Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular goiter

Massimo Tonacchera, Paolo Vitti, Patrizia Agretti, Barbara Giulianetti, Barbara Mazzi, Rossana Cavaliere, Giovanni Ceccarini, Emilio Fiore, Paolo Viacava, Antonio Naccarato, Aldo Pinchera, Luca Chiovato

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Activating thyrotropin (TSH) receptor mutations have been found in toxic adenomas and in hot nodules contained in toxic multinodular goiter. The typical feature of multinodular goiter is the heterogeneity in morphology and function of different follicles within the same enlarged gland. In this report we describe a patient with a huge multinodular goiter, normal free triiodothyronine (FT3) and free thyroxine (FT4) serum values, and subnormal TSH serum concentration. Thyroid scintiscan showed two hot areas corresponding to the basal and apical nodules of the left lobe. The right lobe was poorly visualized by the radioisotope. The patient underwent thyroidectomy, and histological examination of the tissue was performed. Genomic DNA was extracted from the tissue specimen and direct sequencing of the TSH receptor and Gsα genes was done. At histology, one hyperfunctioning nodule had the typical microscopic structure of thyroid adenomas, and the other contained multiple macrofollicular areas not confined by a capsule. In spite of this histological difference, both hyperfunctioning nodules harbored a mutation of the thyrotropin receptor (TSHr) gene: an isoleucine instead of a threonine in position 632 (T632I) in the first nodule and a methionine instead of an isoleucine in position 486 (I486M) in the second nodule. In conclusion, our findings show for the first time that gain-of-function TSHr mutations are not only present in hyperfunctioning thyroid nodules with the histological features of the true thyroid adenomas, but also in hyperfunctioning hyperplastic nodules contained in the same multinodular goiter.

Original languageEnglish
Pages (from-to)559-564
Number of pages6
Issue number7
Publication statusPublished - 1998


ASJC Scopus subject areas

  • Endocrinology

Cite this

Tonacchera, M., Vitti, P., Agretti, P., Giulianetti, B., Mazzi, B., Cavaliere, R., Ceccarini, G., Fiore, E., Viacava, P., Naccarato, A., Pinchera, A., & Chiovato, L. (1998). Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular goiter. Thyroid, 8(7), 559-564.