| Disease Associations |
Note=Defects in TSHR are found in patients affected by hyperthyroidism with different etiologies. Somatic, constitutively activating TSHR mutations and/or constitutively activating G(s)alpha mutations have been identified in toxic thyroid nodules (TTNs) that are the predominant cause of hyperthyroidism in iodine deficient areas. These mutations lead to TSH independent activation of the cAMP cascade resulting in thyroid growth and hormone production. TSHR mutations are found in autonomously functioning thyroid nodules (AFTN), toxic multinodular goiter (TMNG) and hyperfunctioning thyroid adenomas (HTA). TMNG encompasses a spectrum of different clinical entities, ranging from a single hyperfunctioning nodule within an enlarged thyroid, to multiple hyperfunctioning areas scattered throughout the gland. HTA are discrete encapsulated neoplasms characterized by TSH- independent autonomous growth, hypersecretion of thyroid hormones, and TSH suppression. Defects in TSHR are also a cause of thyroid neoplasms (papillary and follicular cancers).Note=Autoantibodies against TSHR are directly responsible for the pathogenesis and hyperthyroidism of Graves disease. Antibody interaction with TSHR results in an uncontrolled receptor stimulation.Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) [MIM:275200]: A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. {ECO:0000269PubMed:10720030, ECO:0000269PubMed:11095460, ECO:0000269PubMed:11442002, ECO:0000269PubMed:12050212, ECO:0000269PubMed:14725684, ECO:0000269PubMed:15531543, ECO:0000269PubMed:7528344, ECO:0000269PubMed:8954020, ECO:0000269PubMed:9100579, ECO:0000269PubMed:9185526, ECO:0000269PubMed:9329388}. Note=The disease is caused by mutations affecting the gene represented in this entry.Familial gestational hyperthyroidism (HTFG) [MIM:603373]: A condition characterized by abnormally high levels of serum thyroid hormones occurring during early pregnancy. {ECO:0000269PubMed:9854118}. Note=The disease is caused by mutations affecting the gene represented in this entry.Hyperthyroidism, non-autoimmune (HTNA) [MIM:609152]: A condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent. {ECO:0000269PubMed:10199795, ECO:0000269PubMed:10852462, ECO:0000269PubMed:11081252, ECO:0000269PubMed:11127522, ECO:0000269PubMed:11201847, ECO:0000269PubMed:11517004, ECO:0000269PubMed:11549687, ECO:0000269PubMed:15163335, ECO:0000269PubMed:7800007, ECO:0000269PubMed:7920658, ECO:0000269PubMed:8636266, ECO:0000269PubMed:8964822, ECO:0000269PubMed:9349581, ECO:0000269PubMed:9360555, ECO:0000269PubMed:9398746, ECO:0000269PubMed:9589634}. Note=The disease is caused by mutations affecting the gene represented in this entry.
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Version 5.4
