Glucagonoma

Glucagonomas are neuroendocrine tumors (NETs) of pancreas, derived from alpha islet cells. They represent around 1% of all pancreatic NETs. These tumors often associated with a well-described glucagonoma syndrome characterized with hyperglucagonemia, skin rash, glucose intolerance, hypoalbuminemia, weight loss, and normochromic normocytic anemia. Glucagonomas may present as a part the multiple endocrine neoplasia syndrome type 1 (MEN 1). They are usually encapsulated firm nodules varying in size from several mms up to 25 cm. The tail of pancreas is predominantly involved. The tumors consist of cords and nests of well-differentiated islet cells. Despite their benign histologic appearance and slow growth rate such as low mitotic index and uncommon nuclear atypia, most pancreatic glucagonomas are malignant with high metastatic potential. Necrolytic migratory erythema (NME) and mild diabetes are the predominant signs of the glucagonoma syndrome. Glucagonomas predominantly metastasize to the liver and adjacent lymph nodes, less frequently to the vertebra, ovary, peritoneum, and adrenals. Glucagonoma is often diagnosed relatively late in the course of the disease since many of the symptoms are nonspecific. NME is the most important manifestation of the disease, which leads to diagnosis of glucagonoma but it is not pathognomonic. Diagnosis rests on demonstrating a pathological elevation of the plasma glucagon concentration. Pancreatic polipeptide (PP) and chromogranin A (CgA) are frequently elevated in glucagonoma syndrome. Abdominal computerized tomography (CT) is usually adaquate for diagnosis; however, magnetic resonance (MR) imaging, selective angiography, or endoscopic ultrasonography (EUS) may also needed. Peptide receptor imaging has been developed successfully for visualization of somatostatin receptors on NETs. Surgery is the only curative therapeutic option. The cure potential is as low as 5%. Control of liver metastases by metastasectomy, microwave ablation, radiofrequency ablation (RFA) or chemoembolization/radioembolization or stereotactic radiotherapy. The morbidity associated with glucagonomas results principally from the hormonal syndrome. The conventional chemotherapy for glucagonomas and pancreatic endocrine tumors is 5-flourouracil or adriamycin and streptozocin or the combination of the three drugs altogether, that is FAS regimen. Temozolomide in combination with capecitabine has been found to be effective on P-NETs. Two molecularly targeted agents, an oral tyrosine kinase inhibitor (TKI) sunitib and everolimus, an inhibitor of mammalian target of rapamycin (mTOR) have been approved in the treatment of metastatic P-NETs. Somatostatin analogues (SSA) have been shown to effectively control symptoms resulting from excessive hormone release in patients with carcinoid, Verner–Morrison syndrome, and glucagonoma syndromes. The 10-year survival rate in patients with diabetico-dermatological syndrome (DDS) was 51.6% in those with metastases and 64.3% in those without metastases.