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Pathophysiology

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  • over 90% of patients have TSH receptor antibodies which stimulate the thyroid cell - these are known as thyroid stimulating immunoglobulins or TSI, and correlate with the degree of hyperthyroidism

  • a second set of TSH receptor antibodies stimulate thyroid growth - but not hormone production. These thyroid growth-stimulating immunoglobulins (TGI's) determine the degree of thyroid enlargement, if any. TGI's may occur also in other toxic and non-toxic goitre

  • eye involvement may be the result of an independent ophthalmic immunoglobulin against the eye muscle basement cell membrane. Ophthalmic Graves' disease may exhibit all the features of Graves' ophthalmopathy yet the patient is euthyroid. Alternatively, autoantibody against the TSH receptor on retrobulbar fibroblasts may be the source of ophthalmic manifestations

  • in some cases patients with Graves' disease produce antithyroid peroxidase (previously known as antimicrosomal antibodies) in addition to TSI, and about 5% of patients will become hypothyroid spontaneously with time

  • the clinical spectrum of Graves' disease is made more complex by the rare occurrence of patients who secrete antibodies that either lead to stimulation of the TSH receptor (TSI) or result in the blocking of the TSH receptor. Therefore, depending on the activity of the stimulating and blocking antibodies the clinical condition ranges from hyperthyroidism to euthyroidism, to hypothyroidism and recurrent hyperthyroidism

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