Graves' Disease – Symptoms, Treatment, the Thyroid Gland, and Diagnosis of the Autoimmune Disease Graves' Disease

The clinical picture of Graves' disease is characterized by three typical symptoms. This trio, known as the Merseburg triad, consists of

• a goiter (struma),
• rapid heartbeat (tachycardia), and
• protruding eyes (exophthalmos, “bulging eyes”).

This is accompanied by an overactive thyroid (hyperthyroidism), meaning excessive production of thyroid hormones.

Graves’ disease can occur at any age. There is an increased risk of the disease developing between the ages of 30 and 60. The condition often first appears during periods of hormonal changes in the body, such as

• puberty,
• pregnancy, or
• menopause.

Women are affected by Graves’ disease significantly more often than men, at a ratio of 6 to 1. About 3 percent of women and about 0.5 percent of men develop Graves’ disease during their lifetime.

The Merseburg triad occurs in about half of all patients. An enlargement of the thyroid gland results in what is known as a goiter. Once it reaches a certain size, it becomes visible on the outside of the neck. Hyperthyroidism accelerates the metabolism, often causing the heart to struggle to keep up. This strain manifests as a rapid heartbeat (tachycardia).

Exophthalmos is a symptom associated with Graves’ disease. In this condition, the eyeball (bulbus) protrudes visibly from the eye socket, while the eyelids gradually recede behind it. Exophthalmos usually occurs in both eyes. However, it is also possible for only one eyeball to protrude.

Exophthalmos, however, is generally classified as a distinct autoimmune disease. Hyperthyroidism merely contributes to its development. Affected individuals lose weight more quickly than other people. However, the opposite is also possible. Hyperthyroidism causes constant ravenous hunger and increased food intake. In people with a relatively slow metabolism, this leads to obesity.

In many cases, hair loss occurs. Muscle strength is reduced, and those affected sweat more. Their physical and mental performance is impaired.

Other typical symptoms include:

• Frequent bowel movements/diarrhea
• Tremors
• Sleep problems
• Shortness of breath
• High blood pressure
• Nervousness
• Sensitivity to heat
• Fertility issues (impotence in men, irregular menstrual cycles in women)

Family history

Studies of twins have shown that Graves’ disease is often genetically determined. A high percentage of susceptibility to the disease is encoded in the genetic material, DNA.

In addition, family trees have been analyzed. They show that about 30 percent of patients have relatives who also have or have had Graves’ disease.

However, environmental factors may also play a role in the onset of the disease. In particular,

• psychological stress,
• tobacco use,
• excessive dietary iodine intake, or
• pregnancy

increase the risk of developing Graves’ disease. In contrast, taking oral contraceptives appears to lower the risk.

Disruption of Metabolic Regulation

Graves’ disease is an autoimmune disorder. This means that the immune system attacks parts of the body itself. In Graves’ disease, the immune system produces antibodies against the receptor for TSH (thyroid-stimulating hormone, thyrotropin).

This disrupts the highly sensitive regulatory cycle for the production of the thyroid hormones thyroxine (T4) and triiodothyronine (T3).

TSH is released by the pituitary gland in the brain. In a healthy person, TSH binds to the TSH receptor on thyroid cells. This, in turn, stimulates the production of the thyroid hormones T3 and T4. These hormones, in turn, indirectly inhibit the production of TSH in the pituitary gland.

Less TSH, in turn, leads to lower levels of thyroid hormones. However, this reduces the inhibition of TSH production. Consequently, more TSH—and, as a result, more thyroid hormones—are produced.

This finely tuned regulatory cycle is disrupted when antibodies bind to the TSH receptor. This leads to inflammation of the thyroid gland. This means that the TSH receptor is now constantly stimulated, resulting in increased secretion of the thyroid hormones T3 and T4. As described above, this leads to an inhibition of TSH production in the brain.

However, because the binding of the antibody to the TSH receptor disrupts the regulatory cycle, more and more T3 and T4 are produced. In addition, the thyroid cells are stimulated to grow. This sustained growth stimulus results in an enlargement of the thyroid gland and the formation of a goiter. The increased release of thyroid hormones then causes the symptoms mentioned above.

However, the antibodies can also cause changes in other parts of the body. In the eye, endocrine orbitopathy (a hormone-related disease of the eye socket) can develop, characterized by the typical “Graves’ bulging eyes” or “protruding eyes” (exophthalmos). Inflammation of the connective tissue in the lower leg is called pretibial myxedema and is also known to result from excessive production of antibodies against the TSH receptor.

The doctor performs a physical examination and evaluates the thyroid gland using ultrasound. This is followed by laboratory tests.

Some symptoms, such as a goiter or exophthalmos, can put the treating physician on the right track early on.

As part of the laboratory tests, TSH, thyroxine (T4), and triiodothyronine (T3) levels in the blood serum are typically measured first. There are also reliable laboratory tests available today to detect the antibody against the TSH receptor that triggers the disease.

If the TSH level is normal, Graves’ disease is unlikely. If the TSH level is too low and the T3 and T4 levels are too high at the same time, hyperthyroidism is present. If antibodies against the TSH receptor are also detected, a diagnosis of Graves’ disease can be made.

If larger nodules are visible on an ultrasound, the doctor will likely order a thyroid scintigraphy for further evaluation.

Thyroid examination via ultrasound © Max Tactic / Fotolia

Treatment begins with antithyroid medications. These drugs inhibit the production of thyroid hormones by blocking the uptake of iodine. In this way, they restore balance to the metabolism.

In addition, beta-blockers are often used to relieve the unnaturally high strain on the cardiovascular system. Once T3 and T4 levels have been lowered to normal ranges, the dose of antithyroid drugs should be reduced. To continuously adjust the dosage on an individual basis, it is important to monitor treatment progress at regular intervals.

The patient can passively support their recovery by

• refraining from physical activity,
• protecting themselves from stress and mental strain, and
• significantly limiting their iodine intake.

Those affected should completely avoid products containing iodine. People who are prone to obesity, in particular, should ensure they follow a healthy, balanced diet. In addition, they should curb frequent cravings (e.g., by drinking enough fluids or practicing meditation). Those suffering from severe weight loss, on the other hand, must ensure they maintain a nutrient-rich diet. This will help them counteract weight loss.

Graves’ disease is highly recurrent, meaning it can return repeatedly even after improvement. Medication is effective in about half of all patients, and the symptoms disappear. Nevertheless, a relapse is possible.

Patients in whom

• treatment with antithyroid drugs is unsuccessful or
• the disease recurs, or
• who suffer from severe side effects,

have two additional options available: radioiodine therapy and surgical removal of thyroid tissue (thyroidectomy).

In radioiodine therapy, the patient must ingest radioactive iodine. This causes the hormone-producing thyroid cells to die in a targeted manner. In the case of

• pregnancy,
• a desire to become pregnant within the next 6 months, or
• if the patient is breastfeeding,

this form of therapy is not possible. In particularly severe cases or when endocrine orbitopathy has reached a critical stage, surgery is the only remaining option. Today, the goal is generally to completely remove the thyroid gland (total thyroidectomy). Otherwise, any remaining thyroid tissue could lead to hyperthyroidism again.

Patients who have had their thyroid gland removed or who have undergone radioiodine therapy must take thyroid hormones for the rest of their lives. Otherwise, they would develop hypothyroidism. However, this treatment is generally well tolerated.

What exactly is Graves’ disease?

Graves’ disease is an autoimmune disorder of the thyroid in which antibodies against the TSH receptor, known as TRAK, are produced. These antibodies stimulate the production of thyroid hormones, resulting in hyperthyroidism. Graves’ disease is an autoimmune disorder in which the body’s own immune system attacks the thyroid cells.

What are the symptoms of Graves’ disease?

Typical symptoms of hyperthyroidism include a rapid heartbeat, weight loss, sweating, and nervousness. Other symptoms of Graves’ disease may include an enlarged thyroid gland and protruding eyeballs. When the eyes are affected, the condition is referred to as endocrine orbitopathy. Symptoms often develop gradually, but can also appear suddenly and be very pronounced.

How is Graves’ disease diagnosed?

If Graves’ disease is suspected, a physical examination and laboratory tests are performed first. TSH, T3, and T4 levels, as well as specific antibodies such as TRAK, are measured. An ultrasound examination of the thyroid gland and, if necessary, additional diagnostic tests confirm the diagnosis of Graves’ disease. The diagnosis of Graves’ disease also takes into account the typical involvement of the eyes.

What treatments are available for Graves’ disease?

Treatment for Graves’ disease usually begins with medication—specifically, thyreostatics, which inhibit the production of thyroid hormones. Alternatively, radioiodine therapy or surgical removal of the thyroid gland may be considered. This so-called definitive treatment is chosen when remission is not achieved or in severe cases. The treatment of hyperthyroidism depends on the severity and the individual’s specific situation.

Does Graves’ disease require lifelong treatment?

Graves’ disease can go into remission, but some patients experience a relapse. In some cases, lifelong treatment is necessary, particularly after surgical treatment or radioiodine therapy. Regular monitoring of thyroid function remains important, as the thyroid hormones T3 and T4 must be regulated on an ongoing basis.