[Treatment of thyroiditis].
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Biomedical subjects
Publications and source records attributed to Csaba Balázs.
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Lingual thyroid is a rare embryological aberration with incidence of 1:100,000. It is an ectopic thyroid tissue. In most cases, it is diagnosed in childhood and young adulthood but frequently around menopause. It appears as a mass on the base of the tongue causing mostly local symptoms often with hypothyroidism, rarely with thrive and mental retardation. Authors describe the features, diagnosis and therapy of lingual thyroid with the case of a 23-year-old woman. They analyze the probable pathomechanism and potential risk of malignant transformation of lingual thyroid. In this case, the diagnosis was described at the age of 17, but therapy or further investigation did not take place then. Six years later the patient visited our surgery with local complaints in euthyroid phase. Since the suppression therapy proved to be unsuccessful, the problem was finally solved by operation.
It has been observed in the past few years, that radioiodine therapy triggers autoimmune thyrotoxicosis. The possible mechanism of this phenomenon is that protein fragments enter the circulation after thyroid cell damage induced by radiation. TSH-receptor autoantibodies are produced in genetically susceptible patients after radiotherapy. In treating nodular goiter--a non-immune thyroid disease--with 131I, an immunogenic disorder--Basedow-Graves' disease--may develop. The authors present this phenomenon in a case of a 67 year-old woman with a history of operation for euthyroid nodular goiter in 1977. In November 2001, she was admitted to the hospital with local signs and symptoms of relapse of euthyroid nodular goiter (TSH-receptor antibodies were not detected). She was treated with oral doses of 320 MBq of radioiodine to reduce the thyroid volume. Four months after radioiodine therapy the patient had developed signs of thyrotoxicosis. At that time TSH-receptor antibodies were found to be positive. Thyreostatic therapy was administered and still being in use till today. The authors draw the attention to the fact that, when a hyperthyrosis develops after radioiodine therapy of a non-immune thyroid disease, the possibility of Graves-Basedow disease should be raised, especially in a patient with a positive family history.
The rapidly escalating number of genome sequences has emphasized the basic tenants of the schema of life. By the same token comparisons according to specialized function or niche within nature expose genomic strategies to optimize the use of resources and ensure biological success. Increasing complexity may result from diversification, shuffling, and re-arrangement of an otherwise limited functional genomic complement. To further test the concept of relative structural plasticity of the TSH receptor we sequenced the TSHR gene of two Old World monkey species Macaca mulatta and Cercopithecus aethiops, evolutionary removed from Homo sapiens by >20Myr. Both genes encoded a protein of 764 residues. This structure was 99% homologous between the two species of Old World monkeys while C. aethiops was 97% and M. mulatta was 96% homologous to H. sapiens. TSHR sequence comparisons were sought for an additional eight mammals as well as four (two Salmon, Tilapia, and Sea Bass) from teleosts. The amino-acid sequences of the 14 TSH receptors were similar. The most variable sequences were those of the intracellular tail and the distal cysteine-rich C-terminus flanking region of the ectodomain, whereas the trans-membrane domain was most preserved. Some sequences were decidedly H. sapiens specific, while others were primate specific or showed the changes expected of evolutionary descent. Others, however, exhibited "cross-species polymorphism," sometimes at quite remarkable evolutionary distances. As opposed to H. sapiens the sequence differences may have subtle influences on TSHR function or may affect long-range compensation for radical changes in adducts. The two Old World monkeys share with other lower mammals the absence of a glycosylation site at 113-115. Sea Bass and Tilapia have four glycosylation sites, whereas the two salmon receptors have only three. Changes in some critical residues raise questions about variation in function: thus S281 is conserved in all mammals and an important determinant of negative agonist function of TSHR is replaced by R in Sea Bass. Likewise the K183, found at an important transitional region at LRR 6 conserved in all mammals, is represented by M in fish and may contribute to TSHR lutenization in fish. There is no evidence that evolutionary changes in primate receptors are more rapid than that in other mammals and the separation times of different mammals based on silent nucleotide changes of TSHR are closely parallel to archaeological estimates. Results of correlated mutation analysis, referenced to the rhodopsin crystal structure, affirms dimerization of TSHR transmembrane helices. In addition, it suggests the involvement of critical lipid-facing residues in the helices in receptor dimerization and oligomerization. We highlight the value of evolutionary informatics and set the stage for dissecting out potential subtle differences in TSHR function associated with structural variations.
The effects of tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6) and interferon gamma (IFNgamma) were studied on the activity of type 2,5'-deiodinase and on the binding of [125I] T(4) to proteins in human thyroid cytosolic (supernatant) and membrane (pellet) fractions. The activity of thyroid type 2,5'-deiodinase was measured by iodothyronine outer ring deiodinase assay. The binding of [125I] T(4) to the proteins of thyroid cytosolic and membrane fractions was determined by autoradiography. The results showed that thyroid type 2,5'-deiodinase activity could be detected also in the cytosolic fraction, not only in the membrane. TNFalpha, IL-6 and IFNgamma could inhibit the type 2 deiodinase activity in vitro. The dose-dependent binding of [125I] T(4) to the proteins of 29, 66 and 200 kDa could be observed both in the cytosolic and membrane fractions. TNFalpha and IFNgamma inhibited the binding of [125I] T(4) to the two characteristic proteins of type 2,5'-deiodinase, to proteins of 29 and/or 200 kDa, both in the cytosolic and membrane fractions. We conclude that TNFalpha, IL-6 and IFNgamma can inhibit the activity of type 2,5'-deiodinase. Furthermore, TNFalpha and IFNgamma can still also decrease the binding of [125I] T(4) to the enzyme in vitro. It can be suggested that the increased level of these cytokines can be one of the reasons in the induction of the clinical symptoms in nonthyroidal illness associated with low levels of T(3).
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