1 Department of Internal Medicine 2, Hamamatsu University School of Medicine , Hamamatsu, Japan .
Thyroid. 2014 Feb;24(2):395-9. doi: 10.1089/thy.2013.0141. Epub 2013 Sep 11.
Non-islet cell tumor-induced hypoglycemia (NICTH), a major cause of fasting hypoglycemia, is caused by the overproduction of incompletely processed, high molecular-weight insulin-like growth factor-II (IGF-II), termed "big" IGF-II. To the best of our knowledge, only two cases of thyroid carcinoma associated with NICTH have been documented.
We report the case of a 72-year-old woman who was brought to the emergency department with impaired consciousness. The patient had a history of pulmonary metastases from poorly differentiated thyroid carcinoma (PDTC), spanning 12 years since initial treatment. Laboratory tests showed decreased plasma glucose levels even though immunoreactive insulin, IGF-I, and growth hormone (GH) were undetectable. Computed tomography (CT) scan revealed macronodular pulmonary metastases the estimated volume of which was 456 mL. Both the biochemical data and imaging results suggested NICTH. The results of Western blot analysis performed on a fractionated serum sample showed an increased expression of big IGF-II, an important indicator in the diagnosis of NICTH. Because the massive pulmonary metastases were considered inoperable, immunohistochemical analysis of stored formalin-fixed, paraffin-embedded tissues was performed. The analysis revealed that the tumor cells were positive for both IGF-II and thyroglobulin. A whole-body CT excluded extrapulmonary metastatic lesions. A retrospective review revealed a gradual decrease in glycohemoglobin levels accompanied by an increase in the estimated volume of pulmonary metastases. These findings suggested that NICTH had been caused by pulmonary metastases from PDTC.
We describe here the third reported case of NICTH associated with thyroid carcinoma. This is also the first case reporting big IGF-II in the serum of a patient with thyroid carcinoma.
非胰岛细胞瘤肿瘤导致的低血糖（NICTH）是空腹低血糖的主要原因，是由不完全加工的高分子量胰岛素样生长因子-II（IGF-II），即“大”IGF-II 的过度产生引起的。据我们所知，仅有两例甲状腺癌相关的 NICTH 病例被记录在案。
我们报告了一例 72 岁女性因意识障碍被带到急诊室的病例。该患者患有分化差的甲状腺癌（PDTC）的肺转移，自最初治疗以来已有 12 年。实验室检查显示尽管免疫反应性胰岛素、IGF-I 和生长激素（GH）无法检测到，但血浆葡萄糖水平降低。计算机断层扫描（CT）显示大结节性肺转移，估计体积为 456 毫升。生化数据和影像学结果均提示 NICTH。对部分血清样本进行的 Western blot 分析结果显示，大 IGF-II 的表达增加，这是 NICTH 诊断的重要指标。由于巨大的肺转移灶被认为无法手术，对储存的福尔马林固定、石蜡包埋组织进行了免疫组织化学分析。分析显示肿瘤细胞对 IGF-II 和甲状腺球蛋白均呈阳性。全身 CT 排除了肺外转移病灶。回顾性分析显示糖化血红蛋白水平逐渐下降，同时肺转移灶的估计体积增加。这些发现表明 NICTH 是由 PDTC 引起的肺转移引起的。
我们在此描述了第三例与甲状腺癌相关的 NICTH 病例。这也是首例报告甲状腺癌患者血清中大 IGF-II 的病例。
