Thyroid Disorders - Bullet With Butterfly Wings
The thyroid is a butterfly-shaped gland. But for some, it can be more like a bullet to the neck. The number of systems that our thyroid helps regulate truly is incredible, and an over or under-active thyroid can cause a whole host of acute and chronic issues.
On the one hand, imagine a patient who has a thyroid history and is cold, weak, and has a depressed level of consciousness. Why is this occurring, and what's the diagnosis and treatment? On the other hand, imagine an anxious, hyperpyrexic patient in atrial fibrillation. Both patients have thyroid issues, but why do these patients present so differently?
Let's see what happens when the scales tip either way for a few of the systems that the thyroid helps control!
A drawing of the general anatomy of the thyroid
A Quick Refresher
Let's start by briefly going over the mechanisms that get the thyroid to secrete thyroid hormone. Below is a good ol' google image copy and paste of how thyroid hormone is synthesized, but I over-simplify it in the following paragraph. This first part seems a little dense because we never talk about any of these mechanisms as emergency providers. 😂
Just make sure you start at "Blood" 😳
This paragraph is rough... 🤷🏼
Essentially... ioDIDE (-) gets oxidized... Meanwhile, the endoplasmic reticulum in a thyroid follicle makes this protein called thyroglobulin. That thyroglobulin is getting kicked into an area where that oxidized iodide (now iodine) goes through iodination and meets up with the thyroglobulin. The thyroglobulin then get iodine attached at particular sites - some sites get 3, others get 4. This thyroglobulin goes back into the cell and is lysed (chopped up) by lysosomes. The process of cutting the thyroglobulin into pieces isolates those areas that got 3 and 4 iodines. These chopped-up parts are called T3 and T4. T3 and T4 are the portions interpreted by cells and cause the action at the target organ! T3 is like T4, except it's missing iodine at its 5' (five prime) site. T4 is also called thyroxine, and T3 is also called Triiodothyronine (try-eye-ode-oh-thigh-row-neen). If you look at the bottom right corner of the graph, you'll see the iodine attached to the old parts of the thyroglobulin. T4 can turn into T3 through deiodination (the removal of one iodine). Most thyroid hormone that leaves the thyroid is T4, which is less potent than T3. T4 gets converted to T3 in cells when needed (Shahid, 2021). When we hear about T3/T4 levels, this is why. If you're like me, you can't continue until you know a little about the process, so there was a brief overview for those of you who need the same thing.
A simplified version of the graph above
This (overly) simplified graph sums it up as:
Iodide comes in and gets turned into iodine.
Thyroglobulin is there.
Those two meet up on a 'chain.'
Lysosomes chop up that chain into parts called T3 and T4.
T3 and T4 move into the blood, where they go to the whole body.
And at any of those steps, you could add, 'and some other stuff happens.' But, I think this is good for now.
Higher-up control of the thyroid is pictured here:
A common graph describing TSH/TH levels in various pathologies
Alright, that's about all the overview we need, and if you get lost later, refer back to the beginning. Let's take a look at goiters and then organ systems!
What's With the Goiter?
A goiter is an enlarged thyroid gland. In the picture above, it's pretty cool because you can see (especially in the middle and right images) almost the exact shape of the thyroid! One interesting point I found in researching goiters was that goiters could extend down behind the sternum, enter the mediastinum, and even show up on chest films. Check out this image that I found on research gate.
It takes a second to decode the legend on this image, but it's worth appreciating how far down that goiter is! In image C (lower left), the "b" is the goiter, and the "c" is the aorta. It isn't hard to imagine why this can happen:
This patient is blocking the venous return from his head by raising his arms - a condition known as superior vena cava syndrome. Note the visible goiter in the first image. This goiter has some internal growth, and it's pressing on all kinds of internal structures in the neck and mediastinum.
Several muscles overlay the thyroid.
Cranial-facing view of the thyroid.
The thyroid can grow out of control for several reasons. We're primarily concerned with Grave's disease and Hashimoto's thyroiditis in North America, but there are other places in the world where iodine deficiency is the leading cause of a goiter. This is actually why we have iodized salt - to provide iodide (which produces iodine in the thyroid) to populations who lack proper nutrition through the available diet.
"This salt supplies iodide, a necessary nutrient."
The causes of goiter are not always so pathological, however. A thyroid may... enlarge. Interestingly enough, the size of a goiter does not tell us if this indeed is the problem with the patient. A patient may have an enormous goiter and not have any actual endocrine emergency. At the same time, a patient may have a goiter that is practically nonexistent but still causing severe symptoms. Other causes such as cancer and infection can also cause the thyroid to enlarge (Can, 2021).
Check out this graph that contrasts hyper and hypothyroidism.
Looking at what happens when the thyroid is either underactive or overactive, we get a pretty good idea of what the thyroid does typically. Going in line with the
Cold or heat intolerance? = body temperature regulation
Fatigue and restlessness or bulging eyes? = wakefulness
Slow and weak or fast and strong heart? = cardiovascular actions
Lethargy or tremors? = nervous system activity
Constipation or diarrhea? = GI activity
Decreased or increased metabolism? = energy consumption or storage
These items loosely fit into the '3M' model of thyroid actions.
That's a lot of stuff - and that's because thyroid hormone has an action on every cell in the body. All of the effects of thyroid via T3/T4 seem to center around energy consumption - metabolism and the things that result from it. Take low for an example:
The patient with hypothyroidism - perhaps from Hashimoto's Thyroiditis (Mincer et al., 2020) - is always cold, everything is tired and lethargic, and even the cardiovascular and GI systems move slowly and weakly through their paces. Hashimoto's is an autoimmune condition in which the immune system attacks the thyroid. You could probably imagine that a patient like this would slow down until they became comatose... Well, that's a very astute observation since this condition would be called Myxedema Coma ;) Myxedema coma results from deficient circulating levels of T3/T4, slowing the whole system down into a coma (Elshimy, 2021). What about an example of a high-functioning thyroid?
A hyperthyroid patient - perhaps due to Grave's disease (Pokhrel, 2021) - is always hot, their eyes are bulging, they're shaking, and even the cardiovascular (tachycardia+hypertension) and GI (diarrhea+cramping) systems are moving very quickly. Grave's disease also involves the immune system but makes an antibody that causes thyroid stimulation. Let's think of the worst-case scenario for this patient as well. They would eventually get so overly stimulated that they would suffer from the side effects of tachycardia, hypertension, dehydration, and panic. This end of the spectrum of hyperthyroidism is called Thyroid Storm. Thyroid Storm results from a systemic overload of T3/T4, speeding up the entire system into a chaotic storm-like state (Pokhrel, 2021).
That seems to put both ends of the spectrum in a nice little bow, but there is a catch with the thyroid storm patients - their high metabolism can only last so long. They can become so unstable that they enter decompensated shock and look more like myxedema coma patients. This is much like a tachyarrhythmia we might see. The system is overstimulated but can no longer maintain such high activity levels and starts to go towards the other extreme.
Even though thyroid hormones are everywhere, it's good to zoom in on just a few organ systems and the nuances we can find there. We'll touch on just some high points for the cardiovascular, nervous, and endocrine systems.
The graph above probably doesn't contain too many surprises since most of it is perhaps what we expected from either side of the thyroid spectrum when the patient becomes rather sick. However, the afterload / systemic vascular resistance seems backward.
We would naturally think that the afterload would be high in hypERthyroidism since that seems to fit the trend of tachycardia and hypertension. With hypOthyroidism, we would likely expect the opposite, in which afterload would be low and follow the trend of bradycardia and hypotension. However, as we see from the graph above, the opposite is true. Why does this occur counterintuitive SVR change occur?
Hypothyroid usually presents with hypertension (Berta, 2016), specifically a high diastolic blood pressure. However, as they become more sick and unstable, they will regress into hypotension. We usually see this diastolic hypertension and increase in afterload in the hypothyroidism patient partially due to cholesterol and aortic stiffening and partly due to decreases in nitric oxide secondary to endothelial dysfunction (a lack in the ability to dilate). This is the opposite in hyperthyroidism, where the thyroid hormone acts to relax peripheral arteries, resulting in decreased afterload. To sum that up, Cai et al. (2015) note:
"Hypothyroidism impairs endothelium-dependent dilatations, while hyperthyroidism augments the production of endothelial nitric oxide."
There are more mechanisms than that, but that statement covers the general idea. Looking at the patient as a whole, how are all of these cardiac symptoms treated?
Severe HypERthyroidism (~Thyroid Storm territory)
Beta-blockers are usually used to treat tachycardia and hypertension. There are a variety of medications that can be used, but esmolol and propranolol seem to be the most commonly seen in guidelines. If the patient has reactive airway disease like asthma, a cardioselective agent like metoprolol might be used, or perhaps even a benzothiazepine such as diltiazem if beta-blockers are contraindicated.
Other treatments are mainly aimed at reducing the conversion of T4 to T3 since T3 is the version of thyroid hormone that is causing the issues (it is by far the more active and potent of the two). Examples of medications that might be used to control this process are thionamide, iodine solutions, glucocorticoids (usually in life-threatening cases), and bile acid sequestrants (Satoh, 2016).
HypOthyroidism (~Myxedema Coma territory)
These patients need T4/T3. T4 is administered as levothyroxine, and sometimes T3 is also given in supplement form (levothyroxine and triiodothyronine can be given IV). Steroids are also used if adrenal insufficiency is suspected excluded as a diagnosis.
As for the rest of the cardiovascular symptoms in hypothyroidism, they're treated based on presentation with traditional therapy. Since the patient may need inotropic and chronotropic support (heart rate and contraction strength), perhaps epinephrine would be appropriate. Thyroid hormone stimulates the synthesis of B1 receptors, so in hypothyroidism, there is less synthesis/sensitivity to B1 stimulation - so they need extra help from inopressors (Elshimy, 2021).
The thyroid hormone is key to stimulating neurological development in the nervous system. Thyroid hormone stimulates dendrites, myelin, and synapses. Those changes take time, but they're noticeable in the level of consciousness changes we see in high and low levels of thyroid hormone.
Suppose the patient is severe enough hypothyroidism to be in a myxedema coma-like state or has severe enough hyperthyroidism to be in Thyroid Storm. In that case, they will likely present neurologically how you would expect. However, there can be some challenges to relying on this presentation. We mentioned earlier that the Thyroid Storm patient will eventually deteriorate, become uncompensated, and likely mimic what we would expect from a Myxedema Coma patient. The Myxedema Coma patient can also present a little like the Thyroid Storm patient as they lead up to coma, by presenting something called "Myxedema Madness". Speaking on Myxedema Madness, Parikh, (2014) notes that "the psychiatric symptoms range from inattentiveness, lethargy, affective abnormalities, delusions, hallucinations, and delirium. At times, the behavior abnormalities are so striking that a patient is first diagnosed with primary psychiatric disturbance rather than hypothyroidism"
Treatment for these patients is also based on symptoms and presentation. Either patient with anxiety would get treated as such (perhaps with benzodiazepines), and the patient with a decreased level of consciousness might need airway protection and assistance with oxygenation and ventilation.
Thyroid function plays a major role in our metabolism. This leads us to wonder if glucose balance could be deranged in these patients. I know what you're thinking... if the patient has an altered level of consciousness, we're already going to be checking their blood glucose. You're right - regardless of the etiology, we would very likely discover abnormal blood glucose in these patients (Potenza, 2009). However, what our blood glucose monitor shows us, either way, could lead us towards a diagnosis.
Hypoglycemia is more common in hypothyroid patients (along with hyponatremia). Another endocrine/metabolic item that is very important to remember in hypothyroidism is hypothermia. These patients need to be warmed, and their hypothermia should not be exacerbated by failing to cover them up with blankets, or administering amounts of cold (room temperature) fluids (Elshimy, 2021).
Hypoglycemia is much less common in hyperthyroidism patients. In fact, the hyperthyroidism patient may have a higher serum glucose reading. Also contrasting the hypothyroidism patient, they're hot - perhaps up to 104 - 106º f (Pokhrel, 2021).
Thyroid disorders to the extent and severity where they cause thyroid storm or myxedema coma are reported in the literature as rare events. Is this because it sometimes goes unnoticed or misdiagnosed? I'm not sure, but it no doubt happens from to time. However, what I do know is that we don't spend very much time learning these conditions in EMS at all, so we are very likely to misdiagnose these patients. And, it's not like thyroid issues are uncommon. The Cleveland Clinic reported that thyroid disease is "very common", and about 20 million Americans have been diagnosed with thyroid disorders (and women outweighed men in this number by 5-8x). By familiarizing ourselves with thyroid disorders from time to time, we'll be ready to recognize and treat these patients when we find them. Like Louis Pasteur once said:
"Chance favors only the prepared mind."
Thanks for reading!
Shahid MA, Ashraf MA, Sharma S. Physiology, Thyroid Hormone. StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK500006/
Can AS, Rehman A. Goiter. [Updated 2021 Aug 30].2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562161/
Alkabban FM, Patel BC. Nontoxic Goiter. 2021 Jan-.Available at:https://www.ncbi.nlm.nih.gov/
Perez-Montiel, M. D., & Suster, S. (2008). The spectrum of histologic changes in thyroid hyperplasia: A clinicopathologic study of 300 cases. Human Pathology, 39(7), 1080–1087. https://doi.org/10.1016/j.humpath.2007.12.001
Mincer DL, Jialal I. Hashimoto Thyroiditis. [Updated 2021 Sep 28]. In: StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459262/
Pokhrel B, Bhusal K. Graves Disease. [Updated 2021 Jul 21]. In: StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448195/
Pokhrel B, Aiman W, Bhusal K. Thyroid Storm. [Updated 2021 Jul 21]. In: StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448095/
Elshimy G, Chippa V, Correa R. Myxedema. [Updated 2021 Oct 1]. In: StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545193/
Cai, Y., Manio, M. M., Leung, G. P., Xu, A., Tang, E. H., & Vanhoutte, P. M. (2015). Thyroid hormone affects both endothelial and vascular smooth muscle cells in rat arteries. European journal of pharmacology, 747, 18–28. https://doi.org/10.1016/j.ejphar.2014.11.036
Berta, E., Lengyel, I., Halmi, S., Zrínyi, M., Erdei, A., Harangi, M., Páll, D., Nagy, E. V., & Bodor, M. (2019). Hypertension in thyroid disorders. Frontiers in Endocrinology, 10. https://doi.org/10.3389/fendo.2019.00482
Satoh T, Isozaki O, Suzuki A, et al. 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition). Endocr J 2016; 63:1025.
Milner MR, Gelman KM, Phillips RA, et al. Double-blind crossover trial of diltiazem versus propranolol in the management of thyrotoxic symptoms. Pharmacotherapy 1990; 10:100.
Parikh, N., Sharma, P., & Parmar, C. (2014). A case report on myxedema madness: curable psychosis. Indian journal of psychological medicine, 36(1), 80–81. https://doi.org/10.4103/0253-7176.127260
Potenza, M., Via, M. A., & Yanagisawa, R. T. (2009). Excess thyroid hormone and carbohydrate metabolism. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 15(3), 254–262. https://doi.org/10.4158/EP.15.3.254