Unrelenting fatigue in patients with Hashimoto’s thyroiditis, despite “normal” thyroid functions tests is an extremely common complaint in my patient population, many of whom have Chronic Fatigue Syndrome. Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a debilitating condition characterized by severe, unexplained fatigue that lasts for at least six months and is not improved by rest. It often comes with a myriad of other symptoms, including muscle pain, cognitive difficulties, and sleep disturbances. Despite its significant impact on the lives of those affected, CFS remains poorly understood and effective treatments are limited. However, recent research has shed light on a potential link between CFS, selenium, and thyroid hormones, opening new avenues for understanding and managing this enigmatic condition.
Yet Another Antibody that Affects Thyroid Function
I recently came across some research by Sun and colleagues that sheds light on why the fatigue for CFS patients with Hashimoto’s might be unrelenting. Interestingly, in 2021 Sun’s research group discovered a new autoantibody that affects thyroid function. Their research verified their hypotheses that the body has natural autoantibodies to the selenium transporter selenoprotein P (SELENOP) in thyroid patients which impair selenium transport and thus negatively affect glutathione production in the thyroid, which is so essential to help protect the thyroid from the oxidative stress that occurs in the thyroid with thyroid hormone production. Their most recent research from 2023 unveiled a fascinating connection between CFS and selenium in the form of autoantibodies targeting selenoprotein P (SELENOP-aAb). [CORRECTION] They discovered that there is a subset of patients with chronic fatigue syndrome with autoantibodies to selenoprotein P (SELENOP-aAb) which hinders normal transport of selenium to target tissues and causes reduced selenoprotein expression [in my originally blog I misstated that these patients not also had Hashimoto's thyroiditis, which the article does indicate - there was no mention if they screened or excluded participants with Hashimoto's]. This disruption had far-reaching consequences on the health of CFS patients.
Selenium Connection
To understand their findings, we need to understand the connection of selenium to thyroid function. Selenium is a trace element that plays a crucial role in various physiological processes within the body. It is an essential component of selenoproteins, a family of proteins that function as antioxidants and help regulate the immune system and thyroid hormones. Selenium helps to protect the thyroid from oxidative stress that occurs normally during thyroid hormone production. If selenium isn't able to be properly transported, oxidative stress and tissue damage ensues and thyroid (and body) cannot function optimally.
Thyroid Hormones and the Impact on Chronic Fatigue Syndrome (CFS)
To fully grasp the implications of SELENOP-aAb in CFS, researchers examined the interplay between selenium, selenoproteins, and thyroid hormones (TH). The thyroid gland produces TH, essential for regulating metabolism, energy production, and overall health. Thyroid hormones come in two primary forms: T4 (thyroxine) and T3 (triiodothyronine). T3 is an active thyroid hormone that has metabolic effects in our body and derives from T4 (inactive thyroid hormone) through a process known as deiodination 1 (DIO1) and deiodination 2 (DIO2). DIO1 occurs mostly in the thyroid, but also in the liver and kidneys, whereas DI02 activity has been detected in areas of the brain (pituitary and hypothalamus), ear (cochlea), brown adipose tissue, bones, muscles, heart, and central nervous system. The T3 produced by DIO2 in these peripheral tissues persists longer in the body for reasons that are not yet fully understood. We also have DIO3 which helps to protect fetal tissues and adult brains (central nervous system) from excessive TH production by converting T4 to inactive reverse T3 (rT3) and T3 to inactive 3,3’-diiodothyronine (T2).
Sun et al introduced two indices to evaluate thyroid gland activity and peripheral deiodination: the SPINA GT index (secretory capacity of the thyroid gland, indicates DIO1 activity) and the SPINA GD index (total deiodination activity, indicates peripheral tissue DIO2 activity). These indices offer valuable insights into how SELENOP-aAb impacted TH metabolism. Patients with SELENOP-aAb displayed lower SPINA GD values, indicating reduced TH activation as well as lower active thyroid hormone (fT3) levels and higher levels of inactive thyroid hormone (rT3). Furthermore, their 24-hour urinary iodine concentrations were significantly lower, pointing to suppressed TH deiodination. This collective evidence suggested that SELENOP-aAb disrupted regular selenium supply to target tissues, resulting in reduced selenoprotein expression, elevated oxidative stress, and impaired TH activation.
Sun et al’s 2023 study is frankly one of the most useful studies on thyroid function that I’ve come across. It sheds so much light onto several different and previously perplexing aspects of thyroid health. Clinically, I tend to recommend 24-hour urine iodine testing to my hypothyroid patients who upon dietary review have a low iodine diet. However, this study helps us understand that iodine levels can be low in patients even with adequate dietary intake because of the SELENOP antibodies making it so iodine cannot be freed from the tissue. Thus, 24-hour urinary iodine might be a helpful test for all patients with Hashimoto’s thyroiditis and if low in a patient with normal iodine consumption, may point towards SELENOP-aABs. Their findings also help to explain why supplementing with high dose iodine in patients with Hashimoto’s can go south for some patients. I’ve never had clinical success with this approach – iodine is very oxidizing to thyroid tissues, especially in the context of low selenium, and there is even more oxidative stress with SELENOP-aABs which creates a functional iodine deficiency. Iodine is like fuel to the fire in this situation. Furthermore, their study helps us better understand why selenium supplement is vital for patients with Hashimoto’s but is not a cure-all in this situation. Other studies have demonstrated that selenium supplementation helps to improve thyroid function and lower thyroid antibodies in patients with Hashimoto’s for several months but without significant improvements after this. Repletion of selenium helps to counter the oxidative stress from SELENOP-aAB, but may not resolve the SELENOP-aABs, this research hasn’t yet been done. Deficiencies of selenium and iodine we may see with SELENOP-aABs appear to be functional and related to these autoantibodies. Finally, this study helps us to better understand why some patients do so much better while on active thyroid replacement than others, particularly those with chronic fatigue syndrome, as their peripheral conversion of inactive (T4) to active thyroid (fT3) is impaired by SELENOP-aAB lending to more brain fog and bodily fatigue.
Implications and Future Directions
The discovery of SELENOP-aAb in a subset of CFS patients opens a promising avenue for understanding and managing this perplexing condition. It suggests that CFS may have an autoimmune component that affects selenium transport and thyroid hormone metabolism, leading to characteristic symptoms of fatigue, pain, and cognitive dysfunction. While naturopathic doctors have long appreciated the nuances of thyroid function in different patients, and that a personalized approach is needed, we didn’t understand all the whys. I was excited to see if SELENO-Abs and SPINA GD discussed in Sun et al’s study, were available through standard commercial medical labs, sadly they are not yet available. I expectantly await additional research with larger study groups and more longitudinal studies that will hopefully pave the way for additional commercially available tests that can help clinicians better understand the nuances of thyroid function in individual patients and more targeted approaches to underlying immune dysfunction.
An Aside - Bio-Energetic Testing!
As an aside, while I was writing this blog this week, another interesting study on chronic fatigue syndrome came across my newsfeed on a blood-cell based diagnostic test for chronic fatigue syndrome that appears to have extremely high accuracy.
Given that so many patients with CFS go through the ringer prior to getting a diagnosis, often being told their symptoms are “all in their head”, obtaining access to an accurate diagnostic test would be a game changer for these patients. The method of testing, called single-cell Raman spectroscopy (SCRS), measures the vibrations of the cell providing a type of energetic fingerprinting of all the biomolecules in the cell. Vibrational energy is being found to help identify imbalances at a cellular level - amazing, right?! Different types of bio-energetic testing and balancing machines (ie EKG, heart rate variability, TENS, etc) have been available for some time, but this is the first time I’ve seen such technology aid in diagnosis so specifically and at a cellular level. As energetic beings, it makes so much sense that medical research is beginning to look at energetic vibrations to provide additional insights on underlying cell function and aid in the diagnosis, monitoring and potentially treatment of disease.
Dr. Sarah Giardenelli is a naturopathic doctor, herbalist, acupuncturist and the owner of Collective Health Center in Leesburg, Virginia. She loves diving into the medical literature in order to help patients get to the root causes of their troubling health conditions and getting them back with their health. She is grateful to all of the researchers who do the hard work that helps clinicians do better.
