What is Graves Disease

Graves Disease is an autoimmune disorder caused by autoantibodies abnormally stimulating the thyroid cells to produce excessive amount of Thyroid hormones (Thyroxine T4 and Triiodothyronine T3) leading to Hyperthyroidism with its associated signs and symptoms manifesting in many systems and organs of the body such as the eyes, skin, heart and muscles. Graves disease is also called Diffuse toxic Goiter or Basedow’s disease.

Graves Disease occurs when the bodys antibodies (proteins produced by the body to fight infections) turns against the body and starts attacking the Thyroid gland cells leading to manifestation of symptoms. These antibodies are called Thyroid Stimulating Immunoglobulins (TSI) or Thyroid Stimulating Antibodies.

Graves Disease Epidemiology

Graves Disease occurs commonly in females than in males and mostly affects people between the ages of 40 to 60 years; even though it may occur in children too.

Picture of Graves Disease eyes showing the bulging eye balls

Graves Disease Pathophysiology

The Thyroid gland produces thyroid hormones (T4 and T3) by receiving impulse or stimulus or triggers from another hormone produced by the pituitary gland of the brain known as the Thyroid Stimulating Hormone (TSH). Thyroid Stimulating Hormone binds to the Receptors on the Thyroid cells and causes them to produce thyroid hormones in a regulated manner. TSH production is controlled and regulated based on need in the body, hence it functions normally.

In Graves disease, the TSI (that is, the autoantibodies produced by the body) bind to the receptors on thyroid cells and causes the continuous stimulation of the thyroid cells to produce excessive amount of Thyroid Hormones uncontrollably leading to a condition known as Hyperthyroidism (i.e. excessive thyroid action). There are many causes of Hyperthyroidism of which Graves disease is one of the causes. Another cause of Hyperthyroidism is the early phase of Hashimotos Thyroiditis. Graves disease should not be confused with Hashimotos Thyroiditis: both are autoimmune diseases that can all cause hyperthyroidism but Hashimotos Thyroiditis is caused by destruction of the thyroid cells while Graves disease is caused by over stimulation of the thyroid cells.

Graves disease Causes

Causes of Graves disease include:

1. Genetic predisposition (Family History): having a family member with graves disease increases your risk of having the disease. The closer you are related by blood with a relative with Graves disease (such as identical twins), the more likely you will get.
2. Women are at increased risk of having Graves disease than men.
3. Presence of some autoimmune disorders (such as Type 1 Diabetes Mellitus) could predispose you to having Graves disease
4. Smoking also predisposes you to having Graves disease
5. Pregnancy increases risk
6. Emotional or physical stress
7. Apart from these risk factors, the exact cause of Graves disease is not known and what triggers the autoimmune antibodies is not known, also see Hyperemesis Gravidarum causes.

Picture of Signs and Symptoms of Graves Disease according to the different symptoms associated with each system of the body

Graves disease Symptoms

1. Weight loss despite increased appetite
2. Feeling of the heart beating (Palpitation)
3. Itching
4. Hair loss
5. Difficulty in sleeping (Insomnia)
6. Chest pain
7. Shortness of breath or difficulty in breathing
8. Hyperdefecation (increased in the number of times you go to the toilet with or without diarrhea)
9. Altered menstrual cycle (prolonged menstrual period)
10. Heat intolerance (feeling hot when other people are feeling normal)
11. Fatigue
12. Irritability and anger problems (easily getting angry)
13. Swelling of neck (front aspect of the neck)
14. Erectile dysfunction
15. Loss of interest in sex (loss of libido)
16. Difficulty in swallowing or eating when the neck swelling is big

Graves disease Signs

1. Bulging eyes
2. Anxiety
3. Restlessness
4. Sweating
5. Fine Tremors (unintentional shaking of hands)
6. Irregular heart beat (arrhythmias)
7. Vision problems or visual changes
8. Elevated blood pressure
9. Goiter

Picture of a woman having Graves disease with neck swelling

Graves disease Clinical Examination Findings

Whenever a patient with Graves disease sees a doctor, the doctor tries to find out about the History of the disease by asking questions, he or she then examines you to pick some signs and then request for laboratory test(s) to confirm the diagnosis. In carrying out the clinical examination of a patient with Graves disease, the following signs may be seen;

1. The patient is anxious and may be restless.
2. The eyes are seen bulging
3. Difficulty in squatting and standing up by self (proximal myopathy), or difficulty in tying head scarf.
4. Swelling of the neck
5. Presence of Tremors of the hands
6. Enlarged lymph nodes may be felt
7. The upper parts of the legs may be swollen and thick (pretibial myxedema)

Graves disease Laboratory Investigations

Thyroid Function Test (TFT) and TSI

A blood test is requested known as Thyroid Function Test (TFT) and it measures the amount of Thyroid Hormones (T3 and T4) in the blood and also the level of TSH (Thyroid Stimulating Hormone). When the TSH is low with T3 and T4 being High then it shows Hyperthyroidism. When there is presence of the Thyroid Stimulating Immunoglobulins (TSI), then a diagnosis of Graves disease is made.

Radioactive Iodine Uptake Test and Scan

A radioactive pill or tablet is given to the patient to take and a scan is done after few hours. It may be repeated after 24 hours. When you have Graves disease which is a cause of a hyperactive thyroid, this causes the thyroid gland to absorb more of the iodine taken and it is seen on the scan.

Graves disease Diagnosis

A diagnosis of Graves disease is made when the blood test result shows the presence of autoantibodies against thyroid cells in the body with associated increased levels of T4 and T3 thyroid hormones and low levels of TSH.

Graves disease treatment

Treatment for Graves disease includes use of medications (anti thyroid drugs), use of radioactive iodine or surgery.

Drugs for Treating Graves disease

1. Methimazole
2. Carbimazole
3. Propyithiouracil
4. Beta blockers (propranolol) to help with arrhythmias

Use of drugs for treatment of Graves disease may not cure the disease permanently as there could be reoccurrence after stopping the drugs. Complications may also occur following the use of these drugs such as agranulocytosis, granulocytopenia or aplastic anemia which cause severe infections.

Radioactive iodine for treatment of Graves disease

This form of therapy is good especially when there is failure to achieve cure following the use of Antithyroid drugs. However, it can cause Hypothyroidism as a complication and should never be done in women in pregnancy.

Treatment for Graves disease by use of Surgery

When there is failure of medical treatment, presence of respiratory compromise (difficulty in breathing or swallowing), suspicion of cancer or in a pregnant woman with large goiter, then surgery may be needed. Complication due to surgery may include loss of voice if the recurrent laryngeal nerve is affected (the loss of voice may also develop even before the surgery if a cancer is involve or hoarseness of voice if the swelling puts pressure on this nerve). Other complications may include hypothyroidism following the surgery.

Graves disease Prognosis and Complications

How serious is Graves Disease?

Without treatment, Graves Disease may lead to serious complications and even some are life threatening.

1. Arrhythmias (abnormal heart rates)
2. Stroke may occur especially with atrial fibrillation
3. Increased risk of giving birth to babies with birth defects
4. Increased risk of miscarriages
5. Easy fracture of bones (osteoporosis)
6. Blindness may occur following inability to close the eyes due to bulging eye balls with subsequent dryness and excoriation
7. Thyroid storm (also called accelerated hyperthyroidism or thyrotoxic crisis): this is rare, but when it occurs, it needs immediate medical attention or death may occur. It is characterized by fever, vomiting, profuse sweating, diarrhea, altered consciousness, seizures, severe weakness, irregular heartbeat (arrhythmias), jaundice (yellow discoloration of the eyes), severe low blood pressure and coma.