Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing's syndrome, Basedow-Graves' disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.

Somatostatinoma is a tumour mainly originating from pancreas or duodenum; overall with an incidence of 1/40 million persons. We introduce a narrative review of literature of somatostatinoma including the relationship with neurofibromatosis type 1. Clinical presentation includes: Diabetes mellitus, cholelithiasis, steatorrhea, abdominal pain, and obstructive jaundice while papillary tumour may cause acute pancreatitis. The neoplasia may develop completely asymptomatic or it is detected as an incidental finding during an imaging or a surgical procedure. It may be sporadic or associated to genetic backgrounds especially for duodenal localisation as neurofibromatosis type 1 (NF1 gene with malfunction of RAS/MAPK pathway) or Pacak-Zhuang syndrome (EPAS1 gene encoding HIF). Surgery represents the central approach if feasible but the prognostic depends on location, and grading as indicated by WHO 2017 classification of neuroendocrine tumours. Previously known as Von Recklinghausen disease, neurofibromatosis type 1, the most frequent neurocutaneous syndrome, is an autosomal dominant disorder including: Café-au-lait spot, skin fold freckling on flexural zones, and neurofibromas as well as tumours such as gliomas of optic nerve, gastrointestinal stromal tumours (GISTs), iris hamartomas and brain tumours. Duodenal somatostatinoma is associated with the syndrome which actually involves more often a duodenal tumour of GIST type than a somatostatin secreting neoplasia. Other neuroendocrine tumours are reported: Gastrointestinal NENs at the level of rectum or jejunum and pheocromocytoma. Overall, one quarter of subjects have gastrointestinal tumours of different types. Somatostatinoma, when not located on pancreas but in duodenoum, may be registered in subjects with neurofibromatosis type 1 most probably in addition to other tumours. Overall, this type of neuroendocrine tumour with a challenging presentation has a poor prognosis unless adequate radical surgery is promptly offered to the patient.

Pancreatic neuroendocrine tumours (PanNETs) represent an uncommon type of pancreatic neoplasm, whose incidence is increasing worldwide. As per exocrine pancreatic cancer, a relationship seems to exist between PanNETs and glycaemic alterations. Diabetes mellitus (DM) or impaired glucose tolerance often occurs in PanNET patients as a consequence of hormonal hypersecretion by the tumour, specifically affecting glucose metabolism, or due to tumour mass effects. On the other hand, pre-existing DM may represent a risk factor for developing PanNETs and is likely to worsen the prognosis of such patients. Moreover, the surgical and/or pharmacological treatment of the tumour itself may impair glucose tolerance, as well as antidiabetic therapies may impact tumour behaviour and patients outcome. Differently from exocrine pancreatic tumours, few data are available for PanNETs as yet on this issue. In the present review, the bidirectional association between glycaemic disorders and PanNETs has been extensively examined, since the co-existence of both diseases in the same individual represents a further challenge for the clinical management of PanNETs.

Neuroendocrine tumors (NETs) constitute a large group of diverse neoplasms with a wide spectrum of clinical, imaging, and pathologic findings. Imaging diagnosis of NETs can be challenging, and several complementary imaging modalities may be needed during the diagnostic workup. Accurate interpretation of the imaging findings is important to facilitate diagnosis and contribute to patient management. This article discusses the gastrointestinal site-specific features and the tumor-specific features of several NETs and the role of several imaging modalities such as computed tomography, MR imaging, ultrasonography, and positron emission tomography in the evaluation of these NETs.

Somatostatinoma is a very rare neuroendocrine tumor that originates from D cells and accounts for less than 1% of all gastrointestinal endocrine tumors. The duodenum is the most frequent site for this tumor, followed by the pancreas. We here describe a 46-year-old Chinese woman who developed pancreatic somatostatinoma presenting with the characteristic "inhibitory" syndrome, but the symptoms were obscure and seemingly uncorrelated. This case is also unique for its large tumor size and mixed pathological pattern. Distal pancreatectomy was performed, and the patient has remained well since operation. As the syndromes of somatostatinoma may be obscure and atypical, clinicians should review all clinical findings to obtain an accurate diagnosis. Aggressive surgery is preferred to improve the survival.

Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

This article describes the appearance of miscellaneous cystic and endocrine neoplasms using magnetic resonance imaging (MRI). Magnetic resonance imaging is a useful diagnostic modality in the assessment of various pancreatic neoplasms. Pancreatic endocrine tumors are moderately low in signal intensity on T1-weighted fat-suppressed images and moderately high in signal intensity on T2-weighted fat-suppressed images and demonstrate homogeneous, ring, or diffuse heterogeneous enhancement on immediate postgadolinium gradient echo images. Cystic pancreatic neoplasms, including intraductal papillary mucinous neoplasm, are well demonstrated and subcategorized according to their characteristic cystic configurations on MRI and MR cholangiopancreatography images. Microcystic serous cystadenomas are demonstrated as a honeycombed appearance on T2-weighted images and have a central stellate scar. Mucinous cystic neoplasms usually appear as multilocular cystic masses, with benign forms of macrocystic tumors possessing uniform thickness septations and malignant forms exhibiting irregular septations and tumor nodules. The presence of tumor stroma, invasion of adjacent tissue, or liver metastases can be assessed by MRI. The connection between the pancreatic duct and the cystic tumor is usually well shown on MR cholangiopancreatography images.

Endocrine pancreatic tumors (EPTs) are uncommon, having an incidence of one per 100,000 people. They may appear as sporadic tumors or be associated with hereditary syndromes. EPTs are categorized as functioning or nonfunctioning tumors, based on the presence or absence of clinical syndromes. Among the former, insulinomas and gastrinomas are the most common. For the histopathological investigation of EPTs, chromogranin A and synaptophysin immunostainings are recommended. Measurement of circulating chromogranin A is also the cornerstone for the biochemical diagnosis of these tumors. Furthermore, specific hormones produced and released by the neoplastic cells can be identified by immunostaining and used for biochemical evaluation. To locate EPTs, both noninvasive (ultrasonography, computerized tomography, MRI and radionuclear imaging) and invasive techniques (arterial stimulation with venous sampling) can be used. Debulking procedures (surgery, radiofrequency ablation, embolization/chemoembolization and liver transplantation) and/or medical treatment (chemotherapy, biotherapy and peptide receptor radionuclide therapy) are the options available for the treatment of EPTs. Understanding the molecular events underlying the pathobiology of EPTs will aid the development of more accurate diagnostic/prognostic markers and give guidance for improved therapeutic modalities.

Glucagon-secreting endocrine pancreatic tumor is a rare disease, hence controlled studies on clinical management are lacking. In an attempt to assess the efficacy of diagnostic and therapeutic measures in patients with glucagonoma, a retrospective study was performed using the archives of a tertiary care center.

Records from 340 patients with endocrine pancreatic tumors were reassessed and 23 patients with malignant endocrine pancreatic tumor and elevated plasma glucagon levels were identified.

About 7% of patients with histologically verified tumors fullfilled our criteria for glucagonoma. Only 22% of these patients had developed diabetes prior to the diagnosis of glucagonoma. Seventy eight percent had metastatic disease to the liver at diagnosis. Necrolytic migratory erythema was diagnosed or clinically suspected in 52%. Somatostatin receptor scintigraphy was positive in 95%. Nineteen patients received chemotherapy at some point, in 18 cases streptozotocin and 5 FU. With this treatment, objective radiological responses were seen in 50% of evaluable patients. Other treatment modalities used were interferon, somatostatin analogs, hepatic artery embolization, radio-frequency ablation of liver metastases, and radiolabeled somatostatin analogs. During the study period, 11 patients died at a median of 80 months from diagnosis whereas 11 patients are still alive after a median follow up of 52 months. One patient was lost to follow-up.

Glucagonomas represent 7% of our comprehensive referral material of endocrine pancreatic tumors. Necrolytic migratory erythema was a common finding (52%) and diabetes less frequent at presentation than previously reported. Tumors were positive on somatostatin receptor scintigraphy and objective responses were seen to chemotherapy.

Pancreatic neuroendocrine tumours (PET) are rare neoplasms of the pancreas accounting for less than 5% of all primary pancreatic malignancies. Included in this group are insulinomas, gastrinomas, glucagonoma and somatostatinomas. Collectively these neoplasms are classified as functional PETs. Where a PET is not associated with a clinical syndrome due to hormone oversecretion, it is referred to as a non-functioning PET. Non-functioning PETs are pancreatic tumours with endocrine differentiation but lack a clinical syndrome of hormone hypersecretion. The incidence of these tumours varied between 15 and 53%. Presentation is related to the mass effect of the tumour with symptoms often non-specific. Treatment is surgical excision with chemotherapy and hormonal therapy is controversial. For functioning PETs, surgery remains the optimal therapy, however, long-term survival can be expected even in the presence of metastases. With advances in medical management, radiolabelled somatostatin therapy, hepatic arterial chemoembolisation and radiofrequency ablation, symptoms may be controlled to optimize quality of life.

We report a case of VIPoma in an 83-year-old female patient, who presented with frequent and excessive diarrhoea, muscle weakness, and severe hypokalaemia. Abdominal computed tomography (CT) revealed a 4x6 cm mass in the body of the pancreas. Laboratory analysis showed elevated levels of both vasoactive intestinal polypeptide (VIP; 153 pmol/l) and pancreatic polypeptide (161 pmol/l). In view of the patient's age, physical condition, and tumour size, surgical resection was not performed. The patient was treated with a long-acting octreotide, after which her symptoms diminished. After 24 months of follow-up, the patient remained in good physical condition without any further serious gastrointestinal symptoms. The VIPoma syndrome is caused by a neuroendocrine tumour, usually located in the pancreas, which secretes VIP, causing severe diarrhoea, dehydration and hypokalaemia. Treatment options include resection of the tumour, chemotherapy or the reduction of symptoms with somatostatin analogues. We provide an overview of the incidence, pathophysiology, diagnosis, treatment strategies, and prognosis of this rare syndrome.

MR imaging is a valuable tool in the assessment of the full spectrum of pancreatic diseases. MR imaging techniques are sensitive for the evaluation of pancreatic disorders in the following settings: (1) TI-weighted fat-suppressed and dynamic gadolinium-enhanced SGE imaging for the detection of chronic pancreatitis, ductal adeno-carcinoma, and islet-cell tumors; (2) T2-weighted fat-suppressed imaging and T2-weighted breath-hold imaging for the detection of islet-cell tumors;and (3) precontrast breath-hold SGE imaging for the detection of acute pancreatitis. Relatively specific morphologic and signal intensity features permit characterization of acute pancreatitis,chronic pancreatitis, ductal adenocarcinoma, insulinoma, gastrinoma, glucagonoma, microcystic cystadenoma, macrocystic cystadenoma, and solid and papillary epithelial neoplasm. MR imaging is effective as a problem-solving modality because it distinguishes chronic pancreatitis from normal pancreas and chronic pancreatitis with focal enlargement from pancreatic cancer in the majority of cases.MR imaging studies should be considered in the following settings: (1) in patients with elevated serum creatinine, allergy to iodine contrast, or other contraindications for iodine contrast administration; (2) in patients with prior CT imaging who have focal enlargement of the pancreas with no definable mass; (3) in patients in whom clinical history is worrisome for malignancy and in whom findings on CT imaging are equivocal or difficult to interpret; and (4) in situations requiring distinction between chronic pancreatitis with focal enlargement and pancreatic cancer. Patients with biochemical evidence of islet-cell tumors should be examined by MR imaging as the first-line imaging modality because of the high sensitivity of MR imaging for detecting the presence of islet-cell tumors and determining the presence of metastatic disease.

Somatostatin-producing endocrine tumors are rare neoplasms usually arising in the pancreas and duodenum and they account for less than 1% of all gastrointestinal endocrine tumors. Besides somatostatinoma syndrome, which is characterized by diabetes mellitus, steatorrhea and cholelithiasis, patients with somatostatin-producing endocrine tumors commonly complain of nonspecific symptoms such as vague abdominal pain, weight loss or changes in bowel habits. Tumor behavior cannot be predicted by histological features alone, and malignancy is determined by the presence of metastases. We report here a case of malignant pancreatic endocrine tumor producing somatostatin presented as relapsing cholangitis who was treated with Whipple pancreatoduodenectomy.

Surgical resection of insulinomas is the preferred treatment in order to avoid symptoms of hypoglycaemia. During the past years, advances in laparoscopic techniques have allowed surgeons to approach the pancreas and treat these lesions laparoscopically. We analysed the feasibility, safety, and outcome of patients undergoing laparoscopic resection of insulinomas in a large, retrospective, multicentre study.

Thirty-six patients with pancreatic insulinomas were enrolled in this study. All patients were suspected of having solitary insulinomas after preoperative localisation tests and underwent a laparoscopic approach. Patients, operating characteristics and outcome were analysed.

Mean patient age was 48 years (range 20-77 years). Insulinomas were localised in the head (n=7), isthmus (n=2), body (n=14) or tail (n=13) of the pancreas before laparoscopic approach. Mean size of the lesions was 15.5 mm (range 4-25 mm). The surgical procedure was enucleation in 19 cases (52%), spleen-preserving distal pancreatectomy in 12 cases (33%), spleno-pancreatectomy in three cases (8%), one duodenopancreatectomy and one central pancreatectomy. Conversion rate was 30%. The reason for conversion in seven patients (63%) was the inability to localise the tumour during the laparoscopic procedure. In six of these cases laparoscopic ultrasonography was not performed. Mean operating time was 156 min (range 50-420 min). Postoperative course was uneventful in 23 patients (64%). Eleven patients (30%) developed specific complications of pancreatic surgery: intra-abdominal abscess (n=6) or pancreatico-cutaneous fistula (n=5). Mean duration of fistulae was 55 days (range 5-130 days) and all the fistulae were dry at follow-up. After a mean follow-up period of 26 months (range 2-87 months), 33 patients (91%) are free of symptoms, and three patients have been lost to follow-up.

The laparoscopic approach is safe to treat preoperatively localised insulinoma, with a morbidity rate comparable to that for the open approach. When the tumour is not found during laparoscopy, laparoscopic ultrasonography seems to be the most efficient tool to localise it and probably to prevent conversion.

Necrolytic migratory erythema (NME) is a cutaneous manifestation of the glucagonoma syndrome. We present a case with a pancreatic glucagon-secreting tumour, skin eruption and a good response to treatment.

Neuroendocrine tumors of the pancreas are rare neoplasms arising predominantly from the pancreatic islets of Langerhans and are thus known as islet cell tumors. More than the half of all neuroendocrine tumors are called functioning islet cell tumors because they secrete one or more biologically active peptides that may produce clinical symptoms. Clinical diagnosis of non-functioning, i.e., biologically inactive, tumors is often delayed and patients tend to present with advanced tumors (size greater than 5 cm) that are easily localized by using conventional imaging modalities. On the other hand, symptoms of functioning islet cell tumors usually appear early in the clinical course, rendering the preoperative localization of these small hormone-producing tumors (size less than 2 cm) difficult with non-invasive methods. Since functioning islet cell tumors can often be cured by surgical resection, invasive procedures are warranted when necessary for localization diagnosis. Failure to search for, detect, and resect these small tumors will invariably result in persistent symptoms. Regarding the unsatisfactory results of morphological imaging methods, functional studies, especially arterial stimulation with hepatic venous samplings, may provide a preoperative regionalization of the pancreatic adenoma, regardless of its size.

Glucagonomas are rare functional endocrine tumors of the pancreas that classically present with symptoms of glucagon excess, including rash, hyperglycemia, diarrhea, and weight loss. Metastatic disease at presentation is common but is often limited to the liver and regional lymph nodes. We describe an unusual case of a patient with glucagonoma who presented with a pathologic vertebral fracture. This tumor had no evidence of active hormone secretion but tested positive for glucagon by immunohistochemical staining.

Pancreatic carcinoids are very rare and usually have a poor prognosis. We describe a case of a pancreatic carcinoid with liver micrometastases in a female of 54 years of age in whom the tumor was without pronounced symptoms apart from rare episodes of flushing. The patient had been treated since November 1995 with the somatostatin analogue octreotide 200 micrograms twice daily for the first 2 years, with the long-acting analogue lanreotide 30 mg every 10 days for the following year, and then with octreotide LAR 20 mg every 28 days until the present. The flushing episodes disappeared completely, and the patient was well. Moreover, the dimensions of the tumor and the liver micrometastases remained stable during the observation period. As far as we known, this is the first case of a pancreatic carcinoid treated successfully with somatostatin analogues and having a satisfactory prognosis.

Somatostatinomas are the rarest pancreatic endocrine tumors and can arise in the pancreas or duodenum. Duodenal somatostatinomas are less common than, and are distinguished from, their pancreatic counterparts by a frequent association with type I neurofibromatosis, the presence of psammoma bodies, the less frequent presence of metastatic disease, and the absence of somatostatinoma syndrome (diabetes mellitus, steatorrhea, and cholelithiasis). We report a case of somatostatinoma with metastases and psammoma bodies presenting with all three features of the syndrome in a patient with neurofibromatosis. Although several reports have documented portions of the syndrome in patients with duodenal somatostatinomas, to our knowledge, this is the first report of the complete syndrome associated with a duodenal lesion.

Because of the diverse nature of endocrine organs, and their vast range of physiologic functions, endocrine tumors encompass a wide range of origination sites and disease entities. The clinical picture of affected individuals is highly dependent on the tissue of origin, and the presence or absence of functional hormone secretions. Identification, localization, and therapeutic strategies, as well as prognosis can vary greatly. Many endocrine tumors have been described in human as well as veterinary patients. This article focuses on endocrine tumors of dogs and cats. Various tumors affecting the pancreas, thyroid, parathyroid, adrenal and pituitary glands are described, including insulinoma, gastrinoma, glucagonoma, and thyroid carcinoma, as well as parathyroid hormone- and growth hormone-secreting tumors. The syndrome of multiple endocrine neoplasia is also described.

Pancreatic endocrine tumours (PET) are rare but nonetheless important to recognize and treat in a timely fashion. Significant morbidity occurs due to excess secretion of hormones, with all of the PET having some degree of malignant potential. Surgeons must plan directed operative strategies to deal with these tumours and be prepared to undertake aggressive palliative debulking resections if indicated. Somatostatin receptor scintigraphy and endoscopic ultrasound have been particularly helpful in both localizing and staging patients with PET. Other important advances in management include the use of long-acting somatostatin analogues to inhibit hormonal secretion and tumour growth. The possibility of multiple endocrine neoplasia type 1 (MEN-1) should be considered in any patient with a PET. The present article will review the various classes of PET, describe MEN-1 in relation to PET and examine advances in imaging and localization. The role of surgery for PET is also discussed in the present review.

Glucagonoma syndrome is a paraneoplastic phenomenon characterized by an islet alpha-cell pancreatic tumor, necrolytic migratory erythema, diabetes mellitus, weight loss, anemia, stomatitis, thromboembolism, and gastrointestinal and neuropsychiatric disturbances. These clinical findings in association with hyperglucagonemia and demonstrable pancreatic tumor establish the diagnosis. Glucagon itself is responsible for most of the observed signs and symptoms, and its induction of hypoaminoacidemia is thought to lead to necrolytic migratory erythema. Liver disease and fatty acid and zinc deficiency states may also contribute to the pathogenesis of the eruption in some cases. Most patients are diagnosed too late in the clinical course for cure, but successful palliation of symptomatology can usually be achieved with surgical and medical intervention. This paper reviews the glucagonoma syndrome, paying particular attention to its cutaneous features, and provides new perspectives in our current understanding of this phenomenon.

NETs of pancreas are rare and may or may not be associated with symptoms of hormone overproduction. Treatment is required for control of tumor growth and for relief of symptoms associated with excess hormone. With advances in the nonsurgical management of many hormone-related symptoms (e.g., proton pump inhibitors or somatostatin analogues), care for many of these patients has shifted toward the control of tumor progression. Complete surgical resection is the only curative treatment for these tumors. With improvements in the preoperative imaging and intraoperative localization techniques, it is hoped that these tumors will be identified and resected for cure with increased frequency. For patients with hepatic metastasis, initial expectant observation and medical management of symptoms is appropriate in view of the long and indolent course of the disease. Hepatic arterial embolization is the preferred mode of palliation for pain and hormonal symptoms. A curative hepatic resection may be possible in selected patients.

A 37-year-old male patient with no significant past medical history presented with a 6-month history of intermittent epigastric pain which was partially relieved by antacid medication. Gastroscopy showed a peptic ulcer and the biopsies that were taken did not show signs of malignancy. Conservative treatment was initiated, but healing was prolonged, and the epigastric pain persisted. The patient was referred to our department for further diagnosis.

The first goal of therapy is the control of gastric acid hypersecretion using PPIs or high-dose H2R antagonists. The diagnosis of Multiple Endocrine Neoplasia (MEN I) should be established early in the disease. Localization of gastrinoma tumor should be performed using a combination of endoscopic ultrasonography (EUS), somatostatin receptor scintigraphy (SRS), and computerized tomography (CT), or Magnetic Resonance Imaging (MRI). Surgical resection in sporadic ZES should be performed to attempt cure of tumor. Surgery, hormonal, chemotherapy, embolization therapy or therapeutic OctreoScan should be considered in patients with metastatic tumor.

Carcinoid somatostatinoma is a rare neuroendocrine malignant tumour and the duodenal location is an atypical site of presentation of which only few cases have been reported in the literature. A case of duodenal carcinoid somatostatinoma metastatic to lymph nodes in a 66-year-old patient is presented with an update of the literature. No relevant signs or symptoms were associated to the retrogastric lymph-node mass, which deformed but did not infiltrate the stomach wall. At the first and third portion of the duodenum, two polipoid endoluminal nodules (size 1 cm) were found with adjacent adenopathy partially adherent to the head of the pancreas and with thickening of the antropyloric wall. The patient underwent antrectomy duodenum mobilization and lymphadenectomy in the hepatic artery region. The treatment was successful and, over 3 years after diagnosis, there has been no clinical or radiological evidence of relapse. Duodenal somatostatinoma is rare and its diagnosis is often incidental. Surgery would be the appropriate treatment in the early stage of the disease with good chances of cure.

The diagnosis of a pancreatic carcinoid should be based on the measurement of serotonin in serum or its demonstration in the tumor and/or by the measurement of its derivative (5-HIAA) in urine. Carcinoid of the pancreas is a rare but definite entity; usually having metastasized by the time of diagnosis. The term "serotonin-producing tumor of the pancreas" has been suggested as an alternative designation for "pancreatic carcinoid."

The literature on carcinoid tumors of the pancreas is confusing because much of it preceded the development of the more specific immunological, chemical and staining techniques currently available.

43 case reports were collected from the world's literature, based on a demonstrable pancreatic neuroendocrine tumor plus a positive finding of at least one of the following without another dominant hormone being demonstrated: elevation of 5-Hydroxytryptamine (5-HT) (serotonin) in the serum or detected in tumor tissue, and/or elevation of 5-Hydroxyindole acetic acid (5-HIAA) in the urine. In addition to these two hormone-specific assays, information was collected on the silver-staining properties of the tumor; properties which have traditionally been associated with carcinoid tumors. Positive silver staining in tumor cells (argyrophilic and/or argentaffin reaction) is strongly indicative of the carcinoid tumor but the findings are less specific than the hormone assays and immunohistologic stains.

In this review of 43 cases, including two current ones, the pancreatic carcinoid tumor has the following important features: 1. It is a rare tumor that is usually diagnosed late when the tumor is large and has metastasized. Thirty-eight (88.4%) have been malignant. They are, therefore, associated with a high incidence of the "carcinoid syndrome." 2. To date, prognosis in therapy is poor, based on delayed diagnosis, a resultant low incidence of resectability, and an uncertain duration of survival after resection. 3. Pancreatic carcinoid tumors remain difficult to differentiate from other endocrine tumors. The measurement of urinary 5-HIAA excretion or the demonstration of elevated serotonin level in the tumor or in serum is essential to its distinction. Silver staining of the tumor, although of historic importance, has been superceded by the hormone-specific studies. 4. To distinguish it from other endocrine tumors of the pancreas, the terms "pancreatic serotoninoma" or "serotonin-producing tumor of the pancreas" have been suggested as possible alternatives. Its growth characteristics may be related more to its cell of origin than to its extent of hormone secretion. Not all of the tumors result in recognizable hyperserotoninemia.

VIP-secreting tumours are rare, but they produce a dramatic clinical picture, the most prominent feature being profuse, watery diarrhoea and hypokalaemia. VIPomas are malignant and require sophisticated diagnostic and localization techniques in order to identify their presence. Delays in diagnosis are the rule rather than the exception. Improvements in the diagnosis of VIPomas appear to result in an increase in resectability rates. A definitive diagnosis is aided by the determination of plasma VIP concentrations through the use of sensitive radioimmunoassays. With heightened awareness of this syndrome, increasing numbers of patients can be identified and more effective treatments developed for the refractory and recurrent tumours.

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.

Pancreatic endocrine neoplasms are a heterogeneous group of tumors that produce active hormones and result in distinct clinical syndromes. For the most part, they are malignant and require sophisticated diagnostic and localization techniques in order to identify their presence. Delays in diagnosis are the rule rather than the exception. Improvements in the diagnosis of gastrinomas and insulinomas appear to result in an increase in resectability rates. The widespread availability of intraoperative ultrasonography, as well as improved knowledge of the location of these tumors, has also had an impact on improved cure rates. With heightened awareness of these syndromes, increasing numbers of patients can be identified and more effective treatments developed for the refractory and recurrent tumors.

A 69-year-old woman presented with a single enlarged lymph node in the left axilla. Clinical examination and other investigations, including various imaging methods, failed to reveal the primary tumour. However, indium-111 pentetreotide scan revealed a site of uptake in the anterior region of the left thorax. Peroperative imaging with 111In-pentetreotide confirmed the tumour uptake and use of a nuclear surgical probe allowed precise localization of the tumour, which was completely resected.