Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy.
Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy.
复制标题
单羧酸转运蛋白 8 缺乏：甲状腺形态改变，甲状腺切除术后三碘甲状腺原氨酸/甲状腺素比率持续升高。
DOI：
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发表时间：
2011
影响因子：
5.8
通讯作者：
A. Grüters
中科院分区：
文献类型：
--
作者：
E. Wirth;S. Sheu;J. Chiu;R. Sapin;M. Klein;I. Mossbrugger;L. Quintanilla‐Martinez;M. D. de Angelis;H. Krude;T. Riebel;K. Rothe;J. Köhrle;K. Schmid;U. Schweizer;A. Grüters
背景
甲状腺激素跨质膜的转运依赖于跨膜转运蛋白，包括单羧酸转运蛋白 8 (MCT8)。 MCT8（或SLC16A2）突变导致严重形式的X连锁精神运动迟缓，其特征是血浆三碘甲状腺原氨酸（T（3））升高和甲状腺素（T（4））低/正常。 MCT8 有助于甲状腺释放激素。
目标
旨在描述 MCT8 缺陷对患者和 Mct8 缺陷小鼠甲状腺形态的潜在影响。
设计
对携带 A224V 突变的患者的甲状腺形态进行了 10 多年的超声成像跟踪。甲状腺切除术后，进行组织病理学分析。研究结果与 Mct8(-/y) 模型小鼠甲状腺的组织学分析进行了比较。
结果
我们发现 MCT8 的失活突变会导致患者出现独特的进行性甲状腺滤泡病理学。甲状腺切除术后，组织学分析显示了总体形态学变化，包括几个增生结节、间质纤维化的微滤泡区域以及具有核特征让人想起甲状腺乳头状癌（PTC）的微滤泡结构的小病灶。这些发现得到了 Mct8 缺失小鼠模型的支持，在该模型中，我们发现 6 至 12 个月大的小鼠存在大量乳头状增生，并且在近 2 岁的动物中发现了与 PTC 一致的核特征。甲状腺完全切除并用左旋甲状腺素（l-T(4)）替代后，术前T(4)和游离T(4)过低的状态仍然存在，而增加l-T(4)剂量导致T(3)血清浓度高于正常范围。
结论
我们的结果表明 MCT8 缺陷患者的特殊激素群中存在外周脱碘。应密切监测其他 MCT8 缺陷患者是否存在潜在的甲状腺异常。
CONTEXT
Thyroid hormone transport across the plasma membrane depends on transmembrane transport proteins, including monocarboxylate transporter 8 (MCT8). Mutations in MCT8 (or SLC16A2) lead to a severe form of X-linked psychomotor retardation, which is characterised by elevated plasma triiodothyronine (T(3)) and low/normal thyroxine (T(4)). MCT8 contributes to hormone release from the thyroid gland.
OBJECTIVE
To characterise the potential impact of MCT8-deficiency on thyroid morphology in a patient and in Mct8-deficient mice.
DESIGN
Thyroid morphology in a patient carrying the A224V mutation was followed by ultrasound imaging for over 10 years. After thyroidectomy, a histopathological analysis was carried out. The findings were compared with histological analyses of mouse thyroids from the Mct8(-/y) model.
RESULTS
We show that an inactivating mutation in MCT8 leads to a unique, progressive thyroid follicular pathology in a patient. After thyroidectomy, histological analysis revealed gross morphological changes, including several hyperplastic nodules, microfollicular areas with stromal fibrosis and a small focus of microfollicular structures with nuclear features reminiscent of papillary thyroid carcinoma (PTC). These findings are supported by an Mct8-null mouse model in which we found massive papillary hyperplasia in 6- to 12-month-old mice and nuclear features consistent with PTC in almost 2-year-old animals. After complete thyroidectomy and substitution with levothyroxine (l-T(4)), the preoperative, inadequately low T(4) and free T(4) remained, while increasing the l-T(4) dosage led to T(3) serum concentrations above the normal range.
CONCLUSIONS
Our results implicate peripheral deiodination in the peculiar hormonal constellation of MCT8-deficient patients. Other MCT8-deficient patients should be closely monitored for potential thyroid abnormalities.
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影响因子：
11.2
作者：
D. Powell;John C. Russell;K. Nibu;Guoqi Li;E. Rhee;M. Liao;Michael R. Goldstein;W. Keane;M. Santoro;A. Fusco;J. Rothstein
通讯作者：
D. Powell;John C. Russell;K. Nibu;Guoqi Li;E. Rhee;M. Liao;Michael R. Goldstein;W. Keane;M. Santoro;A. Fusco;J. Rothstein
影响因子：
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作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
Refetoff, Samuel
影响因子：
4.8
作者：
Dumitrescu, Alexandra M.;Liao, Xiao-Hui;Refetoff, Samuel
通讯作者：
Refetoff, Samuel