Graves’ disease is an autoimmune thyroid condition that affects approximately 3% of women and 0.5% of men at some point in their lifetime.1 This disease was first observed by Irish physician Robert Graves in 1835.
It causes hyperthyroidism as a result of the overproduction of antibodies called ‘thyroid-stimulating immunoglobulins’, which stimulate an overproduction of thyroid hormones.
As the thyroid gland and its hormones are closely tied to the endocrine system, metabolism, and the sympathetic nervous system, this disorder can have serious effects on multiple body organs and functions.
People with Graves’ disease may also experience Graves’ orbitopathy (GO), a condition characterized by swelling of tissues behind and around the eye, causing the eyes to bulge.
There are three main treatment options available for Graves’ disease.²
Two options – radioactive iodine (RAI) therapy and the partial or full surgical removal of the thyroid gland – aim to put the patient into a state of hypothyroidism, which can then be managed for life with the help of the drug levothyroxine.³
The third option – treatment with antithyroid drugs (ATDs) – has the goal of achieving euthyroidism, in which the thyroid functions normally.
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Eyes (Graves’ orbitopathy – GO)
Infection and irritation from exposure to pollutants
Sensitivity to light
Loss of vision, in severe cases
Central nervous system
Intolerance to heat
Shortness of breath
Low sex drive
Growth of breast tissue
Subfertility, or delay in conceiving⁴
Dermopathy – pitting edema (pretibial), elephantiasis
Enlarged, diffuse goiter
Antithyroid drugs (ATDs)
This thionamide class of drugs comprises methimazole and propylthiouracil, which are designed to stop the creation of new thyroid hormones.
Methimazole is the drug in this class most commonly used to treat Graves’ disease. Propylthiouracil is used less frequently, due to liver damage risks, and tends to be used if methimazole is not tolerated, or the patient is in the first trimester of pregnancy.
ATDs are uniquely able to normalize the TSHR antibodies (also called TRAb) over time, which could be why remission is possible after long-term ATD therapy.¹
ATDs are usually given for 12–18 months to observe if long-term euthyroidism is achievable. They are also used as a pre-treatment before RAI and surgery.
Radioactive iodine therapy (RAI)
RAI prompts radioactive iodine to be incorporated into thyroid hormones. Once there, it releases beta particles which are ionized and cause damage to the thyroid follicular cells – the main cells of the thyroid.
Eventually, the thyroid gland will be damaged.
The purpose of RAI is to place the patient into a hypothyroid state, in which the thyroid is underactive, requiring controlled medical management for life. In most patients, this is achieved two to three months after treatment, with only a single dose of RAI being necessary.¹
Surgery used to be a first-line, definitive treatment for Graves’ disease. However, after the development of RAI and ATDs, it has taken a backseat. Fewer than 1% of physicians now recommend surgery as a first option.¹
Symptoms that may prompt thyroid surgery include:
Very large goiters compressing neighbouring parts of the body
Suspicious thyroid nodules
Sometimes women of childbearing age will select the surgical option for treatment, as there are some concerns regarding the use of RAI when pregnancy is imminent.
Generally, the notion of a ‘cure’ in medicine is guided by the term restitutio ad integrum³ – Latin for ‘complete restoration to health.’
In the context of Graves’ disease and hyperthyroidism, that would mean returning the patient to a stable and long-term euthyroid state (without the use of ongoing medication), in which the patient’s circulating TSH, triiodothyronine (T3), and thyroxine (T4) levels are normal.³
As we have already seen, most patients enter a hypothyroid state within two to three months after a single dose of RAI. However, 5%–15% of patients require a second dose.¹
RAI has been shown to worsen Graves’ orbitopathy by 3.2–5.8 times, presumably because, even though thyroid hormone levels fall, the TSHR antibody still remains after treatment.⁵ This can be prevented in part by taking steroids as prescribed by a physician.
However, if GO is severe, RAI is not an appropriate treatment option.
Surgery as the main definitive treatment
Surgery, where a total or near-total thyroidectomy is performed, is the main definitive treatment for Graves’ disease in the US. This has the greatest efficacy of all the treatment options with a success rate of 100%.⁵
However, there are some risks associated with surgery, including:
Laryngeal nerve palsy preceding vocal cord paralysis (>1%)¹
Transient or permanent hypoparathyroidism causing hypocalcemia (4%)¹
Hematoma of the neck (2.8%)⁵
General risks associated with anesthesia
Antithyroid drugs and remission
An advantage of antithyroid drugs is that long-term hypothyroidism is less likely compared to the other options. However, a disadvantage is that long-term success is also less likely, compared to RAI and surgery, which are considered definitive.⁵
ATDs are usually most appropriate for patients who have only mild disease, a small goiter, are female, or have few to no circulating TSHR antibodies.
Remission is categorized as being euthyroid 12 months after ATD treatment has ceased. Remission rates vary from study to study:⁵
In the US, a 20%–30% remission rate has been reported after 12–18 months, although one study reports a 52% remission rate
In Europe, a 50%–60% remission rate is reported after five years post-treatment
In Japan, the post-treatment remission rate is 68%
Going by the aforementioned definition of ‘cure,’ where symptoms must be normalized without medical control, a cure for Graves’ disease is not guaranteed, and it is not truly possible with RAI and surgery.³
This is because these treatments work to place the patient into a hypothyroid state where little to no thyroid hormone is naturally produced.
These treatments require compensatory action – i.e., taking levothyroxine for life. This is still a stable outcome, however, and most patients see their symptoms largely resolved and can return to a good quality of life.
Treatment with ATDs has the goal of achieving euthyroidism, where thyroid hormones are naturally produced in a controlled way. As we have stated, this is achieved in approximately 50%–70% of patients.⁵
For the remaining 30%–50% of patients, symptoms and the need for medication may still persist.
Graves’ disease is a complicated autoimmune condition where treatment requires maintaining a delicate balance of thyroid hormone concentration. The thyroid, and its production of thyroid hormone, must be under control, but other medications often have to be administered so that normal thyroid levels are achieved.
A cure is not achievable via all treatment options. Surgery and RAI can stabilize thyroid levels, but they require patients to take medication for the rest of their lives. The only treatment that may prompt true euthyroidism (in approximately 50%–70% of patients) is ATDs.
Speak to your physician about the risks and benefits of each type of treatment to determine the best option for you.