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Graves' disease

Graves-Basedow disease is a form of thyroiditis, an autoimmune disorder that stimulates the thyroid gland, being the most common cause of hyperthyroidism (overactivity of the thyroid). Also known in the English-speaking world simply as Graves' disease, it occurs most frequently in women (8:1 compared to men) of middle age. Symptoms include fatigue, weight loss and rapid heart beat. Because similar antibodies to those stimulating the thyroid also affect the eye, eye symptoms are also commonly reported. Treatment is with medication that reduces the production of thyroid hormone (thyroxin), surgery thyroidectomy or with radioactive iodine if refractory. more...

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Christina Rossetti famously suffered from this disease in later life.

Signs and symptoms

Graves-Basedow disease is a disorder characterized by a triad of hyperthyroidism, goitre, and exophthalmos (bulging eyeballs).

Due to the many physiological actions of thyroid hormone, many symptoms and signs are linked to Graves' disease:

  • Cardiac: cardiac arrhythmias (especially atrial fibrillation), tachycardia (increased heart rate), collapsing pulse and widened pulse pressure (difference between systolic and diastolic BP) and congestive cardiac failure with peripheral edema, ascites, anasarca.
  • Endocrine: weight loss in the presence of increased appetite, intolerance to heat, elevated basal metabolic rate
  • Dermatological: profuse sweating, thyroid acropachy (clubbing) of the fingernails, onycholysis (fingernail destruction), palmar erythema, pretibial myxedema (3 to 5% of Graves' patients, not to be confused with the myxedema of hypothyroidism)
  • Neurological: tremor (especially noticeable on extending the arms), apprehension, weakness, headache, proximal myopathy (difficulty rising from a chair or squatting position) and hyperactive deep tendon reflexes
  • Gastrointestinal: diarrhea (common), vomiting (rare)
  • Ophthalmological: thyroid eye disease (TED) characteristic of Graves disease include lid retraction (Dalrymple sign) above the superior corneoscleral limbus, lid lag (von Graefe's sign), proptosis or forward displacement of the globes, periorbital swelling and chemosis.

Extremely manifested disease that can sometimes be life-threatening is called the thyroid storm.

Diagnosis

On the basis of the signs and symptoms, thyroid hormone (thyroxine or T4, triiodothyronine or T3) and thyroid-stimulating hormone (TSH) are determined in the medical laboratory. Free T4 and Free T3 is markedly elevated, while TSH is suppressed due to negative feedback. An elevated protein-bound iodine level may be detected. A large goiter is sometimes seen on X-rays.

Thyroid-stimulating antibodies may be detected serologically.

Pathophysiology

Most features are due to the production of autoantibodies that bind to the TSH receptor, which is present on the follicular cells of the thyroid (the cells that produce thryoid hormone). These antibodies activate the cells in the same fashion as TSH itself, leading to an elevated production of thyroid hormone.

The infiltrative opthalmopathy (thyroid eye disease) that is frequently encountered has been explained by the expression of the TSH receptor on retroorbital tissue.

The exact cause of antibody production is not known. Viral infection may trigger antibodies against its epitopes, which cross-react with the human TSH receptor. There appears to be a genetic predisposition for Graves' disease, suggesting that some people are more prone than others to develop TSH receptor activating antibodies due to a genetic cause. HLA DR (especially DR3) appears to play a significant role.

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Screen for fetal hyperthyroidism at 24-26 weeks: Graves' disease - Obstetrics
From OB/GYN News, 10/15/03

SAN FRANCISCO -- Women with a history of Graves' disease should be screened for fetal hyperthyroidism at 2426 weeks' gestation, Dr. Ingrid Block advised at a meeting on antepartum and intrapartum management.

These women should have their thyroid-stimulating immunoglobulin (TSI) levels measured at the beginning of pregnancy and again at 24-26 weeks. The results may help confirm a suspicion of fetal hyperthyroidism or prompt further analysis, she said at the meeting, sponsored by the University of California, San Francisco.

In most laboratories, a normal background TSI titer will be less than 130%. A TSI of 350% with a fetal heart rate below 160 beats per minute suggests a low risk for fetal hyperthyroidism, but continued monitoring in these cases is prudent, said Dr. Block of the university.

A fetal heart rate above 160 beats per minute typically characterizes the disease.

A TSI of 350%-500% puts the fetus at moderate risk for hyperthyroidism, and a TSI of more than 500% puts the fetus at high risk.

Fetal hyperthyroidism complicates 1% of pregnancies in U.S. women with a history of Graves' disease. With active maternal disease, most fetuses will be protected by their mothers' antithyroid medication.

Physicians should be especially careful to look for fetal hyperthyroidism in women with a history of Graves' disease who are on thyroid hormone replacement therapy but have discontinued antithyroid medication. These women may still have thyroid-stimulating hormone (TSH)-receptor antibodies, which puts them at highest risk for fetal hyperthyroidism, she said.

In general, a maternal TSH-receptor antibody titer above 350% increases the likelihood that the fetus has hyperthyroidism.

Diagnosis is based on clinical symptoms and ultrasound findings. Ultrasound studies should be ordered for women with a history of Graves" disease to look for fetal, goiter or a hyperextended fetal neck that could indicate goiter.

Growth retardation, increased fetal motility, or accelerated fetal bone maturation also can be signs of fetal hyperthyroidism. If the woman had a previous pregnancy complicated by fetal hyperthyroidism, this also increases the risk for the disease in the current pregnancy.

In rare cases, obtaining a sample of fetal cord blood may be necessary to make the diagnosis, but this procedure carries a 1% risk of fetal loss.

Physicians should therefore weigh the risks and benefits carefully and consult a pediatric endocrinologist before performing this procedure, Dr. Block commented.

ARTICLES BY SHERRY BOSCHERT San Francisco Bureau

COPYRIGHT 2003 International Medical News Group
COPYRIGHT 2003 Gale Group

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