If you are familiar with the Star Wars franchise, you know there is a “light side” and a “dark side” of the force. These sides represent either the selfless or the selfish and essentially act to hold the galaxy together. If you consider our galactic friends and their adventures for a second, you may be able to see there is a large parallel between the galaxy and the human body. After all, the goal for all Jedi is to keep the force within balance, or in the context of the human body and for our purposes, within homeostasis. So then, what happens when your body or the galaxy is no longer in homeostasis? Well, if you go back to our simplified analogy, you’ll find it suggests some aspect within our complex body has pulled a ‘Darth Vader’ and gone to the dark side… which can predictably have devastating consequences. This Star Wars analogy is also a stellar example for the pathogenesis of cancer: a cancerous cell is in essence simply a “Darth Vader cell”, but we will dive further into cancer a couple weeks from now (so stay tuned).
The thyroid gland is situated at the base of the neck and plays an important role in metabolism and development within the human body1. The thyroid is glandular in nature (meaning it secretes hormones) and therefore can be categorized under dysfunctions of the endocrine system. Specifically, we can identify the type of dysfunction or disease by looking a little closer at where exactly regulation goes haywire. Regulation of the thyroid occurs through the hypothalamic-pituitary-thyroid (HPT) axis1. It is important to understand the HPT axis encompasses the hypothalamus, anterior pituitary and thyroid gland which also stores the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine)1. An appropriate feedback loop for the HPT axis is illustrated below:
As annotated in the figure, the hypothalamus releases thyrotropin-releasing hormone (TRH) allowing for positive feedback to the pituitary gland. The pituitary gland then produces thyroid-stimulating hormone (TSH) allowing for positive feedback to thyroid gland. Lastly, the thyroid gland produces T3 and T4 allowing for negative feedback on hypothalamus and pituitary gland to decrease levels of TRH + TSH (homeostasis and balance is now upheld within the body). Notice how TRH and TSH are regulated through the negative feedback loop? In the context of a thyroid gland, an appropriate regulation of homeostasis like the example above would be referred to as “euthyroid”, meaning everything is working as it should and the force is in balance. When the force is unbalanced, we hit situations of “hypothyroidism” and “hyperthyroidism” where your glands officially go to the dark side. The good thing about thyroid dysfunction is these processes are entirely predictable if you understand what goes wrong in what part of the loop.
In hypothyroidism, you have low levels of T3 and T41. We can predict decreased levels of both T3 and T4 leads to an increase in both TSH and TRH to ‘amp’ up the loop. However, Hashimoto’s disease is an example of an autoimmune condition where antibodies essentially destroy the thyroid gland (Hashimoto’s is typical of primary hypothyroidism)1. Destruction of the thyroid gland will cause decreased levels of both T3 and T4 leading to increased levels of TSH and TRH but because the gland is destroyed, an increase in TSH and TRH does not work, and thyroid hormones remain low. In this case, patients are typically exogenously supplemented with medications such as levothyroxine since their endogenous production is impaired.
In hyperthyroidism, you have high levels of T3 and T41. Again, we can predict that an increase in both T3 and T4 will lead to a decrease in both TSH and TRH in an attempt to slow down the loop. However, Graves’ disease is another example of an autoimmune condition where antibodies stimulate the gland to produce more hormones (Grave’s disease is typical of primary hyperthyroidism)1. Stimulation of the thyroid gland causes increased levels of both T3 and T4 leading to decreased levels of both TSH and TRH to try and slow down hormone production. However, since the gland is being stimulated by the antibodies regardless, T3 and T4 levels remain elevated.
Notice how in both cases of primary hyperthyroidism and primary hypothyroidism, the negative feedback loop is still trying to work, it just does not matter because there is an autoimmune issue with the gland itself. So, although the negative feedback loop is still there, the process fails due to either the destruction or dysfunction of the gland itself. In other words, if we go back to our analogy the light side is still there and trying to restore balance to the force, but it does not matter because the glands themselves have gone to the dark side. I hope our little galactic journey through primary thyroid disorders has been informative and helpful for your studies. All the best!
- Kane M.P., & Bakst G (2020). Thyroid disorders. DiPiro J.T., & Yee G.C., & Posey L, & Haines S.T., & Nolin T.D., & Ellingrod V(Eds.), Pharmacotherapy: A Pathophysiologic Approach, 11e. McGraw-Hill. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2577§ionid=223397495