Graves-Basedow disease
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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), or with radioactive iodine if refractory.
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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 (difficulting rising from a chair or squatting position) and hyperactive deep tendon reflexes
- Gastrointestinal: diarrhoea (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 (T4) and thyroid-stimulating hormone (TSH) are determined in the medical laboratory. T4 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.
Treatment
Medical treatment of Graves disease includes antithyroid drugs, radioactive iodine and surgery.
Antithyroid drugs
The main antithyroid drugs are methimazole (US), carbimazole (UK) and propylthiouracil (PTU). These drugs block the binding of ioding and coupling of iodotyrosines. The most dangerous side-effect is agranulocytosis (1/250, more in PTU); this is an idiosyncratic reaction which does not stop on cessation of drug). Others include granulocytopenia (dose dependant, which improves on cessation of the drug) and aplastic anemia. Patients on these medications should stop the medication and see a doctor if they develop sore throat or fever. The commonest side effects are rash and peripheral neuritis. These drugs also cross the placenta and are secreted in breast milk.
Radioiodine
This modality is suitable for older patients. Indications for radioiodine are: failed medical therapy or surgery and where medical or surgical therapy are contraindicated.
Contraindications to RAI are pregnancy, ophthalmopathy (it can aggravate thyroid eye disease), solitary nodules and young patients. Disadvantages of this treatment are a high incidence of hypothyroidism (up to 80%) requiring hormone suppletion. It acts slowly and has a high relapse rate.
Surgery
This modality is suitable for young patients and pregnant patients. Indications are: a large goitre (especially when compressing the trachea), suspicious nodules or suspected cancer (to pathologically examine the thyroid) and patients with opthalmopathy.
Both bilateral subtotal thyroidectomy and the Hartley-Dunhill procedure (hemithyroidectomy on 1 side and partial lobectomy on other side) are possible.
Advantages are: immediate cure and potential removal of carcinoma. Its risks are 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.
Eye disease
- For mild disease - artificial tears, steroid eyedrops, oral steroids (to reducechemosis)
- For moderate disease - lateral tarsorrhaphy
- For severe disease - orbital decompression or retro-orbital radiation
If left untreated
If left untreated, more serious complications could result, including birth defects in pregnancy, increased risk of a miscarriage, and in extreme cases, death. Graves-Basedow disease is often accompanied by an increase in heart rate, which may lead to further heart complications.
Epidemiology
There is female predominance (ratio 8:1), and onset is commonly in the third to fifth decades of life. There is a marked family preponderance, which has led to speculation that there may be a genetic cause. To date, no clear genetic defect has been found that would point at a monogenic cause.
History
Ljunggren (1983) suggests that the Persian physician Sayyid Ismail Al-Jurjani should be credited with recognising the disease, having noted the association of goitre and exophthalmos, in "Thesaurus of the Shah of Khwarazm", the most famous of his five books, and the major medical dictionary of its time.
Caleb Hillier Parry (1755-1822) first noted the clinical picture in 1786, and it is reported in his posthumous collection of unpublished writings in 1825. It was also described by the Italians Giuseppe Flajani (1741-1808) in 1802 and Antonio Giuseppe Testa (1756-1814) in 1810. Robert James Graves (1797-1853) of Ireland in 1835, and Karl Adolph von Basedow in 1840, independently reported the constellation of symptoms. On the European Continent the term Basedow's disease is the more common, while it is known as Graves' disease in the English-speaking world.
Bibliography
- Sayyid Ismail Al-Jurjani. Thesaurus of the Shah of Khwarazm.
- Flajani G. Sopra un tumor freddo nell'anterior parte del collo broncocele. (Osservazione LXVII). In Collezione d'osservazioni e reflessioni di chirurgia. Rome, Michele A Ripa Presso Lino Contedini, 1802;3:270-273.
- Testa AG. Delle malattie del cuore, loro cagioni, specie, segni e cura. Bologna, 1810. 2nd edition in 3 volumes, Florence, 1823; Milano 1831; German translation, Halle, 1813.
- Parry CH. Enlargement of the thyroid gland in connection with enlargement or palpitations of the heart. Posthumous, in: Collections from the unpublished medical writings of C. H. Parry. London, 1825, pp. 111-129. According to Garrison, Parry first noted the condition in 1786. He briefly reported it in his Elements of Pathology and Therapeutics, 1815. Reprinted in Medical Classics, 1940, 5: 8-30.
- Graves RJ. New observed affection of the thyroid gland in females.(Clinical lectures.) London Medical and Surgical Journal (Renshaw), 1835; 7: 516-517. Reprinted in Medical Classics, 1940;5:33-36.
- Marsh H. Dilatation of the cavities of the heart. Enlargement of the thyroid gland. Dublin Journal of Medical and Chemical Science. 1842, 20: 471-474. Abstract.
- Von Basedow KA. Exophthalmus durch Hypertrophie des Zellgewebes in der Augenhöhle. [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1840, 6: 197-204; 220-228. Partial English translation in: Ralph Hermon Major (1884-1970): Classic Descriptions of Disease. Springfield, C. C. Thomas, 1932. 2nd edition, 1939; 3rd editon, 1945.
- Von Basedow KA. Die Glotzaugen. [Casper's] Wochenschrift für die gesammte Heilkunde, Berlin, 1848: 769-777.
- Begbie J. Anaemia and its consequences; enlargement of the thyroid gland and eyeballs. Anaemia and goitre, are they related? Monthly Journal of Medical Science, London, 1849, 9: 496-508.
External link
- Template:OMIM
- Whonamedit.com (http://www.whonamedit.com/synd.cfm/1517.html) on the history and naming of the diseasede:Morbus Basedow