Grave's Disease Complete Overview

What is Grave’s Disease?

Grave's disease is an immune system disorder and it results in the excess production of thyroid hormones causing hyperthyroidism. It is an autoimmune disease. Signs and symptoms of Grave's disease can be wide ranging. Treatment aims at reducing the amount of thyroid hormones that the body produces and to lessen the symptoms caused by the condition.

• Grave's disease is also known as “Toxic diffuse goiter”.
• About 25 to 30% of the patients suffer from eye problems.
• The exact cause though is not known for sure; it is believed.

Etiology

The exact cause of Grave's disease is not known. A trigger causes the immune system to overproduce an antibody called thyroid-stimulating immunoglobulin (TSI). The trigger may be a combination of genetic predisposition and environmental factors such as:

• Stress
• Pregnancy
• Virus/infection

Genetic Predisposition

Some people are more prone to TSH receptor activating antibodies due to genetic causes. In such people, a genetic predisposition for Grave's disease is seen. Human leukocyte antigen DR (Mostly DR3) plays a role in this. Genes involved include those for:

• Thyroglobulin
• Thyrotropin receptor
• Protein tyrosine phosphatase non receptor type 22 (PTPN22)
• Cytotoxic T-lymphocyte-associated antigen 4

Risk Factors

• Family history of thyroid disease.
• Smoking cigarettes
• Sex of the individual (More common among women)
• Pregnancy
• Emotional or physical stress.
• Autoimmune diseases like:
  • Rheumatoid arthritis
  • Lupus
  • Celiac disease
  • Vitiligo
  • Type 1 diabetes

Epidemiology

• Grave's disease mostly affects females more than males.
• Mostly seen in people between 30 to 50 years.
• It can also affect children and older adults.
• Occurs in 0.5% of people.
• Lifetime risk for women: Around 3%
• Lifetime risk for men: Around 0.5%
• It is one of the most common causes of hyperthyroidism.

Pathophysiology

• The body produces IgG autoantibodies which are directed against the thyrotropin receptor.
• These antibodies cause hyperthyroidism by binding and in turn stimulating the TSHr.
• The TSHr is expressed on the thyroid follicular cells of the thyroid gland.
• The chronic stimulation leads to an increase in the production of T3 and T4.
• This in turn causes hyperthyroidism and the enlargement of thyroid gland which becomes visible as goiter.
• Swelling of the eyeballs is a result of the binding of the antibodies to the extraocular muscles.
• Orange peel skin is caused due to the infiltration of antibodies under the skin which causes inflammatory reaction and fibrous plaques.
• The three types of autoantibodies to the TSH receptor are:
  • Thyroid stimulating immunoglobulins
  • Thyroid growth immunoglobulins
  • Thyrotropin binding-inhibiting immunoglobulins

How Can We Diagnose Grave’s Disease?

Clinical Features

• Anxiety and irritability
• A fine tremor of fingers and hands
• Enlargement of the thyroid gland
• Weight loss despite normal eating habits
• Change in menstrual cycle
• Bulging eyes
• Fatigue
• Thin and red skin usually on the shins or tops of the feet (Grave's dermopathy)
• Sleep disturbance
• Unable to resist heat and increase in perspiration.
• Reduced libido
• Frequent bowel movements
• Rapid and irregular heart beat

What is Grave’s Ophthalmology?

Graves ophthalmopathy is caused as a result of the accumulation of carbohydrates in the muscles and tissues behind the eyes. The cause of this phenomenon is unknown.It can occur at the same time as hyperthyroidism or several months later. It can occur even in the absence of hyperthyroidism.

Investigations

Grave's disease can be easily diagnosed based on the symptoms and medical and family history. More accurate diagnosis is done with the help of the following methods:

Thyroid Hormone Tests

The T3, T4 and TSH levels in the blood are tested.

Testing TSH Levels

• This is usually the first test prescribed by the doctor in order to investigate Grave's disease.
• TSH level will be extremely low if you have Grave's disease.
• This is because the pituitary gland tries to compensate for the low levels of T3 and T4 hormones.

Testing Total T3 and T4 levels

• Patients with Grave's disease will have high levels of T4 and T3 in their blood.
• Because the antibody TSI misdirects the thyroid gland to produce excess T3 and T4 hormones.

Testing Free T4 Levels

• Free T4 test is run if the TSH level in the blood is found to be abnormal.
• Total T4 may be altered by blood proteins that bind to the T4 hormone.
• Free T4 is less affected by blood proteins.
• Hence, they give a more accurate picture of thyroid function and dysfunction.

Antibody Tests

The following antibodies are tested in the antibody tests:

• Thyroid-stimulating Immunoglobulin (TSI) levels.
• Thyroid peroxidase (TPO) antibodies levels.

Radioactive Iodine Uptake (RAIU) and Scan

• It measures the amount of iodine absorbed by the thyroid gland.
• RAIU involves the intake of an iodine pill called radioactive tracer 4 to 6 hours before the first thyroid gland scan.
• The scan is repeated after 24 hours.

Other Tests

Other tests may include:

• CT scan
• MRI
• Ultrasound of the eye and eye sockets

What are the Complications of Grave’s Disease?

• Pregnancy issues: Such as miscarriage, preterm birth, foetal thyroid dysfunction, poor foetal growth, maternal heart failure and preeclampsia.
• Heart disorders
• Thyroid storm : also known as accelerated  hyperthyroidism or thyrotoxic crisis. Likely to happen when severe hyperthyroidism is left untreated and can cause effects such as sweating, vomiting, diarrhea, delirium, seizures, irregular heartbeat, jaundice etc.
• Brittle bones

How Can We Treat Grave’s Disease?

Treatments of Grave's disease include:

Beta-Blockers

• Beta-blockers such as propranolol and metoprolol are considered as the first line treatment of Grave's disease.
• These medications protect the heart until other hyperthyroidism treatments take effect.
• Beta-blockers do not cease thyroid hormone production.

Antithyroid Medications

• Examples of antithyroid medications are methimazole and propylthiouracil.
• They cease thyroid hormone production.
• Skin rashes and low WBC count are rare side effects of these medications.
• Liver disease may also occur as a side effect even though rarely.

What is Radioiodine Therapy?

This management method involves the intake of a radioactive iodine pill. Thyroid gland cells are destroyed over a period of 2 to 3 months. Thus, the thyroid gland shrinks gradually, decreasing the production of thyroid hormones as a result. The rest of the body other than the thyroid gland is not affected in radioactive iodine therapy.

Surgery

• All or part of the thyroid gland is removed as a part of thyroidectomy.
• Hypothyroidism may occur post thyroidectomy in some people which can be dealt with by thyroid replacement.

Prognosis of Graves Disease

The prognosis of Grave's disease is generally good.

• People who undergo treatment for Grave's disease (Radioactive iodine for thyroidectomy) will eventually develop hypothyroidism.
• Antithyroid drugs are usually taken lifelong for grave's disease.

Important Points to Remember about Grave’s Disease

• Grave's disease is also known as “Toxic diffuse goiter”.
• About 25 to 30% of the patients suffer from eye problems.
• Grave's disease mostly affects females more than males.
• Mostly seen in people between 30 to 50 years.
• It can also affect children and older adults.

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