Graves' Disease

Graves’ Disease

Hyperthyroidism or Graves’ disease (or Basedow Disease in Europe) is autoimmune disorder with symptoms directly related to hormone excess - hyperthyroidism. Hyperthyroidism is the medical term for an overactive thyroid. In people with hyperthyroidism, the thyroid gland produces too much thyroid hormone. When this occurs, the body's metabolism is increased, which can cause a variety of symptoms. It manifestations consist of hyperthyroidism, goiter, eye disease (orbitopathy or Graves´ ophthalmopathy) and occasionally a dermopathy. Graves' disease has an unpredictable clinical course. The diseases cluster in families and are more common in women.
Please see more information on the following page: Graves’ Disease Center

What are symptoms of hyperthyroidism

Most people with hyperthyroidism have symptoms. Symptoms directly related to hormone excess
including one or more of the following:

* Anxiety, irritability, trouble sleeping

* Weakness (in particular of the upper arms and thighs, making it difficult to lift heavy items or climb stairs)

* Tremors (of the hands)

* Perspiring more than normal, difficulty tolerating hot weather

* Rapid or irregular heartbeats

* Fatigue

*Weight loss in spite of a normal or increased appetite

* Frequent bowel movements

* Manifestations in connective tissue: Graves´ ophthalmopathy and dermopathy

In addition, some women have irregular menstrual periods or stop having their periods altogether. This can be associated with infertility. Men may develop enlarged or tender breasts, or erectile dysfunction, which resolves when hyperthyroidism is treated.

What is the incidence of hyperthyroidism and what are predisposing factors

The annual incidences of Graves’ Disease is 40 per 100,000 in the US. It is 4 to 6 times are more common in females then in males, and it is mostly developed between age 20 to 50. 1% to 5% of patients with Graves’ Disease are children (peak at age 11 to 14 years)
It has a strong hereditary and genetic component.

Smoking is weakly associated with Graves’ Disease but strongly with the development of Graves ophtalmopathy

How to make a diagnosis of hyperthyroidism

The most cost-effective screening test is measurement of serum TSH. If the value is normal, the patient is very unlikely to have hyperthyroidism. The serum TSH concentration alone cannot determine the degree of biochemical hyperthyroidism; serum free T4 and T3 are required to provide this information. Typically, the thyroid hormone level is high and the TSH level is low. A thyroid scan may also be recommended to help determine the cause of hyperthyroidism (Graves' disease, toxic nodular goiter, or thyroiditis).

What are treatment options?

1. Medications:

Anti-thyroid medication such as Methimazole (MMI or Tapazole) and Propylthiouracil (PTU). work by decreasing how much thyroid hormone the body makes. Both are very effective, but methimazole is preferred because of a greater risk of serious side effects with PTU. These medications can be used as a short and a long term (up to 1 to 2 years) treatment for Graves' disease. The disease goes into remission in about 30 percent of people, and antithyroid drugs can be used to control hyperthyroidism while waiting to see if remission occurs. Antithyroid drugs have some minor side effects, such as rash, hives, painful joints, fever, and stomach upset. A more serious complication called agranulocytosis (lack of white blood cells) and liver failure can occur. White blood cell count and liver function should be frequently checked while patient is taking these medications.

Beta-blockers, such as atenolol, are often started as soon as the diagnosis of hyperthyroidism is made. While beta-blockers do not reduce thyroid hormone production, they can control many of the bothersome symptoms, such as rapid heart rate, tremors, anxiety, and heat intolerance. Once the hyperthyroidism is under control (with antithyroid drugs, surgery, or radioactive iodine), the beta-blocker is stopped.

2. Radioactive iodine ablation

Destroying the thyroid with radiation, called radioiodine ablation, is a permanent way to treat hyperthyroidism. The amount of radiation used is small. Radioiodine is given in liquid or capsule form, and it works by destroying much of the thyroid tissue. This takes about 6 to 18 weeks. People with Graves' disease may have their eye symptoms worsen after therapy and it is contraindicated with Graves’ ophthalmopathy. Also females who want to became pregnant and children should not be given radioactive iodine.

3. Total Thyroidectomy.

If surgery is considered, the evidence-based criteria support total thyroidectomy (rather then partial or subtotal) as the surgical technique of choice for Graves' disease.

The benefits of the surgery would include a quick recovery from the disease, absence of toxic effect from medical therapy or radioactive iodine therapy. The downside to surgical therapy would include small, 1% in a hands of experience surgeon, rate of complications and presence of a small scar. These would include 1% rate of hoarseness (injury to the vocal cords nerve), 1% low calcium level, and 0.5% rate of bleeding or infection. In hands of the experience thyroid surgeon those side effects is minimal and scar is very small, as opposite to low volume surgeon when complication rate could be approaching 10%.

Available evidence supports surgery in the presence of severe Graves' ophthalmopathy. Children with Graves' disease should NOT be treated with an ablative radioactive iodine therapy, and if medical therapy is unsuccessful, the next step should be a surgery. Data on long-term cancer risk are missing or conflicting and until Radioactive iodine ablation has proven harmless in children, recommendation is to perform surgery in this group.

Absolute indications for surgery include the following:

Presence of Graves' disease and an associated suspicious or malignant thyroid nodule

Local compressive symptoms

Children (especially before age 5 yo)

Pregnancy, not controlled with anti-thyroid medication

Unresponsiveness to medical therapy for more then 2 years.

Side effects of medical management (bone marrow suppression or liver dysfunction as result of anti-thyroid medication side effects)

Patients desiring pregnancy (within a year)

Recurrence after treatment with anti-thyroid medications

Fear of radioactive iodine

Relative indication for surgery include following:

Rapid control of symptoms

Large goiter with low iodine uptake

Sever ophthalmopathy

Poor compliance with medical therapy

Preoperative preparation treatment with anti-thyroid drug of the patient with Graves' disease is crucial to avoid intraoperative or postoperative complications associated with anesthesia or surgery. Patients that were treated with Methimazole &/or Propylthiouracil, preoperatively had a 142-fold decreased rate of intraoperative blood loss. Lugol solution given prior to surgery has shown to decreased thyroid vascularity, and 9.33-fold decreased rate of intraoperative blood loss during thyroidectomy. Total thyroidectomy is procedure of choice for surgical treatment of Graves’ disease.

History and Discovery of Graves Disease

1) In English speaking world: an eminent Irish surgeon, Robert James Graves, described a case of goiter with exophthalmos in 1835

2) In Europe; the German physician, Karl Adolph von Basedow, independently reported the same constellation of symptoms in 1840

3) Caleb Hillier Parry was a notable provincial physician in England of the late 18th century, he first noted this condition in 1786. This case was not published until 1825, but was still 10 years ahead of Graves.

Zayn al-Din Sayyed Isma‘il ibn Husayn Gorgani (1040–1136). However, fair credit for the first description of Graves' disease goes to the 12th century Persian physician Sayyid Ismail al-Jurjani. He wrote the Persian medical encyclopedia, Thesaurus of the Shah of Khwarazm, some time after 1110 where he noted the association of goiter and exophthalmos

For mot information please see Graves’ Disease Center and Graves' Disease & Thyroid Foundation


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