Thyrotropin Receptor Mutations and Thyroid Hyperfunctioning Adenomas Ten Years After Their First Discovery: Unresolved Questions

Dipartimento di Medicina Sperimentale e Clinica, University of Catanzaro, Catanzaro, Italy.
Thyroid (Impact Factor: 4.49). 05/2003; 13(4):341-3. DOI: 10.1089/105072503321669811
Source: PubMed


Ten years after the first description of activating mutations in the thyroid stimulating hormone receptor (TSHR) gene in sporadic autonomous hyperfunctioning thyroid adenomas, there is general agreement in assigning a major pathogenic role of this genetic abnormality, acting via the constitutive activation of the cAMP pathway, in both the growth and functional characteristic of these tumours. From the beginning, however, the pathophysiological and clinical relevance of somatic TSHR mutations has been debated and some arguments still exist against a fully causative role of these mutations and the practical value of detecting these mutations for the diagnosis, treatment and prognosis of thyroid hot nodules. Some major issues will be examined herein, including (a) the frequency of TSHR alterations in various reports showing that the genetic abnormality underlying the pathogenesis of a substantial subset of thyroid tumours has yet to be identified; (b) the limitations of the present experimental models, which suggest greater caution in the interpretation of in vitro results; (c) the still unresolved question of absence of genotype-phenotype correlation. Clarification of these issues may hopefully provide new and useful tools for improving the clinical management of this disease.

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    • "HHIP function on T-ALL has not been explored, but an AML study has described the ability of AML-derived stromal cells to express HHIP and to interact with AML stem cells that now re-express SHH and its receptor, smoothened (SMO) (53). TSHR (thyroid stimulating hormone receptor) is not normally considered a T-cell antigen, but mutations of this receptor have been associated with increased vasculature and the development of pituitary adenomas (54, 55). Clinical studies with TSHR primarily focus on Grave‚Äôs disease. "
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