Diagnosis
The onset of Graves' disease symptoms is often insidious; the intensity of symptoms can increase gradually for a long time before the patient is correctly diagnosed with Graves’ disease, which may take months or years. (Not only Graves' disease, but most endocrinological diseases also have insidious, subclinical onsets.) One study puts the average time for diagnosis at 2.9 years, having observed a range from three months to 20 years in their sample population. A 1996 study offers a partial explanation for this generally late diagnosis, suggesting the psychiatric symptoms cause delays in seeking treatment, as well as delays in receiving appropriate diagnosis. Also, earlier symptoms of nervousness, hyperactivity, and a decline in school performance, may easily be attributed to other causes. Many symptoms may occasionally be noted, at times, in otherwise healthy individuals who do not have thyroid disease (e.g., everyone feels anxiety and tension to some degree), and many thyroid symptoms are similar to those of other diseases. Thus, clinical findings may be full-blown and unmistakable or insidious and easily confused with other disorders. The results of overlooking the thyroid can, however, be very serious. Also noteworthy and problematic, in a 1996 survey, study respondents reported a significant decline in memory, attention, planning, and overall productivity from the period two years prior to Graves' symptoms onset. Also, hypersensitivity of the central nervous system to low-grade hyperthyroidism can result in an anxiety disorder before other Graves’ disease symptoms emerge. Panic disorder, for example, has been reported to precede Graves’ hyperthyroidism by four to five years in some cases, although it is not known how frequently this occurs.
The hyperthyroidism from Graves' disease causes a wide variety of symptoms. The two signs are truly 'diagnostic' of Graves' disease (i.e., not seen in other hyperthyroid conditions), exophthalmos (protuberance of one or both eyes) and pretibial myxedema, a rare skin disorder with an occurrence rate of 1-4%, that causes lumpy, reddish skin on the lower legs. Graves' disease also causes goitre (a diffuse enlargement of the thyroid gland). Though it also occurs with other causes of hyperthyroidism, Graves' disease is the most common cause of diffuse goitre. A large goitre is visible to the naked eye, but a smaller goitre may be detectable only by a physical exam. On occasion, goitre is not clinically detectable, but may be seen only with CT or ultrasound examination of the thyroid.
A highly suggestive symptom of hyperthyroidism, is a change in reaction to external temperature. A hyperthyroid person will usually develop a preference for cold weather, a desire for less clothing and less bed covering, and a decreased ability to tolerate hot weather. When thyroid disease runs in the family, the physician should be particularly wary; studies of twins suggest genetic factors account for 79% of the liability to the development of Graves’ disease (whereas environmental factors presumably account for the remainder). Other, nearly pathognomonic signs of hyperthyroidism are excessive sweating, high pulse during sleep, and a pattern of weight loss with increased appetite (although this may also occur in diabetes mellitus and malabsorption or intestinal parasitism).
Hyperthyroidism in Graves' disease is confirmed, as with any other cause of hyperthyroidism, by a blood test. Elevated blood levels of the principal thyroid hormones (i.e. free T3 and T4), and a suppressed thyroid-stimulating hormone (low due to negative feedback from the elevated T3 and T4), point to hyperthyroidism. However, diagnosis depends to a considerable extent on the position of the patient’s unique set point for T4 and T3 within the laboratory reference range (an important issue that is further elaborated below).
Differentiating Graves' hyperthyroidism from the other causes (thyroiditis, toxic multinodular goiter, toxic thyroid nodule, and excess thyroid hormone supplementation) is important to determine proper treatment. Thus, when hyperthyroidism is confirmed, or when blood results are inconclusive, thyroid antibodies should be measured (almost all patients with Graves' hyperthyroidism have detectable TSHR-Ab levels). Measurement of thyroid-stimulating immunoglobulin (TSI) is the most accurate measure of thyroid antibodies. They will be positive in 60 to 90% of children with Graves' disease. If TSI is not elevated, then a radioactive iodine uptake should be performed; an elevated result with a diffuse pattern is typical of Graves' disease. Biopsy to obtain histological testing is not normally required, but may be obtained if thyroidectomy is performed.
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