Tonacchera M, Vitti P, Agretti P, Giulianetti B, Mazzi B, Cavaliere R, Ceccarini G, Fiore E, Viacava P, Naccarato A, Pinchera A, Chiovato L
Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa, Cisanello, Italy.
Thyroid. 1998 Jul;8(7):559-64. doi: 10.1089/thy.1998.8.559.
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 Gs alpha 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.
在毒性腺瘤和毒性多结节性甲状腺肿中的热结节中发现了激活促甲状腺激素（TSH）受体突变。多结节性甲状腺肿的典型特征是同一肿大腺体中不同滤泡在形态和功能上的异质性。在本报告中，我们描述了一名患有巨大多结节性甲状腺肿的患者，其血清游离三碘甲状腺原氨酸（FT3）和游离甲状腺素（FT4）值正常，血清促甲状腺激素（TSH）浓度低于正常水平。甲状腺闪烁扫描显示两个热区，分别对应左叶的底部和顶部结节。放射性同位素对右叶的显影不佳。患者接受了甲状腺切除术，并对组织进行了组织学检查。从组织标本中提取基因组DNA，并对TSH受体和Gsα基因进行直接测序。组织学检查发现，一个功能亢进的结节具有甲状腺腺瘤的典型微观结构，另一个则包含多个不受包膜限制的大滤泡区域。尽管存在这种组织学差异，但两个功能亢进的结节均存在促甲状腺激素受体（TSHr）基因突变：第一个结节中第632位的异亮氨酸替代了苏氨酸（T632I），第二个结节中第486位的甲硫氨酸替代了异亮氨酸（I486M）。总之，我们的研究结果首次表明，功能获得性TSHr突变不仅存在于具有真正甲状腺腺瘤组织学特征的功能亢进性甲状腺结节中，也存在于同一多结节性甲状腺肿中功能亢进的增生性结节中。
