Graves’ Disease causes hyperthyroidism, weight loss, anxiety & fatigue. Find out the causes of Graves’ Disease & treatments.
What is Graves’ Disease?
Graves’ Disease Diagnosis
When doctors diagnose this disease, they usually look at the patient’s’ blood test results. Graves’ disease patients usually have high levels of thyroxine (T4) and triiodothyronine (T3) and undetectable levels of thyroid stimulating hormone (TSH) .
When the diagnosis is uncertain, there are additional tests that measure the patient’s’ TSH receptor antibodies (TRAb) and radioactive iodine (RAI) uptake. Or, a thyroid ultrasound with Doppler is used .
Graves’ Disease Symptoms
Common symptoms include :
- Weight Loss
- Eye pain and redness
- Ophthalmopathy (eyeball swelling and protrusion)
- Dermopathy (skin disease)
- Difficult breathing
- Increased heart rate
- Thyroid enlargement
Meanwhile, women may have irregular periods, hair loss, or neck swelling .
Causes and Mechanisms
Immunoglobulins (IgG antibodies) bind to and activate the thyroid stimulating hormone (TSH) receptor on thyroid gland cells. This causes thyroid gland cell growth, which results in an enlarged thyroid and high thyroid hormone levels .
- Stressful life events
- Iodine exposure
- Recent childbirth
- A family history of Graves’
- Other autoimmune diseases
Women have a higher risk of getting the disease. Most Graves’ patients get it before 40 – 60 years old, but every age is susceptible .
Graves’ Disease and Other Health Issues
Graves’ Disease and Ophthalmopathy
One main symptom of Graves’ is ophthalmopathy, an eye disease. It causes the eye to protrude and the eyelids to retract and lag when opening or closing. T cells (white blood cells) in the body recognize an antigen (a molecule that causes an immune response) in the eyes and release cytokines into the tissue. This leads to swelling and eyeball protrusion .
Patients usually have a sandy sensation in their eyes, blurry vision, infrequent blinking, dry eyes, and irritation .
Graves’ Disease and Dermopathy
Another characteristic, physical change that Grave’s Disease causes is the development of dermopathy. Dermopathy is a skin condition that causes the skin to become red and thick, resembling that of an orange. Skin lesions also form .
Acropachy is a type of dermopathy. It is when the tissues in the hands and feet swell .
Graves’ Disease and Pregnancy
In pregnant women with Graves’ disease, the antibodies can cross the placenta and also cause thyroid dysfunction in the fetus .
Because Graves’ is an autoimmune disease, it can be problematic during the early stages of pregnancy. However, during pregnancy, the immune system is suppressed and Graves’ can improve .
If hyperthyroidism and Graves’ is unmanaged, it can cause problems such as :
Graves’ Disease and Cancer
Graves’ disease patients have a higher risk for cancer than healthy people. In a meta-analysis of 33 studies, Graves’ patients had double the risk of getting thyroid cancer .
Additionally, in a cohort study of 25,000 patients, the Graves’ patients had a higher risk of having head and neck, liver, breast, prostate, and thyroid cancer .
Graves’ Disease and Hashimoto’s Thyroiditis
Unlike Graves’, Hashimoto’s occurs when an antibody blocks TSH hormone activity and causes damage to the thyroid gland.
After discontinuing antithyroid treatment for 5 – 10 years, 15 – 20% of patients that recover from Graves’ can develop hypothyroidism due to Hashimoto’s. Although the exact cause is unknown, researchers think that antithyroid medication can contribute to abnormal thyroid hormone levels .
Graves’ Disease and Other Autoimmune Diseases
Graves’ disease is associated with a higher risk of other autoimmune diseases. In a study (cross-sectional) of 3200 UK thyroid patients, 9.6% of the Graves’ disease patients had another autoimmune disorder .
People with Grave’s can also have :
- Rheumatoid Arthritis
- Inflammatory Bowel Disease (IBD)
- Vitamin B12 deficiency anemia (not enough red blood cells)
- Celiac Disease
- Vitiligo (loss of skin color)
- Type 1 diabetes
Graves’ Disease and Myasthenia Gravis
Although Graves’ and myasthenia gravis are both autoimmune diseases, it is rare to have these two diseases at the same time. Both diseases may have the same mechanism involving Th17 cells .
Supplements that Decrease Thyroid Hormone Levels
There are many natural supplements you can take to lower your thyroid hormone levels. They include:
- Apigenin 
- Luteolin 
- Quercetin 
- Fisetin 
- Naringenin 
- Naringin 
- Myricetin 
- Kaempferol 
- Catechins 
- Flavonoids (Milk thistle, Citrus bioflavonoids, Resveratrol) 
- Lipoic acid 
- Tulsi 
- Thymus extract 
- Lemon balm 
- Aloe vera 
- Fulvic and humic acid 
- Biochanin A 
- Rutin 
- Ginseng 
AJBHT is a herbal remedy that contains 8 medicinal herbs that help aid thyroid function. These herbs include kudzu, Chinese skullcap, gypsum, platycodon, Angelica tenuissima, Chinese cimicifuga, fragrant angelica, and Chinese licorice .
In a study (clinical trial) of 22 Graves’ patients, AJBHT reduced T3 and T4 levels while it increased TSH .
Additionally, because of a lack of side effects, AJBHT is a good alternative to medication and anti-thyroid drugs that can cause other health problems .
1) Antithyroid Medications (Thionamides)
Propylthiouracil (PTU) and methimazole (MMI) are two antithyroid medications that help treat Graves’. They block the production of thyroid hormones. Doctors usually recommend antithyroid medication as the primary treatment for Graves’ disease .
However, since it mainly inhibits thyroid hormone production and does not address the cause of the disease, patients can experience a high rate of disease recurrence .
Patients take 15 – 30 mg of MMI once daily, and the dosage can be lowered to as little as 5 mg. Although it can cause liver and bile problems, it is more effective and has fewer side effects than PTU .
Meanwhile, patients usually take 50 – 150 mg of PTU 3 – 4 times daily. PTU can potentially cause hepatitis and liver failure .
While antithyroid medications are generally well-tolerated, their side effects also include stomach problems, muscle pain, and rashes. They might also cause agranulocytosis, or extremely low white blood cell count .
Thionamides in Combination with Supplements
Selenium helps with normal thyroid function, and selenium supplementation can enhance the effects of antithyroid medication. In a study (CT) of 41 Graves’ patients, the group that received selenium supplementation had lower T3 and T4 levels, as well as higher TSH levels than the control group .
A combination of MMI and a traditional Chinese medicine, Yingliu, may also improve MMI’s effects. Yingliu contains Astragalus and Anemarrhena roots and Prunella vulgaris .
In a study (RCT) of 92 Graves’ disease patients, the patients who also took Yingliu in addition to MMI had lower T3 and T4 levels and higher TSH levels than the patients who only took MMI antithyroid medication .
2) Potassium Iodide
Beta-blockers are drugs that help reduce high blood pressure or treat heart problems. Using beta-blockers can help rapidly relieve some hyperthyroid symptoms, such as increased heart rate. However, they have no effect on thyroid hormone levels .
Rituximab is an anticancer drug that may help reduce thyroid eye disease. In a study (CT) of 20 Graves’ patients, it helped prevent hyperthyroid relapse and reduced eye disease symptoms. However, due to its high cost, side effects, and low effectiveness, it is not a good treatment option .
Radioactive Iodine (RAI) Therapy
Radioactive Iodine (RAI) therapy uses radioactive iodine (I-131) and can either be used after antithyroid medication or as the initial treatment for Graves’ and hyperthyroidism. RAI treats hyperthyroidism by destroying enough thyroid tissue to lower thyroid hormone levels [31, 3].
Although RAI is relatively safe, pregnant women should not undergo RAI because it can damage the fetus. Additionally, RAI may increase the risk for heart problems, hypothyroidism (low thyroid hormone levels), and cancer .
Thyroid Removal Surgery
Doctors usually recommend removing the thyroid or parts of the thyroid (thyroidectomy) if the other treatments were unsuccessful, unsafe, or if the patient cannot undergo other treatments. Additionally, removing the thyroid can provide quick results in comparison to other therapies .
Pregnant women can undergo thyroid removal surgery to prevent damage to their fetus from antithyroid medication or RAI .
Patients who undergo thyroid removal surgery for Graves’ disease have a risk for bleeding and nerve injury. They are also at risk for hypothyroidism (low thyroid hormone levels) after the procedure [32, 25].
Other Potential Treatments
Although these new treatments are promising alternatives to the three main therapies, no human clinical trials are available.
Human Monoclonal Autoantibodies
Monoclonal antibodies (Mabs) are made in laboratories from human immune cells and can help detect and/or stop harmful antibodies. One Mab, 5C9 IgG, can block thyroid-stimulating antibodies. 5C9 may be able to prevent TSH activity during Graves’ disease .
Small Molecule Antagonists
Graves’ Disease and Genes/SNPs
A combination of environmental and genetic factors affect a person’s risk for Graves’ disease. If you have a close relative with Graves’, then you have a higher chance of getting the disease .
The HLA genes play an especially important role in the probability of getting Graves’. Although the exact genes are unknown, some variants that have a positive association with Graves’ disease risk include DRB1*03 (in Whites and Blacks) and DPB1 (in Asians) .
- rs2476601 (PTPN22)
- rs1883832 (CD40)
- rs231775 (CTLA4)
- rs3087243 (CTLA4)
- rs2268458 (TSHR)
- rs2239610 (TSHR)
- rs7528684 (FCRL3)
- rs3761959 (FCRL3)
- rs11264798 (FCRL3)
- rs10489678 (FCRL3)
- rs1368408 (SCGB3A2)
- rs41295061 (IL2RA)
Many patients comment that they were diagnosed a long time after showing symptoms of the disease. It is important that you see a doctor when you start exhibiting symptoms to ensure prompt treatment.
Their treatment experiences varied. Some people recover from the disease through RAI therapy. Meanwhile, others saw benefits from thyroid removal surgery or antithyroid medication.