胰岛素瘤10例临床特点分析

目的 分析胰岛素瘤的临床表现特点，为诊断和治疗提供帮助。方法 回顾性分析2000年10月至2006年4月北京大学第一医院住院手术且术后病理诊断的胰岛素瘤10例临床资料。结果 （1）10例患者均表现有晨起或饥饿时发作性出冷汗、心慌等交感神经兴奋及头晕、乏力症状，其中9例进食或喝糖水后可缓解。9例有晕厥、昏迷等意识障碍，6例有惊厥、抽搐或癫痫发作，5例进食多且体重增加超过10kg。（2）8例血糖〈2．8mmol／L，7例胰岛素血糖比值〉0．4，9例胰岛素修正释放指数〉100。（3）B超、CT和术中探查阳性率分别为30％、60％和100％。结论 典型低血糖症状、Whipple三联症和胰岛素血糖比值、胰岛素修正释放指数是胰岛素瘤定性诊断主要依据，术中B超结合术中探查和脾门静脉分段取血是最有效的肿瘤定位手段。临床表现典型而影像学检查阴性病例应考虑剖腹探查术。     

胰岛素瘤的诊断和治疗

目的 总结胰岛素瘤的诊断和治疗经验,以期提高手术成功率和改善预后.方法 回顾性分析1966年至2007年收治的138例胰岛素瘤患者的临床资料.结果 全组病例均有不同程度的低血糖症状和Whipple三联征表现;64例有不同程度的精神神经症状,12例术后血糖恢复正常,但仍遗留精神神经症状.检测空腹血胰岛素88例,胰岛素释放指数均>0.3.术前B超检查75例,检出肿瘤8例;腹部CT 68例,检出17例;腹部MRI检查10例,检出5例;术中B超44例,检出肿瘤43例,另1例病理证实为胰岛细胞增生症.135例行手术治疗,其中肿瘤摘除术88例,胰体尾切除44例,胰十二指肠切除2例,活检1例.132例术后血糖恢复正常.术后血糖反跳性升高110例,多于术后2周内恢复正常;术后胰瘘20例,急性胰腺炎32例.结论 根据whipple三联征和胰岛素释放指数对胰岛素瘤作出定性诊断.手术探查联合术中B超是简单有效的定位诊断方法.手术是治愈胰岛素瘤的惟一方法.术中B超引导下切除肿瘤可有效避免主胰管和血管的损伤,降低手术并发症.     

胰岛素瘤的定位诊断方法

对41例胰岛素瘤患者的临床资料作回顾性分析,发现术前B超、CT、MRI、选择性动脉造影（AS）检查定位诊断的阳性率分别为45%（18/40）、62.5%（20/32）、66.7%（10/15）、80%（8/10）,术中B超检查为100% （15/15）。认为胰岛素瘤的术前定位诊断较为困难,手术探查加术中B超检查是定位诊断的最佳方法。     

胰岛素瘤的术前定性及定位诊断99例分析

目的分析不同的激素检查和影像学检查方法对胰岛素瘤术前诊断的价值。方法回顾性总结分析北京协和医院1989年12月至2005年8月入院的有明确术后病理诊断的胰岛素瘤患者的临床资料。结果本组患者的临床表现以昏迷、体重增加、大汗、定向力障碍、记忆力减退、头晕头痛为主。空腹血糖低于2.78mmol/L对于诊断胰岛素瘤的敏感性为66.6%;发作时的血清胰岛素血糖比值大于0.3的敏感性为89.7%;常用的影像学检查中胰腺灌注CT的敏感性最高,可达100.0%。结论典型的Whipple三联症和低血糖时的血清胰岛素血糖比值大于0.3是胰岛素瘤定性诊断的重要依据。目前常用的影像学检查手段中,胰腺灌注CT对于胰岛素瘤诊断的敏感性和特异性最高。     

胰岛素瘤的定位诊断及外科治疗方法探讨

目的 探讨胰岛素瘤的定位诊断及外科治疗方法。方法 对确诊的18例胰岛素瘤患者的临床资料进行回顾性分析。结果 术前B超、CT和选择性动脉造影检查的阳性率分别为46％(7／15)、54%(7/13)和75％(6／8)，术中B超检查的阳性率为100％(5／5)。18例中行肿瘤剜除术11例，胰体尾切除术7例。结论 胰岛素瘤的术前定位诊断比较困难，术中探查和术中B超检查准确性很高；手术切除是胰岛素瘤惟一可靠的治疗方法。     

胰岛素瘤的术前及术中定位诊断方法的探讨

目的 探讨胰岛素瘤术前、术中定位方法的诊断价值,以提高胰岛素瘤定位的准确性.方法 对75例经手术病理证实的胰岛素瘤患者术前B超、CT、MRI的定位资料进行分析,统计术中触诊、术中超声(IOUS)等方法对胰岛素瘤的定位诊断准确率,并进行总结分析.结果 术前B超检查75例,23例发现肿瘤,诊断正确率30.7%;CT检查60例,24例发现肿瘤,诊断正确率40.0%;行MRI 48例,22例发现肿瘤,诊断正确率为45.8%.而术中扪诊、IOUS定位准确率分别为80.4%和96.4%术中定位率比术前明显提高.结论 胰岛索瘤的术前定位诊断比较困难,术中探查和术中B超检查的准确性很高,可不必强调术前准确定位和多种影像学重复检查.     

31例胰岛素瘤临床及定位诊断分析

目的提高对胰岛素瘤的认识、诊断和治疗。方法对31例胰岛素瘤患者的临床资料和定位诊断进行总结分析。结果患者病程3周~14年,23例手术治疗,术后病理诊断为胰岛细胞瘤,其中2例多发内分泌腺瘤(MEN-1型)。8例未行手术治疗,经临床检查诊断为胰岛素瘤。31例中有28例有典型的Whipple三联症,住院期间低血糖发作,血糖在0.57~2.7mmol/L之间。23例INS(血浆胰岛素)/G(血糖)>0.3。影像学检查阳性率:超声检查为53.3%,CT为50%,血管造影(DSA)为78.9%,内镜超声(EUS)为91.6%。结论胰岛素瘤患者常反复发作低血糖、有各种交感神经兴奋及神经精神症状,影像学检查以EUS、DSA检出率为高。尤其EUS检查创伤小,阳性率高,应作为临床胰岛素瘤定位诊断的主要手段之一。     

胰岛素瘤的数字减影血管造影诊断

胰岛素瘤是胰岛的Ｂ细胞肿瘤 ,瘤体直径仅 10～ 2 0ｍｍ ,定位诊断比较困难。本文分析经手术病理证实的 2 2例胰岛素瘤的数字减影血管造影 (ＤＳＡ)等影像学资料 ,以探讨其在胰岛素瘤诊断中的价值。一、资料和方法2 2例中男 9例 ,女 13例。年龄 19～ 81岁 ,平均 49岁。病程 2个月～ 8年。所有患者均有典型的Ｗｈｉｐｐｌｅ三联征 ,其中 10例在低血糖发作时伴有抽搐、精神错乱、言语不清和运动失调等神经精神症状。实验室检查 2 2例空腹和发作时血糖均明显低于正常 ,血清胰岛素水平升高。2 2例术前均作Ｂ超和ＤＳＡ检查。ＤＳＡ采用Ｓｅｌｄ…     

胰岛素瘤的术前定性及定位诊断99例分析

目的 分析不同的激素检查和影像学检查方法对胰岛素瘤术前诊断的价值。方法 回顾性总结分析北京协和医院1989年12月至2005年8月入院的有明确术后病理诊断的胰岛素瘤患者的临床资料。结果 本组患者的临床表现以昏迷、体重增加、大汗、定向力障碍、记忆力减退、头晕头痛为主。空腹血糖低于2．78mmol／L对于诊断胰岛素瘤的敏感性为66．6％；发作时的血清胰岛素血糖比值大于0．3的敏感性为89．7％；常用的影像学检查中胰腺灌注CT的敏感性最高，可达100.0％。结论 典型的Whipple三联症和低血糖时的血清胰岛素血糖比值大于0．3是胰岛素瘤定性诊断的重要依据。目前常用的影像学检查手段中，胰腺灌注CT对于胰岛素瘤诊断的敏感性和特异性最高。     

胰岛素瘤62例诊治体会

目的：总结胰岛素瘤的诊治经验，评估胰岛素瘤的多种定位诊断技术。方法：回顾性分析两院1970年-2001年来收治的62例胰岛素瘤的临床资料。结果：CT、MRI、术前B超、SAOG及IOUS诊断胰岛素瘤的敏感性分别为46.4%、70.0%、75.6%、75.9和100%；手术治疗60例，其中实施肿瘤剜除术41例，胰体尾切除术14例，胰十二指肠切除术3例，楔形切除术1例，姑息手术1例，总手术切除率98.3%；全组无手术死亡，肿瘤切除术后病人随访无低血糖发作；术后并发症包括胰瘘5例、胰腺假性囊肿2例。结论：术前B超和SAOG、术中详尽扪诊联合IOUS可基本上取得胰岛素瘤较为满意的定位诊断；根据胰岛素瘤的大小、部位、数目及性质采取适宜的手术方式是获得良好疗效的关键。     

胰岛素瘤误诊原因探讨和处理对策（附71例报告）

目的：分析胰岛素瘤误诊原因，探讨避免误诊、误治的策略。方法：对1990年1月至2001年9月北京协和医院收治的71例胰岛素瘤患的临床资料进行回顾性分析。结果：本组患从发病到确诊时间为3个月－30年，平均4．24年，1年内获得确诊17例，占23．9％。93％的患有被误诊的病中，最常见的误诊原因分别为反应性低血糖（38％）、癫痫（23．9％）、颅内病变（21．1％）和脑血管病（12．6％）；4．2％的患被误诊为精神病。在获得确诊时，54．9％的患有不同程度的记忆力下降，智力减退或反应迟钝。结论：Whipple三联征和胰岛素／血糖（I／G）＞0．3是胰岛素瘤定性诊断的主要依据。提高对胰岛素瘤的警惕性，合理应用辅助检查，有助于减少误诊。对定性诊断明确的患，无论能否获得定位诊断，均应及早手术探查，以免延误治疗。     

Insulinoma with hyperproinsulinemia: a two cases report

We report two cases of insulinoma with increased serum proinsulin levels and with normal insulin levels.Clinically, the two patients show typical symptoms of insulinoma, but serum insulin levels are normal.Only high levels of serum proinsulin allow us to retain the diagnosis of insulinoma. The new insulin assays using monoclonal antibodies are very specific for insulin and though can not detect isolated high proinsulin levels. So proinsulin assay is useful when diagnosing insulinoma.     

Endogenous hyperinsulinemic hypoglycemia: diagnostic strategies, predictive features of malignancy and long-term survival

Diagnostic strategies, malignancy predictors and long-term survival were retrospectively evaluated in patients with hyperinsulinemic hypoglycemia (64 insulinomas). Lower median glycemia was 30 (range 20-53) mg/dl [1.6 (1.1-2.9) mmol/l] with concurrent insulin of 48 (13.2-217) microU/ml and 15 (2-46) microU/ml measured by radioimmunoassay (RIA) and immunofluorimetric assay (IFMA), respectively. All patients with insulinomas had a positive prolonged fast within 48 h. Sensitivity of localization methods was: ultrasonography (US) 23%, computed tomography (CT) 28%, magnetic resonance imaging (MRI) 65%, endoscopic US 75%, arteriography 38%, portal venous sampling 67%, selective arterial calcium stimulation 67%, intraoperative US 94% and palpation 92%. Nine patients (14%) had malignant insulinomas. Age at diagnosis (mean+/-SD, 53.8+/-19 vs 39.4+/-16.3 yr; p=0.03), insulin (1372+/-730 vs 785+/-659% (percentage of the method's diagnostic cut-off; 6 and 3 microU/ml for RIA and IFMA, respectively; p=0.007) and C-peptide levels (9.8+/-2.9 vs 3.9+/-2.8 ng/ml (3.2+/-0.9 vs 1.3+/-0.9 nmol/l; p=0.006), and tumor size (6.2+/-4.1 vs 1.5+/-0.6 cm; p=0.0002) were increased in malignant insulinomas. C-peptide level above 6.1 ng/ml (2.0 nmol/l) had a 100% sensitivity and 96% specificity, and tumor size above 2.6 cm yielded a sensitivity of 88% and specificity of 100% in predicting malignancy. Survival of patients with malignant insulinomas was significantly impaired (16 vs 100% at 5 yr; p=0.0000001). The diagnosis of insulinoma can be made within 48 h of fasting. The association between intraoperative US and palpation evidenced the tumor in 95% of the patients. C-peptide and tumor size were reliable malignancy predictors.     

Diagnosis of non-Zollinger-Ellison syndrome, non-carcinoid syndrome, enteropancreatic neuroendocrine tumours

The diagnosis of entero-neuropancreatic tumours different from Zollinger-Ellison syndrome and carcinoid syndrome require an high index of suspicion and even when they are associated to virulent syndromes such as VIPoma or insulinoma syndrome the mean delay in diagnosis is of 4 years. Symptomatic hypoglycaemia due to inappropriate insulin release from insulinoma and watery diarrhoea leading to dehydration caused by elevated circulant vaso-intestinal peptide levels are present in the 90% and 100% of the patients at presentation of the respective syndrome. Somatostatinoma syndrome has a far more subtle presentation and it tends to present much later during the disease course. The diagnosis is based on the presence of gallstones, diabetes, weight loss, diarrhoea and steatorrhoea. Growth hormone releasing factor neuroendocrine tumours (GRFoma) present with acromegaly and account for less than 2% of the acromegalic patients in which the growth hormone is from an ectopic source located in the pancreas. The Cushing's syndrome diagnosis due to rare ectopic neuroendocrine tumour adrenocorticotropic hormone secretion can be made only with selective angiography, whereas non-functional and pancreatic polypeptide producing neuroendocrine tumours (PPoma) present without any symptoms. Finally, multiple endocrine neoplasia type one occurs more commonly with somatostatinoma or GRFoma, conversely patients with multiple endocrine neoplasia type one can develop insulinoma (20%) or PPoma (60%).     

Insulinoma of the pancreas--difficulties with imaging

We present a case of 29-year old man in whom despite the lack of finding tumor in USG and CT surgical intervention was performed and insulinoma of the pancreas was excised. Insulinoma was diagnosed on the basis of clinical picture (Whipple's triade) that was reassured by positive fast test. The fast was terminated at 11 and half hours because of neuroglycopenic symptoms with serum glucose and insulin levels 2.0 mmol/l (36 mg/dl) and 11.07 microU/ml respectively, which established the diagnosis. Laparotomy was performed, during which the tumor was palpated and seen in ultrasonography in the head of pancreas. The tumor of 12 mm diameter was excised. Histopathological examination revealed benign insulinoma. After surgery the symptoms alleviated completely. The patient with proper glucose levels was discharged in good health. The case supports high usefulness of intraoperative ultrasonography and surgeon's palpation.     

Forty-eight-hour fast: the diagnostic test for insulinoma

Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. Its diagnosis is based on demonstrating Whipple's triad during a supervised 72-h fast. For 75 yr, the 72-h fast has been the cornerstone for the diagnosis; however, it has never been critically assessed using newer assays for insulin, C peptide, and proinsulin. Thus, the aim of the current study is to assess the need for a full 72-h fast for the diagnosis of insulinoma. Patients with suspected hypoglycemia with documented glucose concentrations below 45 mg/dL were admitted to the NIH. Data obtained during the supervised fast of patients with pathologically proven insulinoma over a 30-yr period (1970-2000) were reviewed. We identified 127 patients with insulinoma. The average age of patients was 42.7 +/- 15.9 yr, with a predominance of females (62%). 107 patients had a benign tumor, 20 had malignant insulinoma, and 15 patients had multiple endocrine neoplasia type 1. The fast was terminated due to hypoglycemia in 44 patients (42.5%) by 12 h, 85 patients (66.9%) by 24 h, and 120 (94.5%) by 48 h. Seven patients fasted beyond 48 h despite subtle neuroglycopenic symptoms and glucose and insulin concentrations diagnostic of insulinoma. Immunoreactive proinsulin was elevated at the beginning of the fast in 90% of 42 patients. Proinsulin in noninsulinoma, in contrast to insulinoma, patients is usually suppressible; therefore, samples taken in the suppressed state have the greatest diagnostic value. We conclude that with the current available insulin and proinsulin assays, the diagnosis of insulinoma can be made within 48 h. Thus, the 48-h fast should replace the 72-h fast in textbooks and hospital protocols as the new diagnostic standard.     

Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes.

In adults, endogenous hyperinsulinemic hypoglycemia is almost invariably due to insulinoma. In these patients with insulinoma, neuroglycopenic episodes exclusively after meal ingestion and negative 72-h fasts are extraordinarily rare. We describe five adults with neuroglycopenic episodes from hyperinsulinemic hypoglycemia within 4 h of meal ingestion and negative 72-h fasts. Each had negative transabdominal ultrasonography, spiral computed tomographic scanning, and celiac axis angiography of the pancreas. However, all showed positive selective arterial calcium stimulation tests indicative of pancreatic beta-cell hyperfunction. At pancreatic exploration, no insulinoma was detected by intraoperative ultrasonography and complete mobilization and palpation of the pancreas. Moreover, the resected pancreata showed islet hypertrophy and nesidioblastosis, but no insulinoma. No definite disease-causing mutation was detected in Kir6.2 and SUR1 genes, which encode the subunits of the pancreatic ATP-sensitive potassium channel responsible for glucose-induced insulin secretion. Four patients who underwent gradient-guided partial pancreatectomy have been free of hypoglycemic symptoms for up to 3 yr follow-up; the other, who underwent a limited distal pancreatectomy, has had brief recurrence of symptoms. The unique clinical features and responses to dynamic testing in these adults with hyperinsulinemic hypoglycemia in the absence of insulinoma may constitute a new syndrome of postprandial hypoglycemia from diffuse beta-cell hyperfunction.     

A ten-year material of insulinoma: diagnosis and surgical treatment.

A 10-year series of patients operated for insulinoma at Sahlgren's Hospital, Gothenburg, is presented. Twelve patients (three men, nine women) aged 26--70 years are included in the material. The patients had a history of recurrent hypoglycemic symptoms of 1 month to 20 years. Hyperinsulinism was established by determinations of blood glucose and plasma insulin in the fasting state. Selective angiography could show the tumor in 3 out of the 12 patients. A through pancreatic mobilization and palpation was performed during operation. Solitary pancreatic tumor was found in 10 patients, and 1 of them had also metastases in the liver. One patient had two tumors, one in the head and one in the tail of the pancreas. In one patient it was not possible to find any tumor at operation. Distal pancreatic resection and splenectomy were performed when the tumor was localized in the body or tail or when no tumor was found. Tumours in the head were excised locally. Microscopy showed insulinoma without malignancy in 10 patients, malignant tumor in insulae with metastases in the liver in 1 patient, and multiple adenomatosis of insulae in the patient without any palpable tumor. The 11 patients with benign disease were examined 1--10 years after the operation and had no signs of hyperinsulinism or of diabetes.