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Graves' Disease
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Prepared by: Daniela Cihakova MD, PhD
Definition: Autoantibodies against TSH receptor (Anti-TSH-R) bind to the receptor and stimulate it, causing a non-suppressible overproduction of the thyroid hormone—hyperthyroidism.
Description: Hyperthyroidism caused by the overproduction of thyroid hormones is responsible for the main symptoms of Grave’s disease. Body metabolism is increased, with the catabolic process being increased more then the anabolic one. Inflammation of the thyroid gland is responsible for its growth. Autoimmune stimulation is also responsible for eye protrusion.
Symptoms: - Goiter: an enlargement of thyroid gland
- Eye-related symptoms: protruding eyes, less frequent blinking (this is sometimes described as a “staring appearance”), abnormally retracted eyelids, double vision, itching, and weeping
- Skin -related symptoms: swelling around the eyes with darker color of skin
- Other symptoms:
- weight loss despite increased appetite,
- diarrhea,
- emotional disequilibrium,
- heat intolerance,
- loss of hair,
- menstrual irregularity,
- feeling hot all the time
Diagnosis: - Thyroxine, T3 and T4, are elevated,
- TSH low,
- autoantibodies anti-TSH-R present
- Thyroid scan: thyroid uptake of radioactive iodine isotope is increased.
- CT or MRI of eye sockets
Incidence: Grave’s disease is one of the most common autoimmune diseases. Women are affected more than men, most frequently between the ages of 20 and 40, but the disease can occur at any age. The incidence is 0.5 cases per 1000 individuals.
Treatment: - Antithyroid drugs (propylthiouracil or methimazole): act by blocking the production of the thyroid hormone.
- Surgery: subtotal thyroidectomy or treatment by radioactive iodine. Hypothyroidism after both procedures is common.
- Beta-blocker for symptomatic relief of hypertension, tachycardia, tremor
- Orbital decompression surgery
Pathogenesis: Grave’s disease is an autoimmune disease. Anti-TSH-R is a causative agent of hyperthyroidism in Grave’s disease. Autoanribodies against TSH receptor are probably responsible for Grave’s opthalmopathy (GO) as well. The immunopathogenesis of GO is not known. It seems that the fibroblasts are primary target of the autoimmune attack. Recently, TSH-R was found on fibroblast, opening the possibility that Anti-TSH-R attack the same antigen in the thyroid gland and behind the eye. Below is the evidence that Grave’s disease is autoimmune disease:
Circumstential evidence:
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HLA II class involvement – DR3 is predisposing for Grave’s disease, while DR4 is protecting
- The disease runs in families.
- Presence of autoantibodies in patient’s sera.
Indirect evidence:
Mouse model:
- AKR/N (H-2k) mice were immunized with clone of fibroblasts expressing both the human TSH receptor (hTSHR) and murine major histocompatibility complex (MHC) class II molecules. This immunization induced functional TSHR autoantibodies that either stimulated or blocked the mouse thyroid gland. A transfer experiment was also successful.
- Another murine model of Grave’s disease was developed after BALB/c mice were immunized by i.m. injection with adenovirus expressing thyrotropin receptor (TSHR).
Direct evidence:
A transfer of antibodies from a patient to a healthy person can result in the disease, which can be seen in infants of mothers with Grave’s disease. These infants develop temporary signs of the disease due to a transplacental transfer.
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Links to other Resources:
thyroid-ripken.med.jhu.edu
www.thyroid.org
www.ngdf.org
www.thyroidfoundation.org
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