Most of us now call the disorder Graves' disease, but after reading Basedow's Syndrome or Disease you may feel that Irish physician Robert James Graves (1796-1853) was a little fortunate in having his name widely associated with the condition in preference to a number of other potential claimants. Take for example English doctor Caleb Hillier Parry (1755-1822) or German physician Karl Adolph von Basedow (1799-1854) - after whom the disease is more commonly known on the Continent; just two of perhaps half a dozen who played some part in describing the disorder we now accept as Graves' disease. Read these articles and others at the splendid Who Named It? and decide for yourself.

Graves' disease, described in one reference as 'a host defence mechanism gone awry', is the most frequent diagnosis underlying the development of hyperthyroidism (overproduction of thyroid hormones) in North America where it is also the commonest autoimmune disease affecting up to 2% of the population. The disease runs a chronic course characterised by phases of exacerbation and remission, each of unpredictable onset and duration. It can occur at any age and in either sex, but most frequently strikes women in the middle decades - figures from the Thyroid Foundation of America disclosing that in the US it affects women ten times more often than men. And while 3.5 million women over the age of 15 are estimated to be receiving treatment, an alarming 550,000 are thought to be undiagnosed.

Barbara Bush, wife of ex-President George Bush, became a high profile Graves' disease statistic in 1989, only for her husband to contract the disease 18 months later. The odds of both spouses developing the same autoimmune condition are estimated at more than one in 10,000, increasing to a remarkable one in 3 million of it happening within a period of 2 years. Read the full story at Graves' Disease - the Heart of the Matter and then click on Rebecca Blatt's My Graves' Disease Timeline for a graphic first-hand personal account of her frustrations in obtaining a correct diagnosis and her tribulations during treatment.

The term 'Graves' disease' tells us nothing about its nature, but one of its synonyms - diffuse toxic goitre - is very descriptive: 'diffuse' because the entire thyroid gland is involved; 'toxic' because the patient often appears hot and flushed, as if he or she were 'toxic' due to infection; and 'goitre' meaning enlargement of the thyroid gland. Thyroid hormones have a wide variety of effects on the body that are reflected in the symptoms and signs of Graves' disease that include feelings of anxiety, shortness of breath, loss of energy, heat intolerance, tremor, rapid pulse, difficulty with sleeping, abnormally frequent bowel movements, menstrual irregularities, muscle weakness or wasting, weight loss despite a normal or increased appetite, and warm moist skin. Eye complications affect almost 50% of all people with Graves' disease, but the changes, such as dryness and irritation, are often slight. At the other end of the scale 3-5% of cases require intensive treatment or surgical intervention, many exhibiting exophthalmus - the classic protrusion of the eyeballs caused by swollen tissue behind the eye - often with red swollen lids (see photograph at Development of the Clinical Picture and the Course of the Disease) . Other patients may develop pretibial myxoedema - a lumpy thickening of the skin in front of the shins. To see a picture of a patient with this condition go to The Thyroid and its Diseases, click The Skin on the left-hand menu and scroll down the main frame.

So what's happening to the thyroid gland in Graves' disease? Make a start by going first to How Your Thyroid Works which provides a simple illustrated introduction of the process whereby iodine is converted into two thyroid hormones - thyroxine (T4) and triiodothyronine (T3) - that influence our metabolism. The role of the pituitary gland in this process is neatly analogised. If you find this a bit tame, try Thyroid Gland and then take your pick from the impressive menu in the left-hand frame. In Graves' disease cells of the immune system attack the thyroid gland stimulating it to overproduce thyroid hormones resulting in hyperthyroidism, sometimes likened to the body's chemistry being in overdrive.

Graves' disease is generally accepted as a disease syndrome induced by autoimmunity to the thyroid, but the key question is 'why?'. It's not known exactly what sets Graves' disease going other than disordered immunity, but it's generally thought to be due to a combination of environmental and genetic factors influencing the autoimmune response. Causes of Graves' Disease provides more details.

While the classical clinical signs of Graves' disease are easily recognised by the practitioner, diagnostic tests can confirm both obvious and more subtle disease states. And now that you've acquired an understanding of the basics, you'll find it easier to digest Diagnosing Graves' Disease.

Rest and sedation were the only treatment options available for hyperthyroidism until the 1880s when a patient was cured by having part of the thyroid gland surgically removed. In the early days of surgery, however, patients were often so ill with the condition that many died during their operation. Not until the 1920s, when doctors learned to control the severity of hyperthyroidism before the operation by giving patients iodine drops, did the risk of surgery markedly decrease, and for a while physicians tended to treat patients with iodine alone. Although this worked temporarily, control of the disease was unpredictable and many patients suffered relapses. Nowadays, fortunately, Graves' disease is an entirely treatable condition with currently three major approaches: antithyroid drugs; radioactive iodine; and surgery. For a one-page summary of the three options go to Current Treatment of Graves' Disease and for a list of their respective advantages and disadvantages continue to Dis/Advantages of Various Treatment Modalities.

Few antithyroid drugs are available: carbimazole - the most commonly prescribed antithyroid drug in the UK and used primarily in Europe and Asia; methimazole, to which carbimazole is completely metabolised, is a standard treatment in the US; and propylthiouracil (PTU), dominate this sector. All have been in use for more than 50 years and act essentially by interfering with the synthesis of thyroid hormones. For a UK perspective on antithyroid drugs, click on BNF 42, enter 'antithyroid' in the 'Full Text' box, hit 'Go' and then click '6.2.2 Antithyroid drugs' in the list of Search results that appears underneath. A comparable US site that's more easily accessible is Medications Used for the Treatment of Hyperthyroidism. On the second page of this article note the reference and rationale to the use of beta-blockers.

Radioactive iodine was first used to treat a patient in 1941 and the form now universally employed (I-131) has been available for 40 years. Administered as a capsule or with water, radioactive iodine is taken up by the thyroid gland where it irradiates, and hence destroys, thyroid tissue. Treatments of Graves' Disease: Radioactive Iodine tells you all you need to know.

When surgery is chosen as the preferred method of treatment, it usually involves a subtotal thyroidectomy performed under general anaesthesia. Click on Surgery for a summary of the indications for surgery, preparation, outcome, and postoperative complications and care.

Treatment options in Graves' disease are less than ideal, but have undergone little fundamental change over many decades. Patients will anticipate with some optimism that the initiatives described in Future Direction for Research will yield a greater understanding of the disease's precise mechanism and genetic and environmental factors underlying its onset and progression, and ultimately improved treatments.

Do you have any comments on this article? Please contact Geoff directly at geoff@healthcare-edit.demon.co.uk.

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