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Graves' Disease                 

Graves' Disease (Toxic diffuse goiter)      See   hyperthyroidism              REF:  Ferri's Clinical Advisor: Instant DX and RX, 8th ed. 2006

Graves’ disease is a hypermetabolic state characterized by thyrotoxicosis, diffuse goiter, and infiltrative ophthalmopathy (edema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat); infiltrative dermopathy characterized by lymphocytic infiltration of the dermis, accumulation of glycosaminoglycans, and edema is occasionally present.

Graves' disease is most likely an autoimmune disorder with B lymphocytes producing immunoglobulins, some of which bind to and activate the TSH receptor, stimulating excess thyroid growth and hormone secretion. For these antibodies, the TSH receptor appears to represent the antigenic site, and they act like TSH and are termed thyroid-stimulating immunoglobulins (TSI). Other antibodies occur in Graves' and other autoimmune diseases such as Hashimoto's disease. These antibodies bind to the TSH receptor but stimulate only thyroid growth without increasing thyroid hormone secretion.   The thyroid gland in Graves' disease enlarges diffusely and contains increased vascularity. The parenchyma exhibits hypertrophy and hyperplasia, with follicular cells showing increased height, surrounding a lumen containing a decreased amount of colloid. Infiltration by lymphocytes indicates the autoimmune nature of the disease.



  • Tachycardia, palpitations, tremor, hyperreflexia
  • Goiter, exophthalmos (50% of patients), lid retraction, lid lag
    A hallmark finding of Graves' disease is infiltrative ophthalmopathy. Clinically detectable eye disease occurs in 20 to 40% of patients with Graves' disease, but severe ophthalmopathy requiring aggressive treatment affects only about 5%. Affected persons complain of easy tearing, photophobia, a feeling of sand in the eyes, diplopia, and decreased visual acuity. Ophthalmopathy affects the anterior soft tissue structures of the eye and with progressive severity involves more posterior structures as well. Periorbital edema and chemosis occur early and result from impaired drainage of the orbital veins. The swollen and fibrotic muscles cause lid retraction and restrict ocular movement, leading to diplopia. Upward gaze is most frequently impaired; with limitations of lateral gaze occurring less frequently.
  • Increased sweating, brittle nails, clubbing of fingers
  • Nervousness, weight loss, heat intolerance, and may have atrial fibrillation
  • Localized dermopathy (1% to 2% of patients) is most frequent over the anterolateral aspects of the skin but can be found at other sites (especially after trauma)



  • Decreased TSH;  Increased free thyroxine (T4) and free triiodothyronine (T3)
    In some patients, however, the marked stimulation of TSH receptors leads to higher hormone production rates of T3 so that serum T3 levels rise markedly whereas T4 levels remain normal. This combination of laboratory values is termed T3 toxicosis and is most frequently found during the initial phases or a relapse of Graves' disease. TSH levels are undetectable and serve to exclude TSH-producing tumors or thyroid hormone resistance as causes for the elevated thyroid hormone levels.
  • Presence of thyroid autoantibodies (useful in selected patients to differentiate Graves’ disease from toxic nodular goiter)


  • 24-hr radioactive iodine uptake (RAIU): increased homogeneous uptake
  • CT or MRI of the orbits is useful if there is uncertainty about the cause of ophthalmopathy


Treatment of Graves' Disease

See Rx of Hyperthyroidism