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First described by Robert Graves in 1835, Graves' disease (GD) is an autoimmune disease that arises as a consequence of the body producing antibodies against the thyroid (thyroid stimulating immunoglobulins) that result in excess thyroid hormone production. GD is the most common diagnosis underlying the development of hyperthyroidism in patients in North America and is the most common autoimmune disease in the United States and Canada, with the incidence in women ~ 0.5 cases per 1000 individuals. The precipitating event for the production of the antibodies and the development of the disease remains poorly understood. The antibodies stimulate the TSH receptor on the thyroid gland, resulting in enlargement of the thyroid and excess thyroid hormone synthesis and secretion. Patients with Graves' thyroid disease are also at increased risk for the development of Graves' eye disease, also known as thyroid ophthalmopathy that becomes apparent in about 50% of patients with GD of the thyroid. The eye disease and the thyroid disease may be viewed as 2 separate diseases, as one does not invariably accompany the other. Furthermore, treatment of the hyperthyroid state with drugs does not usually influence the course of the eye disease, which can run an independent course, even though the thyroid disease invariably improves with all treatment options. Nevertheless, patients with severe Graves' eye disease appear to be less likely to experience permanent remissions of their hyperthyroidism after treatment with medications alone as described in Patients with severe Graves' ophthalmopathy have a higher risk of relapsing hyperthyroidism and are unlikely to remain in remission. Clin Endocrinol (Oxf). 2007 Oct;67(4):607-12.
Patients with GD may also develop thickening of the skin in the legs, particularly around the shins, a condition known as thyroid dermopathy, and rarely if the swelling of the legs is significant, the condition may be referred to as pretibial myxedema. This latter condition is very uncommon.
Although stress is often noted prior to or coincident with the development of GD, it is not possible to state with complete certainty that there is a scientific link between stress and the development of GD.
Patients that exhibit characteristic features of GD, such as a symmetrically enlarged smooth thyroid, with features of eye disease or dermopathy usually do not need additional investigations to make the diagnosis. Occasionally, patients may have a small or normal thyroid and no other features of GD. In this instance, an iodine uptake and possibly a scan may be helpful to differentiate GD from other causes of hyperthyroidism.
About 10-20% of all patients with GD may have a spontaneous remission of their disease within the first year of diagnosis, however the remission is frequently not permanent and the disease commonly recurs. To review the Treatment Options, return to Hyperthyroidism or see the sections on Drugs or Radioactive iodine.
For a comprehensive review of Graves' disease, see The New England Journal of Medicine -- October 26, 2000 -- Vol. 343, No. 17 Medical Progress: Graves' Disease 1236-1248.
How do I decide what treatment option to pursue; none of the options sounds perfect?
The choice of surgery versus medications versus radioactive iodine is an individual one, and may be influenced by the size of the thyroid and severity of the hyperthyroidism, patient and physician preferences, and co-existing medical conditions. Both radioactive iodine and surgery are associated with higher rates of definitive treatment, due to their destruction and removal of thyroid tissue. Some data from Sweden on the relative rates of disease remission after different approaches is found here The long-term outcome of treatment for Graves' hyperthyroidism Thyroid. 2019 Sep 4. doi: 10.1089/thy.2019.0085
When is surgery indicated as a treatment for Graves' disease?
In many centers, particularly in Europe, surgery is a common first line treatment for Graves' disease. In North America, radioactive iodine and medications tend to be used more than surgery. Patients who are pregnant and have medication allergies, patients with extremely large thyroid glands, and patients with one or more thyroid nodules and Graves' disease often represent reasonable surgical candidates. The risk of thyroid cancer developing in a cold nodule in Graves' disease is ~ the same risk as in patients without Graves' disease, namely about 15%. To review a study of this issue, see Multicentre study of thyroid nodules in patients with Graves' disease. Br J Surg. 2000 Aug;87(8):1111-3.
Can I have part of my thyroid removed by laparoscopy and avoid a scar?
The use of laparascopy in partial thyroidectomy is still considered experimental, but under investigation in some centers. It may be possible to consider this type of option in the future, if experience with a larger number of patients proves satisfactory. For an assessment of this option, see Endoscopic subtotal thyroidectomy for patients with Graves' disease. Surg Today. 2001;31(1):1-4.
I feel fine right now but everyone says I have to be treated or I will become ill. At what point must I start treatment?
It is not unusual for the diagnosis of Graves' disease to be made early at a point when blood tests or iodine uptake studies point to an abnormality, yet few or no clinical symptoms may be present. It seems reasonable to have a discussion about the ideal time to institute therapy, with your physician, taking into consideration ancillary factors such as any potential planned pregnancies in the future etc. In many instances, it may not be absolutely necessary to initiate treatment unless symptoms are present, but careful monitoring should be initiated.
If I choose medicines, how long do I need to take the medicines for?
Anti-thyroid medicines such as methimazole and propylthiouracil are generally takne for at least 6 months, depending on the size of the thyroid, clinical characteristics, and the response to therapy. Some studies show that longer courses of treatment are more likely to be associated with a higher rate of remission Benefits of Long-Term Continuation of Low-Dose Methimazole Therapy in the Prevention of Recurrent Hyperthyroidism in Graves' Hyperthyroid Patients: A Randomized Prospective Controlled Study Int J Endocrinol. 2022 Oct 11;2022:1705740
Also see https://mythyroid.com/medicationshyper.html