Medeiros-Neto G A, Knobel M, Cavaliere H, Simonetti J, Mattar E
Clin Endocrinol (Oxf). 1984 Jun;20(6):631-42. doi: 10.1111/j.1365-2265.1984.tb00113.x.
The thyroid glands of two hypothyroid goitrous siblings aged 13 and 14 and of a 21-year-old hypothyroid goitrous female were examined. In all three patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12.9-20.0 micrograms/dl) and low serum T4 concentration suggested the presence of increased serum levels of iodoalbumin. Surprisingly, serum T3 levels were normal or low normal (80-220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. Serum thyroglobulin was undetectable in one patient, low normal in another and in the normal range for the third one. Except for the patient with undetectable Tg the two other subjects slightly increased the serum Tg levels after a bovine TSH injection. Plasma chromatography after a tracer dose of 125I disclosed only minute amounts of T3 + T4 and MIT + DIT. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg-like proteins (RIA) in the thyroid soluble protein extract was only 16-122 micrograms/g (normal: 50-70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18-20S) thyroglobulin. Only one peak (3.6-4.1S) was obtained in the pooled soluble proteins supernatants. Hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively large amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. We conclude that a defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA finally results in deficient storage of normal, mature Tg in the colloid with subsequent goitrous hypothyroidism.
对一名13岁和一名14岁的甲状腺功能减退性甲状腺肿同胞以及一名21岁的甲状腺功能减退性甲状腺肿女性的甲状腺进行了检查。在所有三名患者中，尽管高氯酸盐释放试验呈阴性，但仍观察到甲状腺对碘的摄取非常高。血清蛋白结合碘异常升高（12.9 - 20.0微克/分升）且血清T4浓度降低，提示血清碘白蛋白水平升高。令人惊讶的是，多次测定中血清T3水平正常或略低于正常（80 - 220纳克/分升）。基础血清促甲状腺激素（TSH）升高，注射促甲状腺激素释放激素（TRH）后观察到TSH反应增强。一名患者血清甲状腺球蛋白检测不到，另一名患者略低于正常，第三名患者在正常范围内。除了甲状腺球蛋白检测不到的患者外，另外两名受试者注射牛TSH后血清甲状腺球蛋白水平略有升高。给予示踪剂量的125I后进行血浆色谱分析，仅发现微量的T3 + T4和MIT + DIT。对甲状腺组织匀浆进行的研究表明，这些甲状腺肿腺体中免疫反应性甲状腺球蛋白明显减少。甲状腺可溶性蛋白提取物中类甲状腺球蛋白（RIA）的总量仅为16 - 122微克/克（正常：50 - 70毫克/克组织）。超速离心研究未能证明存在成熟的（18 - 20S）甲状腺球蛋白。在合并的可溶性蛋白上清液中仅获得一个峰（3.6 - 4.1S）。通过随后的柱色谱分析表明，匀浆水解后，碘酪氨酸和碘甲状腺原氨酸的相对浓度非常低，并且相对大量的碘仍与亚细胞蛋白结合且未被消化。主要的组织学模式为中间分化型腺瘤，微滤泡型或胎儿型，具有一些非典型特征和包膜侵犯，这可能提示恶性改变。我们得出结论，从细胞向腺腔的甲状腺球蛋白输出缺陷或结构基因异常导致甲状腺球蛋白mRNA翻译不足，最终导致胶体中正常成熟甲状腺球蛋白储存不足，继而发生甲状腺肿性甲状腺功能减退。
