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Vermaak en Vennote CPD March 2015

Compiled by: M Fourie

Grave’s Disease

Graves' disease is an in which the patient's own immune system attacks the gland, causing it to produce too much thyroxine (FT4). Graves' disease is a form of . When FT4 levels are high the patient's metabolic rate increases; this can have an effect on their physical appearance as well as moods.

Healthy people’s immune systems attack pathogens, organisms and substances that are bad for us eg: bacteria. In an autoimmune disease a person’s immune system starts to attack normal healthy tissue. The thyroid gland is a butterfly gland situated in the below the adams apple. The thyroid gland is part of the endocrine system and produces hormones that regulate metabolism. The thyroid gland produces 2 hormones thyroxine (FT4) and triiodothyronine (FT3). FT4 affects many body systems and has a key role in regulating our body's metabolic rate - the rate at which chemical reactions occur in our body; the rate at which our bodies break things down to produce energy, and build new tissue (metabolism).

Graves disease can occur at any age in women and men but more commonly affetcs women aged 20 or older. This disease can cause the thyroid gland to enlarge to twice its normal size known as a goitre. Graves disease can also affect the eyes, causing bulging eyes (). Symptoms of Graves disease:

 Anxiety  Moodiness and irritability  Insomnia  Tiredness  (irregular heart beat)  (accelerated heart beat)  in the hands and fingers  Sensitivity to heat  Weight loss, even though the patient eats properly  Brittle hair  Goitre (thyroid gland is enlarged)  Menstrual cycle changes  Bowel movements are more frequent

Cause

Thyroid stimulating antibodies binds to the TSH receptor found on the thyroid gland and chronically stimulates it and results in high production of . TSH level will decrease in the blood plasma. The TSH levels fall because the hypothalamus-pituitary-thyroid negative feedback loop is working. The result is very high levels of circulating thyroid hormones and the negative feedback regulation will not work for the thyroid gland

The trigger for auto-antibody production is not known and there appears to be a genetic predisposition for Graves' disease.

Since Graves' disease is an autoimmune disease which appears suddenly, often quite late in life, a viral or bacterial infection may trigger antibodies which cross-react with the human TSH receptor.

There are really not many emergencies that we need to worry about regarding the thyroid gland - but is one of the rare exceptions. Thyroid storm is a medical emergency condition and needs to be treated immediately as it is a life-threatening condition. Symptoms that occur during a thyroid storm are more severe and result in the following complications:

 fever  dehydration  rapid heart rate  nausea/vomiting  diarrhea  irregular heart beat  weakness  heart failure  confusion/disorientation  death

Diagnosis

Graves' disease may present clinically with one of these characteristic signs:

 Exophthalmos (protuberance of one or both eyes)  Fatigue, weight loss with increased appetite, and other symptoms of hyperthyroidism  Rapid heart beat  Muscular weakness  Goitre

Another sign of Graves' disease is hyperthyroidism, i.e., overproduction of the thyroid hormones T3 and T4. Hyperthyroidism in Graves' disease is confirmed, as with any other cause of hyperthyroidism, by measuring elevated blood levels of free (unbound) T3 and T4.

Other useful laboratory measurements in Graves' disease include thyroid- stimulating hormone (TSH), usually low in Graves' disease due to negative feedback from the elevated T3 and T4. Thyroid-stimulating antibodies may also be detected.

Radioactive uptake test - iodine is needed by the human body to produce thyroxine (T4). This test measures the rate at which the thyroid gland takes up iodine by giving the patient a small amount of radioactive iodine and then measuring the level of it in the thyroid gland after a set period. If the uptake of radioactive iodine is high it means that the patient's thyroid gland is producing excessive amounts of thyroxine - this occurs in Graves' disease. In some other causes of hyperthyroidism the uptake of iodine is low.

Treatment

Treatment of Graves' disease includes anti-thyroid medications which reduces the production of thyroid hormone; radioactive iodine I-131 ; and (surgical removal of the thyroid gland). As operating on a hyperthyroid patient may be dangerous, prior to thyroidectomy pre-operative treatment with antithyroid drugs is given to render the patient "euthyroid" (i.e. normothyroid).

Treatment with anti-thyroid medications must be given for six months to two years to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. Anti-thyroid drugs block the binding of iodine and thus prevent thyroxine from being produced. These drugs can cause agranulocytosis, granulocytopenias as well as aplastic aneamia. Patients on these medications should see a doctor if they develop a sore throat. These drugs can cross the placenta and are secreted in breast milk and therefore should be used with caution in pregnancy and only when the benefits outweigh the risks.

Therapy with radioactive iodine is the most common treatment for Graves disease, and was developed in the early 1940s. This treatment is suitable for most patients. Radioactive iodine accumulates in the thyroid gland and irradiates the gland with its beta and gamma radiation. This treatment ablates (destroys) the thyroid gland and is normally a complication of this treatment. Patients need to be monitored frequently with thyroid blood tests to ensure that they are treated with thyroid hormones before they become symptomatically hypothyroid. Contradindications to this therapy is pregnancy as it may ablate the fetus’ thyroid gland. If this treatment is received the patient should not fall pregnant within 6 months of treatment date. This form of treatment may act slowly (over months to years) to destroy the thyroid gland and it does not work in all patients with some patients requiring second doses.

Surgery is suitable for young patients and pregnant patients. Indications are: a large goitre (especially when compressing the ), suspicious nodules or suspected cancer and patients with ophthalmopathy.

Advantages are immediate cure and potential removal of carcinoma. Its risks includes injury of the recurrent laryngeal nerve, hypoparathyroidism (due to removal of the parathyroid glands), hematoma (which can be life-threatening if it compresses the trachea), and scarring. After this treatment thyroid replacement pills to be taken for the rest of the patient's life.

β-blockers may be used to inhibit the sympathetic nervous system symptoms of tachycardia and nausea until such time as antithyroid treatments start to take effect

References: http://www.medicinenet.com/thyroid_storm_symptoms_causes_and_tre atment/views.htm http://en.wikipedia.org/wiki/Graves'_disease http://www.medicinenet.com/graves_disease/article.htm http://www.medicalnewstoday.com/articles/170005.php http://www.womenshealth.gov/publications/our-publications/fact- sheet/graves-disease.html