The discovery in 1956 of the long-acting thyroid stimulator of Graves' disease, now known as thyroid-stimulating antibodies, was seminal. A new mechanism for disease was revealed that appears applicable to virtually all endocrine systems, involving the growth as well as the function of endocrine cells. An endocrine gland may fail through at least three autoimmune mechanisms: destruction, atrophy, and inhibition of function. Destruction is probably irreversible but is not usually distinguishable clinically from receptor blockade causing atrophy or from metabolic unresponsiveness. The contribution made by receptor autoimmunity to endocrine diseases other than thyroid disease is at present unclear, but with immunologic manipulation it is potentially reversible, improving the replicative capacity of the gland, its metabolic responsiveness, or both.

DOI: 10.1056/NEJM199011083231906
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