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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Resistance to thyroid hormone--an uncommon cause of thyroxine excess and inappropriate TSH secretion.

Resistance to thyroid hormone (RTH) is an uncommon inherited cause of hyperthyroxinemia with inappropriate TSH secretion. The syndromes are characterized by reduced target tissue responsiveness to circulating free thyroid hormones. The differential diagnosis to other diseases with similar laboratory results (high T4 with normal TSH) like familial dysalbuminemia or antibodies against iodothyronines or TSH is now possible with the appropriate use of new assays for free thyroid hormones. In the presence of thyrotoxic symptoms it may be difficult to differentiate the syndrome from a TSH-secreting pituitary tumour. Familial occurrence and a normal TSH-response to TRH that can not be suppressed by T3 are characteristic features of RTH, that may be helpful in that respect. The majority of RTH cases are dominantly inherited and have highly variable clinical signs and symptoms. There are, however, mainly two forms of the syndrome that have been shown to overlap clinically and biochemically, namely a generalised resistance (GRTH) and a more "selective" pituitary resistance to thyroid hormones (PRTH). The absence of thyrotoxic symptoms rather suggests GRTH, whereas thyrotoxic signs seem to be characteristic for PRTH. Following the cloning of thyroid hormone receptors, familial GRTH was shown to be tightly linked to the TR-(Thyroid hormone receptor)-beta gene locus. Molecular genetic studies have shown that even within a single kindred the same receptor mutation was associated with both, GRTH or PRTH, and therefore suggest that these two forms represent part of a variable clinical spectrum of a single genetic disorder.(ABSTRACT TRUNCATED AT 250 WORDS)[1]


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