Graves’ disease is an autoimmune condition that causes overactivity of the thyroid gland.  The resulting symptoms may include anxiety, heart palpitations, insomnia, accelerated transit time through the digestive system, weight loss, bulging and painful eyes (ophthalmopathy), goiter, and changes in the menstrual cycle or erectile dysfunction.  The symptoms may develop suddenly and can be very alarming.  To restore quality of life to those afflicted, there must be swift identification of risk factors, followed by treatment that addresses immune modulation and symptomatic relief.

Risk Factors

Genetics

Genetics is a key player in disease activity.  Genetic susceptibility can be vertically transmitted—passed from one generation to the next.  Unfortunately, such susceptibility may not be specific to one condition.  Having one autoimmune condition increases the risk of having another, implying an inherited dysregulation of the immune system as well as the condition itself.  Fortunately, genes are not static.  They can be turned on and off, driving disease activity up and down.   So the key to controlling autoimmunity lies in controlling gene expression.  By virtue, the next step should be to identify modifiable environmental factors that may impact disease activation and progression.

Sex

Women are five times more likely to develop Graves’ disease than men1, and if they get pregnant, the stakes are higher.  There are notable patterns around pregnancy.  It is common to see a heightening of symptoms in the first half of gestation, followed by a period of respite, and a resurgence post-partum2, indicating a strong relationship between hormones and disease activity.  To identify hormone imbalances, saliva testing is indicated.  However, if saliva testing is too expensive, hormones can be indirectly assessed by reviewing the menstrual cycle.  A healthy menstrual cycle is a good indication of hormone balance.  So what does a healthy menstrual cycle look like?

  • No premenstrual syndrome (PMS) i.e. mood changes, bloating, headaches, breast tenderness, fluid retention, food cravings, insomnia, acne, significant changes in digestion (constipation, diarrhea), significant fatigue, increased muscle and/or joint pain
  • Interval (number of days from day 1 of one period to day 1 of the next): 25-35 days
  • Duration (number of days menstruating, including spotting): 2-7 days
  • Flow volume: 10-80 mL per menstruation i.e. < 17 regular tampons or pads, 5-6 regular tampons or pads per day on the heaviest day(s)
  • No menstrual cramps or low back pain

If experiencing menstrual irregularities, speak to a Naturopathic Doctor about possible treatments.  Within 3-6 months of treatment, significant strides can often be made in balancing hormones.

Stress

Chronic or acute physical, mental, and emotional stress can activate Graves’ disease.  Stress is often perceived as outside our control, making it one of the hardest etiological factors to manage.  Mitigating stress often requires a critical appraisal of our lifestyle, taking inventory of what adds value and what diminishes our joy.  Replacing social conventions of success and worth with true happiness and purpose, will tip those scales and, ultimately, reduce stress.

Supplementation

The goals in treating Graves’ disease are to reduce thyroid hormone production, and to protect the tissues from overexposure to thyroid hormone.  Conventional medical treatments include radioactive iodine or anti-thyroid medications to block the production of hormones, and beta-blockers to reduce symptoms.  Naturopathic Medicine also has an important role to play in reducing risk factors, modulating the immune system, and addressing symptoms.  Botanical medicine, in particular, shows real promise.

Tripterygium wilfordii

Tripterygium wilfordii is a vine that is used commonly in Traditional Chinese Medicine for the treatment of autoimmune conditions, including rheumatoid arthritis, psoriasis, and Graves’ disease.  A 2019 meta-analysis showed that, when compared to conventional treatment alone, the addition of oral supplementation of Tripterygium wilfordii significantly reduced ocular symptoms in Graves’ disease.3

Lycopus

Lycopus is a species of plant in the mint family that is native to Europe, Asia, Australia, and North America.  To date, there are limited scientific studies on the use of this botanical for the treatment of Graves’ disease.  Lycopus, however, has been frequently cited anecdotally throughout history as an effective treatment for hyperthyroidism, particularly to reduce palpitations, insomnia, anxiety, and tremors.  Though this plant has not been studied in depth, one of its key constituents, rosmarinic acid, has.  The research on rosmarinic acid may elucidate the therapeutic benefits of Lycopus in the treatment of hyperthyroidism.

Rosmarinic acid elicits a multiplicity of actions in Graves’ disease.  To better understand its mechanisms of action, the physiology of the thyroid gland must first be understood.  When thyroid stimulating hormone (TSH) binds to the thyroid gland, it induces adenylate cyclase activity within the thyroid cells.  This results in increased production of thyroid hormone.  The way rosmarinic acid elicits its anti-thyroid effects is four-fold.  First, it inhibits Graves’ antibodies from binding to TSH receptors on the thyroid gland, preventing excessive downstream production of thyroid hormone.4,5  It also binds loosely to TSH preventing its interaction with the thyroid gland.6  Next, it blocks adenylate cyclase, reducing thyroid hormone output.7,8  Finally, rosmarinic acid has been shown to cause selective T-cell apoptosis in autoimmune conditions.  This means that it has the capacity to identify and eliminate just the overactive and dysregulated T-cells of the immune system, while simultaneously protecting the healthy naïve T-cells.  Ultimately, the end result is the restoration of immune balance.9,10

Due to the complexity of botanicals and their potential interactions, the aforementioned herbal medicines should not be taken unless under the guidance of a trained healthcare practitioner, like a Naturopathic Doctor.

Conclusion

Graves’ disease may effect 1-2% of the population, but a diagnosis does not have to equate with chronic disease and debility.  Though the etiology of this condition is complex, successful treatment relies on simple principles: employ a global assessment of health to identify risk factors, and treat the body holistically to modulate the immune system and maximize disease management.

References

  1. Kahaly, J. (2011). Graves’ disease: diagnostic and therapeutic challenges (multimedia activity). American Journal of Medicine, 124(6), S2-3. https://doi: 10.1016/j.amjmed.2011.03.001.
  2. Lucile Packard Children’s Hospital Stanford (n.d.). Graves Disease in Pregnancy. https://www.stanfordchildrens.org/en/topic/default?id=graves-disease-in-pregnancy-90-P02460
  3. Liu, X, et al. (2019). Efficacy and safety of tripterygium glycosides for Graves ophthalmopathy: a systematic review and meta-analysis. Medicine (Baltimore), 98(50): e18242. https://doi: 10.1097/MD.0000000000018242.
  4. Santini F, Vitti P, & Ceccarini G. (2003). In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest, 26(10): 950–5. https://doi: 10.1007/BF03348190.
  5. Auf’mkolk, M, et al. (1985). Extracts and auto-oxidized constituents of certain plants inhibit the receptor-binding and the biological activity of Graves’ immunoglobulins. Endocrinology, 116(5): 1687–93. https:// doi: 10.1210/endo-116-5-1687.
  6. Auf’mkolk, M, et al. (1985). The active principles of plant extracts with antithyrotropic activity: Oxidation products of derivatives of 3,4-dihydroxycinnamic acid. Endocrinology, 116(5): 1677–86. https://doi: 10.1210/endo-116-5-1677.
  7. Auf’mkolk, M, et al. (1984). Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology, 115(2):527–34. https://doi: 10.1210/endo-115-2-527.
  8. Kleemann, S, et al. (1990). Rosmarinic acid and freeze-dried extract (FDE) of Lycopus virginicus are able to inhibit forskolin-induced activation of adenylate cyclase in cultured rat thyroid cells. Plant-Med, 56(6): 683.
  9. Yun-Gyoung, H, et al. (2007). Rosmarinic acid induces apoptosis of activated T cells from rheumatoid arthritis patients via mitochondrial pathway. J of Clin Immun, 27:36-45. https:// doi: 10.1007/s10875-006-9057-8.
  10. Habza-Kowalska E, et al. (2019). Thyroid peroxidase activity is inhibited by phenolic compounds—impact of interaction. Molecules, 24(15): 2766. https:// doi: 10.3390/molecules24152766.