末期肝癌病患合併頑固性低血糖血症：一個案報告

End-stage Hepatocellular Carcinoma with Refractory Hypoglycemia: A Case Report

非胰島細胞腫瘤性低血糖(nonislet cell tumor hypoglycemia, NICTH)是指由胰島細胞瘤以外的其他腫瘤所導致的低血糖症，為一類腫瘤伴生症候群(paraneoplastic syndrome)，雖然臨床上少見卻會危及生命，需要早期診斷與早期治療。肝癌是造成NICTH的常見腫瘤之一，造成低血糖的機轉在於腫瘤組織產生過多的大分子量第二型類胰島素生長因子(macromoleculesinsulin-like growth factor-II, big IGF-II)。Big IGF-II具有類胰島素活性，可刺激胰島素接受器，進而過度增加葡萄糖的利用率、抑制肝臟釋放葡萄糖，也減少了升糖素及生長激素的分泌。其他的原因包括腫瘤產生了對抗胰島素接受器的自體免疫抗體或是因為腫瘤負荷(tumor burden)過大造成其他正常肝臟或腎上腺細胞的破壞等。對於NICTH的治療，根除腫瘤是最有效的方法，如無法達成，應以矯正並預防低血糖為主。最初給予葡萄糖液輸注配合高醣類飲食，若效果不佳，可再使用糖皮質激素、升糖素或人類重組生長激素來治療。本篇藉由分享治療一位末期肝癌病患合併難治性低血糖的經驗，來介紹近年來文獻對於NICTH的流行病學、病理生理機轉、臨床徵狀、診斷及治療之探討。

Nonislet cell tumor hypoglycemia (NICTH) denotes the syndrome of hypoglycemia produced by any neoplasm other than an insulinoma. Hepatocellular carcinomas are one of the most common neoplasms which result in NICTH, a rare but life-threatening paraneoplastic syndrome in need of early diagnosis and treatment. The major cause of NICTH is tumoral overproduction of incompletely processed insulinlike growth factor II, termed "big" IGF-II, which can stimulate insulin receptors and exhibits insulin-like activities. Moreover, big IGF-II also suppresses glucagon and growth hormone release. The net result is continued glucose utilization and inhibition of glucose release, glycogenolysis, and gluconeogenesis in the liver. Other potential but less common causes of NICTH include the production of autoantibodies against insulin or the insulin receptor and extensive tumor burden resulting in destruction of the liver or adrenal glands. The mainstay of treatment for NICTH is surgical resection, which is curative for hypoglycemia if resection is complete. When the underlying malignancy cannot be treated, medical therapy is required to prevent recurrent hypoglycemia symptoms. Other than oral glucose and/or IV glucose- or dextrose-containing fluids, glucocorticoids, glucagon, or recombinant human growth hormone (rhGH) can be added to control intractable hypoglycemia. The case report presents a 28-yearold man of hepatocellular carcinoma with refractory hypoglycemia. Epidemiology, pathophysiology, clinical manifestation, diagnosis, and treatment of NICTH are also introduced after literature review.