What is Graves’ Disease?

When it comes to disorders affecting the thyroid, Hashimoto’s thyroiditis is most commonly discussed.

Although widely prevalent, Hashimoto’s disease is not the only problem that has a major impact on thyroid functioning.

Let’s not forget about Graves’ disease.

What is it?

What is the cause of this disease?

The main objective of this article is to elucidate this health problem and help you recognize the signs associated with it.

(By the way if some terms are unfamiliar to you, it might be helpful to check out the Common Thyroid Question and Answers page here.)

What is Graves’ disease?

Graves’ disease is defined as an autoimmune condition that causes the thyroid gland to overproduce hormones.

Other terms that refer to this disease include autoimmune hyperthyroidism and toxic diffuse goiter.

The autoimmune disease is one of the most common causes of hyperthyroidism in the United States, according to the American Thyroid Association[i].

In Graves’ disease, the immune system creates antibodies called thyroid-stimulating immunoglobulins.

Later, these antibodies bind to healthy thyroid cells and induce overproduction of thyroid hormone.

Hormones produced by the thyroid gland affect many functions in the body including the nervous system, brain development, body temperature, metabolism, and so much more.

When left untreated, Graves’ disease can lead to numerous complications and further amplify hyperthyroidism, thus affecting our overall quality of life.

History of Graves’ disease

In the ancient times or more precisely in the 5th century BC, Aristotle and Xenophon mentioned the phenomenon called exophthalmos (the bulging of the eye) in their writings.

In 1110 AD, Abu-l-Fadail Ismail ibn al-Husain al Jurjani from Persia wrote about the combination of exophthalmos with goiter, but it is impossible to determine whether he described Graves’ disease or not.

Later, in the 18th and 19th century there were a few reports of patients with both goiter and exophthalmos, but authors couldn’t understand how they are connected to one another.

For years, scientists kept finding both goiter and the bulging eye symptom but still didn’t know how they are associated.

During the academic year 1834-1835, Robert James Graves described three women with goiter and palpitations at the Meath Hospital in Dublin, Ireland he didn’t know what was going on with them.

These women didn’t have prominent eyes, but a combination of seemingly random symptoms.

At that point, he heard of a fourth patient observed by one of his closest colleagues and friends William Stokes. The fourth patient had the bulging eye symptom.

The same year, in 1835, Graves published the report where he described a syndrome with goiter, tachycardia, and exophthalmos[ii].

The report which described a new health condition which combines these symptoms was a part of the London Medical Society Clinical Lectures[iii].

Although the disease which eventually leads to hyperthyroidism is named after Graves, it is theorized he wasn’t the first one to describe it.

Caleb Hillier Parry is thought to be the first scientist to describe hyperthyroidism in 1786, but his observations were published by his son in 1825, three years after his death.

Despite having the disease named after him, the most notable contribution of Graves to the world of medicine is the role of a lecturer.

Prevalence of Graves’ disease

As mentioned above, Graves’ disease is the most common cause of hyperthyroidism. Evidence shows the annual incidence in the US is 20 to 50 cases per 100,000 persons.

The lifetime risk of developing Graves’ disease is 3% for women and 0.5% for men[iv].

In other words, 2% to 3% of the population or 10 million people have this autoimmune condition.

Prevalence of Graves’ could be even higher if we bear in mind that many people experience all the symptoms but aren’t diagnosed yet or they refuse to see the doctor.

Causes of Graves’ disease

Similarly, to Hashimoto’s thyroiditis, this cause of this disease is malfunctioning of the body’s immune system.

The healthy immune system produces antibodies whose goal is to target viruses, bacteria, and other foreign invaders.

In Graves’ disease, the immune system releases antibodies that attack healthy thyroid cells.

That being said, the underlying cause is unknown[v].

At this point, scientists still don’t know what makes the immune system behave that way. That is a major problem with all autoimmune diseases, that we still don’t know what causes them.

What we do know is that heredity plays a role in the development of this condition, but most likely a combination of environmental and genetic factors could propel malfunctioning of the immune system.

Risk factors

Everyone can develop Graves’ disease, but it doesn’t mean you will.

Some people are at a higher risk than the others. Here are the most common risk factors associated with this autoimmune condition:

  • Heredity, the odds of developing the disease is higher if your family members have Graves’ disease or some other autoimmune condition
  • Being a woman; ladies are about 7 to 8 times more susceptible to developing Graves’ disease than men[vi]
  • You are in the 30-50 age group
  • Having some other autoimmune disease (rheumatoid arthritis, lupus, type 1 diabetes, etc.)
  • Experiencing trauma, stressful events and illnesses
  • Being pregnant or giving birth to a baby recently
  • Smoking[vii]

Symptoms of Graves’ disease

Numerous symptoms are associated with Graves’ disease.

Since this autoimmune condition is the most common cause of hyperthyroidism, many signs and symptoms are associated with those of overactive thyroid gland.

However, patients also experience various symptoms that aren’t related to hyperthyroidism.

Signs and symptoms of Graves’ disease include:

  • Change in menstrual cycle
  • Fatigue
  • Frequent bowel movements
  • Goiter (enlargement of thyroid gland)
  • Graves’ dermopathy (thick, red skin primarily affecting tops of the feet and shins)
  • Graves’ ophthalmopathy (bulging eyes)
  • Heat sensitivity, warm or moist skin
  • Increase in perspiration
  • Irritability and anxiety
  • Palpitations (rapid or irregular heartbeat)
  • Problems with erections
  • Reduced libido
  • Tremor of hands or fingers
  • Weight loss without changing diet habits

Graves’ dermopathy

Graves’ dermopathy is defined as a classical, but an uncommon manifestation of Graves’ disease.

It is indicated by thickening and reddening affecting the skin, particularly on tops of a patient’s feet or their shins.

Evidence shows this symptom occurs in 0.5% to 4.3% patients who suffer from this autoimmune condition. Moreover, dermopathy is almost always associated with Graves’ ophthalmopathy.

Dermopathy is asymptomatic and doesn’t lead to any complications; it is mainly a cosmetic concern.

Besides shins and feet, reddening and thickening of the skin can occur in areas such as shoulders, upper back, and upper extremities[viii].

Graves’ ophthalmopathy

Graves’ ophthalmopathy, also called as Graves’ orbitopathy, is a sight-threatening ocular disease.

It usually affects people with hyperthyroidism or hyperthyroidism due to Graves’ disease[ix].

In fact, about 30% of people with Graves’ experience this symptom.

The ocular disease is caused primarily by inflammation – which is why it is so visible and disheartening to those who have it. However, other immune system events can also cause muscles and other tissues around the eyes to ‘pop out’ in a sense and make your eyes bulge.

Signs and symptoms of Graves’ orbitopathy include:

  • Double vision
  • Exophthalmos (bulging eyes)
  • Gritty sensation in the eyes
  • Inflamed or reddened eyes
  • Loss of vision
  • Pain or pressure in the eyes
  • Retracted or puffy eyelids
  • Sensitivity to light

Complications

Graves’ disease is linked to a number of complications, but the risk of experiencing them increases when this condition is left untreated.

Here are the most common complications associated with the autoimmune disease:

  • Brittle bones
  • Heart conditions: congestive heart failure, heart rhythm disorders, alterations affecting function and structure of heart muscles
  • Pregnancy issues: miscarriage, preterm birth, fetal thyroid dysfunction, poor fetal growth, preeclampsia, and maternal heart failure
  • Thyrotoxic crisis (thyroid storm), a potentially life-threatening event which refers to dangerously high levels of thyroid hormones

How is Graves’ disease diagnosed?

It can be difficult to diagnose Graves’ at the beginning because most symptoms are linked with many other conditions, except bulging eyes.

Ideally, you should mention all symptoms you experience to the doctor and inform him/her whether you or your family members have an autoimmune disease or a history of thyroid disorders.

To diagnose the problem and rule out some other health conditions, the doctor will perform a physical exam and order different tests, including:

  • Blood sample – to determine the concentration of TSH (thyroid stimulating hormone). Patients with Graves’ have higher levels of thyroid hormones and lower levels of TSH and. Blood sample can also be used for TSI (thyroid stimulating immunoglobulin) test, patients with Graves’ have this antibody in their blood
  • RAIU (radioactive iodine uptake) test – measures the concentration of iodine the thyroid receives from the bloodstream. Excessive levels of iodine uptake point to Graves’ disease
  • Imaging tests – these are usually recommended when other diagnostic measures didn’t give conclusive results. Imaging tests patients can do include x-ray, CT, MRI
  • Ultrasound – shows whether there is an enlargement of a thyroid gland

How is Graves’ disease treated?

The primary objective of the Graves’ disease treatment is to stop the overproduction of thyroid hormones and block their impact on your health and body.

Patients who suffer from this autoimmune disease have three options: medications, thyroid surgery, or radioiodine therapy.

Radioiodine therapy

This is the most common treatment option for Graves’ disease.

The therapy requires taking radioactive iodine-131 by mouth. The thyroid gland collects iodine for hormone production, and it will also collect radioactive iodine as well.

That being said, iodine-131 gradually destroys the cells that make up the gland without affecting the tissues.

Although effective, the therapy isn’t recommended for patients with eye problems because it could contribute to Graves’ ophthalmopathy

Medications

Your doctor may also prescribe anti-thyroid drugs that interfere with use of iodine by thyroid for production of hormones.

The most commonly used medications are methimazole and propylthiouracil.

Potential side effects linked with the use of these drugs are joint pain, rash, reduced level of disease-fighting white blood cells, and liver failure.

Along with anti-thyroid medications, patients with Graves’ disease may also be instructed to take beta blockers.

They function to reduce symptoms of hyperthyroidism including rapid heartbeat, tremors, and nervousness. It goes without saying that beta blockers have no influence on hormone production.

Surgery

The surgical procedure is recommended to patients who don’t experience relief from other treatment options.

The surgery includes removing all or a part of the thyroid. After the procedure, patients are required to supply their body with sufficient level of thyroid hormones. There are some risks with this treatment as well.

The surgery carries a potential side effect which includes damaged nerve that regulates parathyroid glands (tiny glands next to thyroid) and your vocal cords.

Eye care

As seen above, patients who suffer from Graves’ disease may also struggle with eye problems.

During the day, mild ophthalmopathy can be treated with eye drops, available in all pharmacies and drugstores in over-the-counter form, and at night the use of lubricating gels is recommended. For more severe symptoms, the physician may suggest:

  • Corticosteroids to reduce swelling behind the eyeballs
  • Orbital decompression – a surgery to remove the bone located between sinuses and the eye socket
  • Orbital radiotherapy – involves X-rays to destroy a specific area of tissue behind eyes
  • Prisms in glasses to correct double vision

Conclusion

Graves’ disease is a common autoimmune condition that leads to hyperthyroidism.

In fact, Graves’ is one of the most prevalent cause of hyperthyroidism in the US.

The condition is caused by the immune system attacking healthy cells, but different treatments are available to help manage symptoms and inhibit hormone production.

References

[i] Graves’ disease, American Thyroid Association https://www.thyroid.org/graves-disease/

[ii] Volpe R, Sawin C. Graves’ disease – a historical perspective. Endocrine Updates, vol. 6, 1-8 https://link.springer.com/chapter/10.1007%2F978-1-4615-4407-4_1

[iii]Clinical lectures delivered by Robert J. Graves, London Medical and Surgical Journal, 1834-5, 516 https://archive.org/stream/p2londonmedicals07londuoft#page/512/mode/2up

[iv] Longo DL. Graves’ disease. New England Journal of Medicine October 2016, 375:1552-1565. Doi: 10.1056/NEJMra1510030 http://www.nejm.org/doi/full/10.1056/NEJMra1510030?rss=searchAndBrowse

[v] Graves’ disease, Healthline.com http://www.healthline.com/health/graves-disease#overview1

[vi] Graves’ disease, National Institute of Diabetes and Digestive and Kidney Diseases https://www.niddk.nih.gov/health-information/endocrine-diseases/graves-disease

[vii] Prummel MF, Wiersinga WM. Smoking and risk of Graves’ disease. JAMA 1993;269(4):479-482. Doi: 10.1001/jama.1993.03500040045034 http://jamanetwork.com/journals/jama/article-abstract/403015

[viii] Reddy SVB, Gupta SK, Jain M. Dermopathy of Graves’ disease: Clinico-pathological correlation. Indian Journal of Endocrinology and Metabolism. 2012;16(3):460-462. doi:10.4103/2230-8210.95714. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3354863/

[ix] Bahn RS. Graves’ Ophthalmopathy. The New England journal of medicine. 2010;362(8):726-738. doi:10.1056/NEJMra0905750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3902010/

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