How Effective Are The Three Treatments For Graves’ Disease?

Graves’ disease is an autoimmune disorder that targets the thyroid gland. It is the most common cause of hyperthyroidism, a condition characterized by excessive amounts of thyroid hormones circulating throughout the body.

Graves’ disease is a lifelong condition that often requires long-term treatment. However, management of the disease and its symptoms is achievable. And, fortunately, remission is possible too.

What determines whether Graves’ disease has been cured?

The definition of ‘cured’ concerning Graves’ disease can vary across experts and studies. 

Some definitions include:¹

• Abolishing an excess thyroid-hormone state, achievable with the three most common forms of Graves’ disease treatment (antithyroid medications, radioiodine treatment, and thyroidectomy surgery)

• The disappearance of thyroid antibodies in the blood, although this is unusual

• Normal and stable thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (T3) for at least one year, in the absence of antithyroid medication. This is sometimes known as permanent remission.² Surgery and radioactive iodine are less likely to lead to this state because they cause hypothyroidism, where the thyroid produces an abnormally low amount of thyroid hormones.

• Becoming euthyroid or hypothyroid after 12 months

Since thyroid antibodies are the underlying cause of Graves’ disease, the disappearance of these antibodies gives patients the highest chance of reaching complete remission. However, this is difficult to achieve.

Remission

Because of the different definitions of a ‘cure’ with respect to Graves’ disease, patients who make significant improvements are often considered to be in remission rather than fully cured.

Remission is also thought to be a more accurate term because even if your Graves’ disease goes away, it can come back; this is called a ‘relapse.’ The natural course of Graves’ disease often involves cycles of relapse and remission.

A small percentage of people with Graves’ disease – less than 10% – remain in a constant state of hyperthyroidism.¹ This means that they may not be able to reach remission, although they can still control their condition with treatment.

Treatments and cures

Whether or not a certain treatment can ‘cure’ Graves’ disease depends on the aim of that treatment. Generally, treatment aims to do one of the following:

• Stop the overproduction of thyroid hormones

• Stop the effects of increased thyroid hormone levels on the body

• Render the patient hypothyroid

Left untreated, Graves’ disease does not go away on its own. It often worsens and can lead to serious complications such as:

• Eye disease

• Heart problems

• Skin problems

• Dangerously high thyroid levels that may cause a ‘thyroid storm.’

Beta blockers are not considered a cure for Graves’ disease. This is because they only treat the symptoms of hyperthyroidism. They do not stop the thyroid gland from producing thyroid hormones or decrease thyroid-stimulating antibodies.

Antithyroid medications

The antithyroid medications currently available in the US include propylthiouracil and methimazole.

These medications are also generally the treatment of choice in Europe and Japan, despite a relatively high relapse rate compared to other treatments such as total thyroidectomy and radioiodine therapy.¹

Propylthiouracil or methimazole is often the first treatment choice because both offer a better chance of preserving normal thyroid function (i.e., avoiding hypothyroidism³), and because radioiodine therapy, a common alternative, is associated with worsening Graves’ ophthalmopathy.

What is the aim?

The aim is to enable patients with Graves' disease to enter into remission and resume normal thyroid function without needing to continue taking the medication for longer than necessary.

Can it cure Graves’ disease?

A single course of antithyroid drugs leads to remission in about 50% of patients after 12 to 18 months.¹

A third of patients remain in permanent remission.¹ However, some of these patients still have TSH receptor antibodies, so some experts may not consider them fully cured.

Some studies suggest a link between the duration of treatment with antithyroid drugs and the duration of remission.²

One study showed that females were more likely to experience remission,⁴ where remission is defined by the maintenance of normal thyroid hormone levels one year after stopping medication. 

Failure to cure Graves’ disease

Some studies have shown that after discontinuation of antithyroid medication, around half of people will experience a recurrence of Graves’ disease hyperthyroidism within four years.¹

Some factors appear to be associated (however minor) with lower remission rates and/or a shorter duration of remission. You may be at a slightly elevated risk if you:

• are male 

• are younger than 40 years old

• smoke cigarettes 

• have severe hyperthyroidism

• have a large goiter

• have Graves’ ophthalmopathy

• have had Graves’ disease for more than six months⁵

• have high TSH receptor antibody levels at the end of treatment (known as ‘persistent hyperthyroidism’). 

• have low TSH levels during treatment, at the end of treatment, and three months after treatment

• have experienced a previous relapse⁵

• undertook a shorter duration of treatment²

In instances where remission is less probable, a more permanent ‘definitive treatment,’ which may include either a total thyroidectomy or radioiodine therapy, could be more successful.²

In most cases, definitive treatments, rather than a second course of antithyroid drugs, are encouraged after a relapse. On the other hand, some studies suggest that a longer-term low dose can still help patients control hyperthyroidism.⁶

It is also more common to experience a late-onset relapse if antithyroid medications are used without other treatments.

Relapse rates decrease over time, with the majority occurring within one year of treatment ceasing.⁷

Radioiodine therapy

What is the aim?

In the US, radioiodine therapy is becoming the treatment of choice for Graves’ disease.⁸ It involves shrinking or killing overactive thyroid cells. 

It is difficult to predict the outcome or to suggest a dose that can simultaneously cure hyperthyroidism, whilst also preventing the development of hypothyroidism as a consequence of treatment. Hypothyroidism is the opposite of hyperthyroidism – it occurs when the thyroid doesn't produce enough thyroid hormones. 

The most viable aim of radioiodine therapy is to control and cure hyperthyroidism by causing the patient to become permanently hypothyroid. Radioiodine therapy is thus considered a ‘definitive therapy.’⁴ Hyperthyroidism is cured because the cells that produce thyroid hormones are destroyed. 

Can it cure Graves’ disease?

Elimination of Graves’ disease is possible, although the number of doses required may vary. However, this cure most often comes at the expense of developing hypothyroidism.¹ It is thought that the thyroid tissue that is damaged due to the radioiodine therapy may be unable to maintain its normal hormonal function.⁸

Normal thyroid function can resolve within six to eight weeks in 50%–75% of patients.⁵

Failure to cure Graves’ disease

A study showed that one year after the first dose of radioiodine therapy, 17% of participants were still hyperthyroid, 77% were hypothyroid, and just 6% were euthyroid (thyroid gland is functioning normally). However, after a second and third dose was administered, at the 80-month check, the percentage of participants who were still hyperthyroid was significantly reduced.¹

People were more likely to remain hyperthyroid or have a failure with radioiodine therapy after their first dose if they had:

• higher free thyroxine (FT4) at the time of initial diagnosis

• higher thyroid-stimulating hormone receptor antibodies (TSHRAb) before beginning treatment 

• a thyroid gland larger than 50 cubic centimeters⁸

Sometimes, Graves’ ophthalmopathy, a condition associated with Graves’ disease, can develop or be worse after radioiodine therapy. This is thought to happen because TSI antibodies are still present in over half of patients following radioiodine therapy, and their numbers can even increase in the six months following treatment.¹

Surgery (thyroidectomy) 

What is the aim?

A thyroidectomy involves the full or partial removal of the thyroid gland. Depending on how much of the thyroid is removed, this procedure can result in the elimination of thyroid hormones, which is why some consider it a ‘cure’ for hyperthyroidism.

Like radioiodine treatment, a thyroidectomy is considered to be a ‘definitive therapy,’ because it removes hyperthyroidism by causing permanent hypothyroidism.⁴

Can it cure Graves’ disease?

Studies have shown that a total thyroidectomy has the highest success rate of all treatments for controlling Graves’ hyperthyroidism and offers a nearly 0% risk of recurrence.¹ With a subtotal thyroidectomy, there is an 8% chance of either persistence or recurrence of hyperthyroidism five years after the surgery. 

The concentration of thyroid-stimulating immunoglobulins (TSI) in the blood decreases during the nine months after surgery; however three months post-surgery, about 18% of patients still have TSIs.¹

Failure to cure Graves’ disease

A subtotal thyroidectomy is a less effective ‘cure’ than a total one, and fewer people who undergo this treatment remain in remission (compared to those who undergo a total thyroidectomy). 

One study showed that, six years after surgery, about one-third of subtotal thyroidectomy participants still had persistent or recurrent Graves’ hyperthyroidism. Of the remaining participants, 20% were euthyroid and the rest were hypothyroid.¹

This suggests that undertaking a subtotal thyroidectomy should not be done with the intent of reaching true remission and becoming euthyroid. 

Special circumstances 

Sometimes pregnant women with Graves’ disease go into remission during the final trimester of their pregnancy, when the thyroid hormone thyroxine (T4) levels fall.⁴ This is likely because the immune system is less active during this time.

However, postpartum Graves’ disease and a rebound of symptoms occur in about 10% of women.

Which treatment is most likely to cure Graves’ disease?

It is difficult to know which treatment is most likely to cure Graves’ disease or offer remission because different treatments are suitable for different people. There are pros and cons to each option, and patients will need to take many different factors into account.

For example, antithyroid medications are less likely to fully ‘cure’ Graves’ disease, as they are not definitive treatments. On the other hand, definitive treatments such as surgery and radioiodine therapy have a large risk of inducing hypothyroidism.

Furthermore, the three common treatments cannot guarantee the curing of Graves’ disease, as thyroid antibodies can remain in the blood, allowing the underlying cause of Graves’ disease to persist.

If you want to undertake treatment for Graves’ disease and give yourself the best chance of remission, it is important to consult with your doctor. They will be able to suggest the best treatment for you based on your medical history and other personal factors.

Can you cure Graves’ disease or increase your chance of remission naturally?

Natural treatments will not cure Graves’ disease, and they should not be used as a replacement for the evidence-based treatments that either directly suppress thyroid function or stop the effects of hyperthyroidism on the body.

However, some natural treatments can help support you and lessen your symptoms while you are undertaking conventional treatments. Three science-backed examples are:

Supplementation with selenium

Supplementing with selenium twice a day for two months can slow down the progression of mild Graves’ ophthalmopathy, likely by acting as an antioxidant.⁹

This is important because Graves’ disease and ophthalmopathy are associated with oxidative stress (an imbalance between the production of damaging molecules called ‘free radicals’ and antioxidants, which can remove them).¹⁰

Freeze-dried extracts of some plants

These extracts also have components that could interact with the antithyroid antibodies in Graves’ disease, preventing them from binding to the TSH receptor and activating the thyroid.¹¹

Vitamin D supplements

Vitamin D deficiency is associated with higher levels of thyroid antibodies and a higher chance of relapse.¹³ Vitamin D supplements could decrease thyroid antibodies¹² and possibly reduce the chance of relapse after treatment.

The lowdown 

The treatments used to treat Graves’ disease, such as antithyroid medication, radioactive iodine therapy, and thyroidectomy surgery, all have the potential to restore normal thyroid function.

These treatments enable many patients with Graves’ disease to reach remission. However, remission is not always permanent, and relapse is possible. In the case of definitive treatments, the onset of hypothyroidism can require regular, lifelong checkups and the prolonged use of new medications. Finally, in most cases, current treatments do not address the underlying cause of circulating antithyroid antibodies.