The TSH receptor and its role in thyroid disease |
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Authors: | Kopp P |
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Institution: | (1) Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Tarry 15, 303 East Chicago Avenue, Chicago, Illinois 60611 (USA), Fax +1 312 908 9032, e-mail: p-kopp@northwestern.edu, US |
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Abstract: | The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and disease. TSH, acting through the TSH receptor,
is the major stimulator of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the
target of stimulating antibodies that cause hyperthyroidism. Although still a topic of debate, the TSH receptor has been implicated
in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor
are involved in the development of hypothyroidism in a subset of patients with autoimmune hypothyroidism. Transplacental passage
of stimulating or blocking TSH receptor antibodies from a mother with autoimmune thyroid disease may result in transient hyper-
or hypothyroidism in early infancy. During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational
hyperthyroidism through cross-reaction with the TSH receptor. Gestational hyperthyroidism may also be involved in the pathogenesis
of hyperemesis gravidarum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations
of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the germline
give rise to nonautoimmune familial hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function mutations
are dominant, and one mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor
alleles lead to variable degrees of resistance to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropinemia
to overt hypothyroidism with thyroid hypoplasia.
Received 31 January 2001; received after revision 3 April 2001; accepted 3 April 2001 |
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Keywords: | , Thyroid, thyrotropin, receptor, cAMP, hyperthyroidism, hypothyroidism, autoimmune thyroid disease, mutation, |
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