Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
J Clin Endocrinol Metab. 2011 Dec;96(12):E2039-44. doi: 10.1210/jc.2011-1114. Epub 2011 Oct 5.
Heterozygous inactivating PAX8 mutations cause congenital hypothyroidism. Although more than 30 mutation carriers have been reported, no histological examination of the thyroid has been conducted.
The objective of this study was to document the histological characteristics of the thyroid tissue harboring a PAX8 mutation.
The patient was a 40-yr-old female, whose two children had congenital hypothyroidism and an inactivating PAX8 mutation (p.K80_A84dup). She had normal thyroid function but had a thyroid nodule and received right hemithyroidectomy at age 28 yr. Mutation analyses using DNA derived from multiple sources, namely lymphocytes, nails, and laser capture microdissected thyroid samples, were performed.
The PAX8 mutation was detected in the lymphocytes; however, the level of the mutant allele was significantly lower than that of the wild-type allele. This finding was compatible with her somatic mosaic state. We reviewed the histology of her resected thyroid and found a characteristic lesion in the nonneoplastic tissue: dense aggregates of thyrocytes with absent or very small follicles, resembling a fetal thyroid in the late phase of development. Mutation analyses of laser capture microdissected thyroid samples revealed that the fetal-like tissue carried the PAX8 mutation, whereas surrounding morphologically normal tissue and adenoma tissue did not.
In our case, the histology of PAX8 mutation-carrying thyroid tissue was characterized by the lack of follicular growth. Our observations provide the first evidence suggesting that the late phase of thyroid development is sensitive to the PAX8 gene dosage and can be disturbed by heterozygous inactivating PAX8 mutations.
PAX8 杂合失活突变可导致先天性甲状腺功能减退症。尽管已经报道了 30 多个突变携带者，但尚未对甲状腺进行组织学检查。
本研究旨在记录携带 PAX8 突变的甲状腺组织的组织学特征。
患者为 40 岁女性，其两名子女均患有先天性甲状腺功能减退症和 PAX8 失活突变（p.K80_A84dup）。她甲状腺功能正常，但有甲状腺结节，并于 28 岁时接受了右半甲状腺切除术。使用来自多个来源（即淋巴细胞、指甲和激光捕获显微解剖甲状腺样本）的 DNA 进行突变分析。
在淋巴细胞中检测到 PAX8 突变；然而，突变等位基因的水平明显低于野生型等位基因。这一发现与她的体细胞镶嵌状态相符。我们回顾了她切除的甲状腺组织学，发现了一种非肿瘤组织的特征性病变：大量密集的甲状腺细胞聚集，没有或只有非常小的滤泡，类似于发育晚期的胎儿甲状腺。对激光捕获显微解剖甲状腺样本的突变分析表明，胎儿样组织携带 PAX8 突变，而周围形态正常的组织和腺瘤组织则没有。
在我们的病例中，携带 PAX8 突变的甲状腺组织的组织学特征是滤泡生长缺乏。我们的观察结果首次提供了证据，表明甲状腺发育的晚期阶段对 PAX8 基因剂量敏感，并且可能受到杂合失活 PAX8 突变的干扰。
