Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development and progression of thyroid tumors are associated with phenotype-specific mutations of genes involved in growth control. Thyroid cell growth is controlled in part by the interaction of TSH with its receptor, with subsequent activation of the GTP-binding protein and its effector, adenylyl cyclase. The resulting increase in intracellular cAMP stimulates growth in thyrocytes. The TSH receptor (TSH-R) is a seven-transmembrane domain receptor. Intracellular domains of the TSH-R important for signal transduction and which may serve as targets for mutational activation have been defined. In addition, mutations at specific loci of the alpha-subunit of G-protein in human thyroid tumors have been described. We examined 92 benign and malignant neoplastic thyroid tissues for possible mutations of the intracytoplasmic domains of the TSH-R known to be involved in signal transduction and for mutations within the hot spots of Gs alpha. Screening was carried out by single strand conformation polymorphism (TSH-R) or denaturing gradient gel electrophoresis (Gs alpha) of polymerase chain reaction-amplified tumor DNA. No mutations were observed in the cytoplasmic domains of the TSH-R, except for a neutral base substitution in codon 460 (GCG [Ala]-->GCA [Ala]) in 3 tumors, which was also present in constitutional DNA from the affected individuals. A heterozygous mutation of codon 201 of Gs alpha (GGT [Arg]-CAT [His]) was observed in a nodule from an adenomatous goiter. In addition, a codon 227 mutation (CAG [Glu]-CAT [His]) was identified in a follicular adenoma. We conclude that mutational activation of the intracytoplasmatic domains of the TSH-R is not a significant mechanism of thyroid tumorigenesis, whereas putative activating mutations within exons 8 and 9 of Gs alpha occur infrequently in some benign follicular tumors.
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PMID:The thyrotropin receptor (TSH-R) is not an oncogene for thyroid tumors: structural studies of the TSH-R and the alpha-subunit of Gs in human thyroid neoplasms. 850 Nov 49

Fever of unknown origin (FUO) refers to prolonged fevers of > or = 101 degrees F and that persists for > 3 weeks that remain undiagnosed after an intensive in-hospital/outpatient workup. The most common FUO categories of are infectious, neoplastic, rheumatic/inflammatory, and miscellaneous causes. Malignancies have supplanted infectious diseases as the most common cause of FUOs in the adult population. Rheumatic/inflammatory causes of FUO are relatively less common than previously because of the introduction over the years of sophisticated diagnostic tests for most rheumatic diseases. The rheumatic/inflammatory disorders that remain important causes of FUO today are those that cannot be readily diagnosed by readily available/noninvasive tests, for example, adult Still's disease and temporal arteritis (TA). In older patients with FUO, TA can be a difficult diagnosis when the characteristic findings (ie, scalp tenderness, jaw claudication) are not present. Patients with TA presenting as FUO often have only headaches that may be accompanied by bilateral jaw discomfort. Endocrine causes of FUOs are rare. The most common endocrine disorder rarely presenting as an FUO is de Quervain's subacute thyroiditis. As in TA, subacute thyroiditis may present with headache and pain at the angle of the jaw. Both TA and subacute thyroiditis may be accompanied by fatigue, weight loss, and night sweats. We present a case of 55-year-old woman who presented with an FUO with clinical and laboratory findings suggesting TA. However, the absence of thrombocytosis and a normal alkaline phosphatase argued against the diagnosis of TA. Also against the diagnosis of TA was weight loss without loss of appetite and a slightly increased pulse. After nonspecific laboratory test results suggested that TA was not the cause of her FUO, additional tests were ordered. Thyroid function test results suggested the possibility of de Quervain's subacute thyroiditis as the cause of her FUO. To the best of our knowledge, this is the first case of de Quervain's subacute thyroiditis presenting as an FUO with elevated ferritin levels.
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PMID:Fever of unknown origin (FUO): de Quervain's subacute thyroiditis with highly elevated ferritin levels mimicking temporal arteritis (TA). 2010 88