How To Diagnose Graves’ Disease

Grave’s Disease is a chronic autoimmune disorder that causes hyperthyroidism, a condition characterized by an overproduction of thyroid hormones and an enlarged thyroid gland. 

Getting an accurate diagnosis for Graves’ Disease is essential, as doing so will help prevent long-term complications and allow for the most effective treatments to be provided. 

For those who present with Graves’-specific symptoms, diagnosis is generally straightforward. For some, a diagnosis can be made after a couple of visits to the doctor and a blood test. 

However, others may need to undergo numerous tests to rule out other conditions. 

Getting a diagnosis: When to seek medical advice?

Since thyroid hormones affect many functions of the body, the symptoms of Graves’ Disease are wide-ranging. 

Some of the general hyperthyroidism symptoms experienced by people with Graves’ Disease include: 

• Anxiety or irritability 

• A tremor in the hands

• Weight loss

• Goiter (an enlarged thyroid gland)

• Changes to the menstrual cycle 

• Fatigue

• Low sex drive

• Frequent bowel movements

• A rapid and irregular heartbeat

• Sleep disturbance.

Graves’ Disease can also cause two conditions that come with their specific symptoms. These are:

• Graves’ Ophthalmopathy: an eye condition that causes vision loss, as well as bulging, itchy, and/or swollen eyes 

• Graves’ Dermopathy¹: a skin condition that causes thickened, red, and swollen skin on the shins and top of the feet. 

If you are experiencing any general or specific symptoms, it is important to see your doctor for an assessment. 

What type of doctors are involved in the diagnosis of Graves’ Disease?

• Your family doctor, who can carry out a physical examination, talk through your medical and family history and refer you for testing.

• An endocrinologist (a doctor who specializes in diseases that affect hormones).

• A radiologist (a specialist who reviews and reports on the results of imaging).

How is Graves’ Disease diagnosed? 

Graves’ Disease is usually easy to diagnose, especially if the symptoms of Graves’ Ophthalmopathy and/or Graves’ Dermopathy are visible. However, for some people, such as the elderly,² the disease can present in different ways.

The first step of diagnosing Graves’ Disease is to diagnose hyperthyroidism. Once this has been confirmed, the underlying cause of hyperthyroidism can be uncovered.

Graves’ Disease is the most common cause of hyperthyroidism. However, there are many other causes that prompt similar signs and symptoms. 

This means you may need to undergo several diagnostic tests in order to rule out other causes of hyperthyroidism and related conditions, such as:

• A tumor in the thyroid or pituitary gland

• Painless thyroiditis

• Plummer’s Disease

• Excess dietary iodine 

• Side effects of certain medications.

Physical examination

The first step towards getting a diagnosis is to see your family doctor. 

They will discuss your family history of hyperthyroidism and/or Graves’ Disease with you, as family history is a strong risk factor³ for developing Graves’. Your doctor will also discuss your personal medical history and current symptoms, and they ask you questions such as:

• How long have you had symptoms?

• How often do you experience symptoms?

• Are you taking any new medications?

• What symptoms do you have (including common hyperthyroidism symptoms and Graves’-specific ophthalmopathy and dermopathy)?

Your doctor will also carry out a physical examination where they will: 

• Feel your thyroid gland for evidence of goiter, which is caused by hyperthyroidism (in Graves’ Disease, the whole gland appears enlarged).

• Take your pulse.

• Check your eyes for irritation or bulging.

Diagnostic tests

Once your doctor has completed an examination and believes a hyperthyroidism condition such as Graves’ Disease is likely, they will refer you for further tests. 

These could include:

Thyroid hormone blood tests

These blood tests are important for confirming general hyperthyroidism. 

Thyroid Stimulating Hormone (TSH) 

TSH is produced by the pituitary gland. It stimulates the thyroid gland to produce thyroid hormones.

Normal values of TSH range from 0.5 - 4.0 mU/L.³ Lower values are indicative of hyperthyroidism, as is the case with Graves’ Disease. 

If TSH values are abnormal, two more hormones can then be measured:

Triiodothyronine (T3) 

T3 is a thyroid hormone that is produced by the thyroid gland. It is responsible for many processes in the body, from growth and development to metabolism to the regulation of body temperature.  

The T3 that circulates in the blood is called “free T3.” Normal values of free T3 range from 2.3 - 4.2 pg/mL.³ In hyperthyroidism, including in Graves’ Disease, levels of T3 are higher. 

Thyroxine (T4) 

T4 is another thyroid hormone produced in the thyroid gland. Like T3, it is responsible for many physiological processes throughout the body. 

Normal values of free T4 range from  0.8 - 1.8 ng/d.³ Again, as with T3, higher levels of T4 are indicative of hyperthyroidism. 

Based on the results from these tests alone, it can be difficult to differentiate Graves’ Disease from other causes of hyperthyroidism. A free T3/T4 ratio that is greater than 0.3 SI² unit could be indicative of Graves’ Disease. 

However, it is also possible for people with Graves’ Disease to have subclinical hyperthyroidism,⁴ where TSH levels are low but T3 and T4 are still within their normal range. 

This is why additional diagnostic tests are important.

Anti-thyroid antibody tests 

Graves’ Disease is an autoimmune condition that is distinguished by anti-thyroid autoantibodies, which are proteins that are produced as part of our immune response.  

In a normal immune response, foreign proteins called antigens stimulate the production of antibodies. These antibodies recognize, bind to, and remove the antigens from the body, preventing disease or toxicity. 

However, in autoimmune conditions, autoantibodies are produced. These fight against the body’s healthy proteins, which are incorrectly perceived as being foreign antigens. This occurs in Graves’ Disease, where anti-thyroid autoantibodies are produced to fight against proteins in the cells of the thyroid gland. 

The important anti-thyroid antibodies in Graves’ Disease are:

Thyroid-stimulating immunoglobulin (TSI) 

TSI is one of the thyrotropin receptor autoantibodies (TRAb). It is detected in 90% of people⁴ with Graves’ Disease. 

TSI binds to and stimulates the thyroid hormone receptor (TSHR). It mimics TSH and causes the thyroid gland to become more active, leading to excessive production of thyroid hormones T3 and T4 and enlargement of the thyroid gland. 

This antibody is measured through a blood test. The normal range of TSI is less than 130%.³ 

As well as being a diagnostic tool for Graves’ Disease, TSI is useful for assessing:

• How likely someone with Graves’ Disease is to have a relapse after treatment.

• The risk of neonatal Graves’ Disease in pregnant women.

TSI can also contribute to the symptoms associated with Graves’ Ophthalmopathy and Graves’ Dermopathy. 

Anti-thyroglobulin antibody (TgAb) 

TgAb is an antibody that fights thyroglobulin, a protein made by the thyroid gland which helps it to produce thyroid hormones. It is detected in around 50% of people with Graves’ Disease.⁵ 

It is measured through a blood test. 

Anti-thyroid peroxidase antibody (TPOAb)

TPOAb is an antibody that fights against thyroid peroxidase, an enzyme that is made by the thyroid gland to help produce thyroid hormones. It is detected in more than 95% of people⁵ with Graves’ Disease and is measured through a blood test. 

These autoantibodies are usually not detected in people with hyperthyroidism conditions that are unrelated to autoimmunity. 

However, it is important to keep in mind that these antibody tests, TPOAb and TgAb in particular, are not always the most reliable for diagnosing Graves’ Disease. This is because the antibodies can be detected in other autoimmune conditions, such as Hashimoto’s Disease or Type I Diabetes. Occasionally, these antibodies are also detected in the general population. 

Scans and imaging tests 

Radioactive iodine uptake test 

The radioactive iodine uptake test shows how well the thyroid is functioning. This is done by determining the rate at which the thyroid absorbs iodine. Iodine is a mineral that is used by the thyroid to produce thyroid hormones. 

The test involves ingesting radioactive iodine orally or through an intravenous line, where it is delivered through a small tube into your vein. Once it is in your system, a device called a gamma probe will be placed near the thyroid gland on your neck. 

Normally, six hours after ingestion of iodine, results range from 3% to 16%⁶ (percentage of Iodine uptake). At 24 hours post-ingestion, normal results range from 8% to 25%. In Graves Disease, the thyroid takes up too much iodine when antibodies bind to the TSH receptor, so results will show a higher level of radioactivity. 

The radioactive iodine uptake test is not recommended for pregnant or breastfeeding women, because exposure to radioactive material can be harmful to the fetus or baby. Additionally, you should alert your doctor if you have diarrhea, as this can decrease the absorption of radioactive iodine, making the test less accurate.

This test does require some preparation. For a week before the test, you will need to avoid food and supplements that either have iodine in them or that increase the amount of iodine absorbed by the thyroid. 

Moreover, the radioactive iodine uptake test needs to be combined with other types of testing, because a high uptake can be linked to other hypothyroidism conditions such as a toxic thyroid nodule. 

Thyroid ultrasound

Ultrasounds use sound waves to generate pictures of internal body structures, such as the thyroid gland. The resulting picture can then be analyzed to determine how enlarged the thyroid gland is. For pregnant women, this test is safer than the radioactive iodine uptake test. 

Ultrasounds are easy, quick, and non-invasive tests that don’t require any preparation on your behalf. 

Doppler ultrasound test

A Doppler ultrasound is similar to the ordinary ultrasound, where sound waves are used to generate an image of the internal body structures. 

However, a doppler ultrasound measures sound waves that are reflected from moving objects inside the body, such as red blood cells. This is then used to visualize the amount of blood that is flowing through blood vessels. 

In Graves’ disease, there is an increased flow of blood inside the thyroid gland. This is known as “thyroid inferno,⁷” where there are several small areas of increased flow, spread throughout the entire thyroid gland. 

This is a useful diagnostic tool because other types of thyroid problems can cause reduced blood flow through the thyroid gland. 

Doppler ultrasounds are not suitable for pregnant or breastfeeding women. This is because, unlike ordinary ultrasounds, Doppler ultrasounds have a higher risk of thermal damage to the fetal tissue. 

Other imaging tests

Imaging tests such as CT and MRI scans are useful for ruling out other causes of hyperthyroidism, such as thyroid tumors. 

They can also be used to examine eye muscles if you have eye swelling, which can be caused by Graves’ Ophthalmopathy, a complication of Graves’ Disease. Imaging tests can also help to differentiate Graves’ Ophthalmopathy from other eye diseases. 

Finally, these tests can help distinguish the early inflammatory stage of Graves’ from the inactive stage. 

Thyroid isotope scan

A thyroid isotope scan is an imaging test that uses radioactive iodine. It is often performed at the same time as a radioactive iodine uptake test. 

This scan can show: 

• The distribution of iodine in the thyroid gland.

• The size, shape, and position of the thyroid gland. 

• Whether there are thyroid nodules that produce excessive thyroid hormones (these areas will light up more).

In Graves’ Disease, iodine is spread consistently through the whole thyroid gland. However, in some other conditions, iodine will be concentrated in one specific area of the gland. 

Thyroid isotope scans are not recommended for pregnant or breastfeeding women due to the risk of fetal radiation exposure.

Based on these tests, diagnostic criteria⁸ for Graves’ Disease have been suggested. These state that a person with too much thyroid hormone in the body who has one or more of the following features could be diagnosed with Graves’ Disease: 

• Detectable TRABs in the blood

• Evidence of Graves’ Ophthalmopathy and/or Graves’ Dermopathy

• Spread out and increased radioactive iodine uptake.

The lowdown

If you have symptoms of hyperthyroidism, it is recommended that you see your doctor as soon as possible so that a prompt diagnosis can be made. 

Left untreated, Graves’ Disease can result in serious complications such as heart failure, osteoporosis, infertility, and a potentially fatal “thyroid storm” where your heart rate, blood pressure, and body temperature could rapidly rise to dangerous levels.