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The diagnosis of Graves' disease (GD) is based on clinical and biochemical evidence of hyperthyroidism. Diagnostic testing for Graves' disease generally consists of three parts:

• Physical examination
• Laboratory evaluation
• Imaging studies

Physical Examination

The health care provider will assess the following during a thorough physical examination:

• Thyroid gland - to assess enlargement in size by palpating the gland.

• Blood vessels around the thyroid gland, which are often dilated. The doctor may also listen to certain blood vessels with a stethoscope to determine if there is a bruit (abnormal sound) due to increased blood flow.

• Skin - may be warm and velvety

• Hair - may be soft and fine

• Nails - may be soft and separating from underlying tissue

• Eyes - may be irritated or protruding or may have a characteristic 'fixed stare' appearance

• Blood pressure and pulse

• Resting heart rate

• Signs of fine tremor

• Weight loss

• Shortness of breath

• Family history of:

  • thyroid disease
  • prematurely gray hair (in the 20's)
  • autoimmune diseases such as juvenile diabetes or pernicious anemia

Following a diagnosis of Graves' disease, the doctor may want to examine other members of the immediate family to evaluate if anyone else exhibits symptoms of thyroid disease.

Older patients with Graves' disease may have subtle symptoms for a long time, (e.g., smaller goiters than may be expected and no ocular symptoms) which can make the diagnosis of Graves' disease more difficult. Elderly patients may also present with cardiovascular symptoms only, such as atrial fibrillation or sudden onset of angina (chest pain).

Laboratory Evaluation of Graves' Disease

In order to evaluate thyroid function, a blood test is required and the following parameters are measured:

• TSH (thyroid stimulating hormone) - usually low or undetectable.
• Total T4 or free T4 - to determine thyroid function. Free T4 is a newer test than the total T4 and is considered by many to be a more accurate reflection of thyroid hormone function than total T4. Elevated levels of T4 typically represent an overactive thyroid gland
• T3 - to help determine the severity of the hyperthyroidism
• Complete blood count (may be checked prior to initiating anti-thyroid medications)

Most patients with Graves' disease have elevated T3 and T4 levels while TSH is low or undetectable. However, laboratory results must be looked at together with the clinical assessment since values of each of these tests can vary.

When the diagnosis of Graves' disease is inconclusive, the doctor may order two additional tests:

• Thyroid-peroxidase antibodies (TPA) which are high in approximately 75% of Graves' disease patients. TPA is a marker of thyroid autoimmune activity.

• Thyroid stimulating immunoglobulins (TSH receptor antibodies)

Since Graves' disease is an autoimmune disorder, patients may have elevated levels of circulating antibodies, (e.g., thyroid peroxidase antibodies, TSH receptor antibodies). For initial diagnosis, however, there are differing opinions as to whether it is important to measure these antibodies.

If symptoms of Graves' ophthalmopathy are present and blood tests for Graves' disease are positive there is usually no need for further testing to confirm a diagnosis.

Imaging Studies for Graves' Disease

• Radioactive Iodine Uptake (RAIU) - RAIU shows areas of increased or decreased functioning of the thyroid gland by measuring the amount of radioactive iodine absorbed within the thyroid gland. RAIU also images nodules (masses) which may appear on the thyroid gland and indicates whether the nodule is active ("hot") or not ("cold"). The patient ingests radioactive iodine (I-123 or I-131) in liquid or capsule form and returns later (usually 6 and 24-hours later) to have the radioactivity measured. A gamma probe measures the amount of radioactivity in the thyroid gland and that measurement is compared to the original dose of radioactivity that was administered. The result is reported as a percent of the original dose. A high radioactive uptake is typically characteristic of Graves' disease. A low uptake may point to a viral infection or other inflammatory condition of the thyroid gland.