needed. I did end up needing eye drops several times every day.

Then at the end of December or early January, we realized I had exocrine pancreatic insufficiency (EPI). I had been wondering if my dry eyes was related to the lack of digestion and absorption of nutrients, which also influences how my body uses the water content from food. It did seem to get a little better in the following months, because while I still needed the eye gel at night, I eventually moved to several days a week where I didn’t seem to need the eye drops during the day – yay!

However, in February and early March, I started to physically notice a shift in my resting overnight heart rate (HR). My Pebble 2+ HR watch and my Oura ring, both of which measure HR and heart rate variability (HRV), confirmed that both metrics were getting worse. I had a slowly increasing overnight HR and associated decrease in HRV. I am used to fluctuations, because the intensity of my ultrarunning can also influence HR the next day as a signal for whether my body has recovered yet or not. But instead of a day or two of increased numbers, I had an increasing trend line over several weeks, and it started to physically become bothersome. I actually raised the idea of getting my thyroid blood work done early this year, and was about to request the lab work, when after ~6 weeks or so the trend seemed to reverse and things (HR-wise) went back to “normal” for me.

Then I broke my toe in July and the same thing happened, but I chalked it up to sleep disruption from the pain and recovering from the fracture. My HR was continuing to rise even as the pain subsided and my toe was clearly healing. And looking back at my HR data, I can see it actually started to rise at the beginning of July, about two weeks before I broke my toe, so it’s not solely influenced by my broken toe.

As a result of these HR increases (that are noticeable and bothersome because I’m also not sleeping well at night and I physically feel the higher HR during the day), and the ongoing dry/gritty eyes, I suspected that the cause of my “subclinical hyperthyroidism” was Graves’ disease.

I’ve seen estimates that ~30% of people with Graves’ disease have what is called “Graves’ orbitopathy” (and other estimates suggest 20-50%, like this one), so the combination of my ongoing eye symptoms and the low TSH suggested that further lab work assessing various thyroid antibody levels would be able to confirm whether Graves’ disease was the likely source of the subclinical hyperthyroidism.

Therefore, I wasn’t surprised during my virtual visit that my endocrinologist ordered additional labs (repeat of T4 and TSH; adding in T3, TPO antibodies, and TSI (Thyroid Stimulating Immunoglobulin), Thyrotropin Receptor Ab, and Thyroglobulin Ab). Treatment plan, if any, would be based on these results.

I managed to get in that (Friday) afternoon for the repeat lab work, and my results started trickling in by the time I woke up Saturday morning. First, T3, T4, TPO, and TSH came back. T4 was still normal; as I expected, T3 was also normal. TPO antibodies were high, as expected, TSH was still low, as I expected. Saturday night, Thyroglobulin Ab came back high, as expected. Monday, TSI came back high, as expected. Tuesday, my last test result of Thyrotropin Receptor Ab came back, also high as expected.

The summary was: all antibodies high; TSH low; T3/T4 normal.

My endocrinologist messages me Tuesday afternoon confirming mild Graves’ disease with subclinical hyperthyroidism.

The challenge is that I have normal T3/T4 levels. If those were high, we’d treat based on those levels and use those levels coming back into normal range and any change in antibody levels to assess that things were going well.

But the guidelines for subclinical hyperthyroidism don’t really indicate treatment (except on an individual level based on age, other conditions, or undetectable TSH <0.1, as I mentioned).

However, from what I’ve read, the “eye stuff” seems to be driven not by thyroid levels but by the presence of the increased thyroid antibodies. Treatment would possibly bring down the thyroid antibody levels, which might help with the eye disease progression. But not a guarantee. So my doctor left it up to me to decide whether to treat it or not.

Given the ongoing presence of active eye disease (I haven’t been able to wear my contacts for two weeks right now due to swelling/pain in the eyes, plus itching and redness), and the bothersome heart rate feeling, I have decided to try antithyroid medication. I’ll be on a relatively low dose of an “antithyroid” drug, again with the goal of trying to reduce my antibody levels.

This is why I ended up deciding to write this blog post after all: I have not been able to find any clear treatment guidelines for subclinical hyperthyroidism and Graves’ disease with active eye symptoms (from Graves’ orbitopathy). The literature does suggest that treatment to reduce thyroid antibodies even with in-range T3 and T4, targeting a return to normal TSH levels, may be helpful in reducing Graves’ orbitopathy symptoms. This isn’t well known/established enough to have been documented in treatment guidelines, but does seem to occur in many people who are treated.

So hopefully, anyone else with low TSH and high antibodies suggesting Graves’ disease but normal T3 and T4 levels that suggests subclinical hyperthyroidism and also has other symptoms (whether that’s heart rate or other common hyperthyroid symptoms like increased sweating, shaking, heart palpitations, heat intolerance, sleep disturbances) that are bothersome, now have an example of what I chose, given my situation as described above.

I also thought sharing my question list at different stages for my endocrinologist would be helpful. After I saw that I had low TSH and in range T4, and suspected this meant I had subclinical hyperthyroidism from Graves’ disease, given my eye symptoms, the questions I asked my endocrinologist were:

  • What additional lab work did we need to confirm subclinical hyperthyroidism and Graves’ disease as the cause? What additional information or lab work would give us a treatment plan?As expected, he repeated TSH and T4, added T3 and TPO and the other antibody tests described above: TGAb, TRab, TSI. This would confirm subclinical hyperthyroidism and Graves’ as the likely source.

     

  • Do I need treatment, since the guidelines generally don’t suggest treatment with normal T3/T4 and TSH between .1 and .4?Initially he suggested treatment would be an option, and after the repeat and expanded lab work, left it up to my decision. Given my symptoms that are actively bothering me, I’m choosing to try low-dose antithyroid medication.
  • For hyperthyroidism treatment, beta blockers seem to be part of treatment guidelines for managing symptoms in the short-term, since it takes ~6 weeks for antithyroid medication to show up in lab results. Were beta blockers warranted in my case?My endo typically doesn’t like to prescribe beta blockers unless there are extreme symptoms. He gave an example of someone with a T4 (I think) around 10 and extreme visible shaking. He left it up to me, but his opinion was the side effects, such as lethargy, would outweigh the benefits for mild symptoms, so it is better to treat the root cause. I agreed and did not ask for a beta blocker prescription.
  • I also asked if a DEXA scan was warranted to check my bone density.I haven’t had one in over a decade, and celiac and EPI and now Graves’ puts me at possible higher risk of bone density issues. And, since the presence of osteoporosis changes the treatment recommendation for subclinical hyperthyroidism, we agreed it was worth doing. I have it scheduled in a few weeks. My last one over a decade ago was normal.
  • Finally, I asked about my eye care, now that I have a known eye thing (Graves’ orbitopathy). Do I need to get referred to an ophthalmologist, or can I continue to see my existing optometrist for annual eye care (including diabetes eye exam) and contact fittings?My endocrinologist suggested that my optometrist can continue to manage my eye care, unless something changes significantly. Ophthalmologists, based on his response and my research, seem to handle severe eye disease treatments that aren’t likely warranted for me. I’ll probably need supportive eye care (e.g. gel drops, regular eye drops) for now. However, I’m planning to send a note to my eye doctor and flag that I want to talk about Graves’ eye things and a plan for monitoring severity and progression over time, and check whether she’s comfortable supporting me or if she prefers to refer me to someone else. 


After my repeat labs came back, my endocrinologist messaged me to confirm things and ask if I wanted him to send in the prescription as previously discussed. This exchanged answered the additional questions I had at this time:

  • What is the treatment timeline? How soon might I see results?He suggested repeat labs at the 2 month mark. Ideally, we’d see reduced antibody levels and my hope is that my eye symptoms will have also improved and/or I won’t have any additional weeks without being able to wear contacts.

    Given I have a clear impact to my heart rate, I’m hypothesizing that I might see changes to the trend in my heart rate data sooner than 6 weeks – 2 months, so that’ll be interesting to track!

     

  • Side effects?Common side effects with antithyroid drugs are rash/allergic type response, headache, or agranulocytosis. He told me to discontinue and contact the office if I had any of those symptoms.

    He didn’t go into detail, but I’ve read about agranulocytosis and it seems like if you have a fever and strong sore throat, you need to discontinue and probably will have blood work ordered to make sure your white blood cell counts are ok. Don’t google too much on this one as it sounds scary, but it’s also rare – less than 2% of people seem to have this.

     

  • The only question he didn’t answer was whether it makes a difference in efficacy to take the antithyroid drugs at night or in the morning.Probably, the answer is it doesn’t matter, and whatever time you can take it consistently is best. However, I want to optimize and get the best results from taking this, so I’m bummed that there doesn’t seem to be any evidence (let me know if you’ve found anything in medical literature) suggesting how to optimize timing of it. 

So that’s where I am today.

I now have type 1 diabetes, celiac disease, exocrine pancreatic insufficiency, and Graves’ disease (contributing to subclinical hyperthyroidism). It’s possible that we can fix the subclinical hyperthyroidism, and that I won’t need to be on antithyroid medication long-term. However, the data for those of us with Graves’ orbitopathy isn’t super optimistic compared to those without Graves’ eye disease; so I am managing my expectations that managing my thyroid antibody and hormone levels will be an ongoing thing that I get to do along with managing insulin and blood sugars and managing pancreatic enzymes. We’ll see!