alexa Hot microscopic areas of iodine-deficient euthyroid goitres contain constitutively activating TSH receptor mutations.
Oncology

Oncology

Journal of Nuclear Medicine & Radiation Therapy

Author(s): Krohn K, Wohlgemuth S, Gerber H, Paschke R

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Abstract Constitutively activating TSH receptor mutations have been established as the most common molecular basis for the pathogenesis of toxic thyroid nodules. These mutations result in uncontrolled signalling through the TSH receptor that is likely to cause hyperfunction and proliferation. The incidence of toxic multinodular goitres has been demonstrated to be related to iodine deficiency. Moreover, scintigraphically autonomous areas are found in 40\% of euthyroid goitres from iodine-deficient areas. To investigate the molecular cause of these autonomous areas, small autoradiographically hot areas were examined for somatic TSH receptor mutations using archival tissue sections from 14 patients with euthyroid goitres, which had been originally prepared nearly 20 years ago. All patients had received (125)I 17 h preoperatively for the autoradiographic investigation of their thyroid. Areas with high and low (125)I-labelling on autoradiography sections were collected separately either from serial paraffin-embedded tissue sections, or Eukitt-embedded tissue sections containing the autoradiograph. After genomic DNA extraction, the transmembrane segment of the TSH receptor was PCR-amplified and directly sequenced. Somatic TSH receptor mutations were identified in areas with high (125)I-labelling in four patients: A623I, L629P, F631L, and T632I. This is the first evidence that TSH receptor mutations occur in microscopic areas with increased (125)I-labelling in euthyroid goiters and it suggests that TSH receptor mutations in these areas confer the potential to develop into toxic thyroid nodules. It is therefore very likely that toxic thyroid nodules originate from small autonomous areas in iodine-deficient euthyroid goitres that contain a TSH receptor mutation. Copyright 2000 John Wiley & Sons, Ltd. This article was published in J Pathol and referenced in Journal of Nuclear Medicine & Radiation Therapy

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