Wermers R A, Fatourechi V, Kvols L K
Division of Endocrinology/Metabolism and Internal Medicine, Mayo Clinic Rochester, Minnesota 55905, USA.
Mayo Clin Proc. 1996 Nov;71(11):1030-8. doi: 10.4065/71.11.1030.
To review the clinical features associated with hyperglucagonemia in malignant neuroendocrine tumors.
We retrospectively reviewed the medical records of patients with hyperglucagonemia encountered at our institution from Oct. 17, 1988, through February 1993 who had a fasting serum glucagon level of at least 120 pg/mL (twice the normal value). The 71 study patients also had no evidence of a secondary cause of hyperglucagonemia and had pathologic confirmation of a neuroendocrine tumor.
The study group consisted of 46 men and 25 women with a median age of 57 years. Two patients had multiple endocrine neoplasia. Forty-nine patients had biochemically polyfunctional tumors, and 22 had hyperglucagonemia only. The most common initial symptoms were weight loss, abdominal pain, diarrhea, nausea, peptic ulcer disease, diabetes, and necrolytic migratory erythema (NME). Diabetes eventually developed in 25 patients and was associated with NME in 11. The highest median serum glucagon values occurred in patients with the glucagonoma syndrome or insulinomas, and the lowest median values were in those with carcinoid syndrome, Zollinger-Ellison syndrome, or diabetes without NME. Fasting glucagon and glucose measurements were not correlated. The most common hormonal syndromes were the Zollinger-Ellison syndrome and the glucagonoma syndrome. All the neuroendocrine tumors were malignant. Several methods of treatment, including surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization, were used. Death occurred in 29 patients at a median of 2.79 years after diagnosis; 42 patients were alive at a median of 2.86 years after diagnosis.
A mild degree of hyperglucagonemia can commonly be associated with multifunctional neuroendocrine tumors. The glucagonoma syndrome occurs in a few patients with malignant neuroendocrine tumors and hyperglucagonemia and is associated with very high serum glucagon levels. The correlation between serum glucagon levels and the development of diabetes is limited, and other factors such as insulin may be more important than hyperglucagonemia in the development of diabetes.
回顾恶性神经内分泌肿瘤中与高胰高血糖素血症相关的临床特征。
我们回顾性分析了1988年10月17日至1993年2月期间在我院遇到的高胰高血糖素血症患者的病历，这些患者空腹血清胰高血糖素水平至少为120 pg/mL（正常值的两倍）。71例研究患者也没有高胰高血糖素血症的继发原因证据，且有神经内分泌肿瘤的病理证实。
研究组包括46名男性和25名女性，中位年龄为57岁。2例患者有多发性内分泌肿瘤。49例患者有生化多功能肿瘤，22例仅有高胰高血糖素血症。最常见的初始症状是体重减轻、腹痛、腹泻、恶心、消化性溃疡病、糖尿病和坏死性游走性红斑（NME）。最终25例患者出现糖尿病，其中11例与NME相关。血清胰高血糖素中位数最高值出现在胰高血糖素瘤综合征或胰岛素瘤患者中，中位数最低值出现在类癌综合征、卓-艾综合征或无NME的糖尿病患者中。空腹胰高血糖素和血糖测量值无相关性。最常见的激素综合征是卓-艾综合征和胰高血糖素瘤综合征。所有神经内分泌肿瘤均为恶性。采用了几种治疗方法，包括手术减瘤、化疗、生长抑素和肝动脉栓塞。29例患者在诊断后中位2.79年死亡；42例患者在诊断后中位2.86年存活。
轻度高胰高血糖素血症通常与多功能神经内分泌肿瘤相关。胰高血糖素瘤综合征发生在少数恶性神经内分泌肿瘤和高胰高血糖素血症患者中，且与非常高的血清胰高血糖素水平相关。血清胰高血糖素水平与糖尿病发生之间的相关性有限，在糖尿病发生中胰岛素等其他因素可能比高胰高血糖素血症更重要。
