Evaluation and Treatment of Somatostatinoma

What is a somatostatinoma?

Somatostatinoma is a very rare neuroendocrine tumor, with an incidence of one in 40 million persons. They occur more frequently in female patients (67%). The median age at diagnosis is 51 years (range 26-84 years). These tumors arise from the delta cells in the pancreas, although these cells can be present in duodenal tissue as well, where 38% of the tumors occur. Exceedingly rare, a jejunal somatostatinoma has been reported. Metastases are present in 77 % of patients at diagnosis (liver 42%, lymph nodes 39 %).

Somatostatin is a normally occurring peptide that inhibits the function of almost all gut hormones. Diabetes occurs in 95% of patients caused by the suppression of insulin. Cholelithiasis occurs in 94% of patients caused by the inhibition of cholecystokinin and reduced gallbladder motility. Less common presenting symptoms are steatorrhea and hypochlorydia (86%) and result from inhibition of pancreatic enzymes, bicarbonate, intestinal absorption and suppression of gastrin. Hypoglycemia may result from inhibition of glucagon. The large spectrum of symptoms explain why the lesions are sometimes diagnosed accidentally when performing studies for other diseases, or during laparotomy/laparoscopy for cholelithiasis or adrenal lesions.

Pancreatic tumors tend to be larger than duodenal tumors, with a median size being greater than 4 cm, while most duodenal tumors are less than 2 cm at diagnosis. Unlike insulinomas and gastrinomas, which tend to become symptomatic due to hormone overproduction at smaller sizes, it is thought that symptoms of somatostatinoma due to hormone excess only occur with very high hormone levels, and, therefore, with large tumors.

About 50% of patients with somatostatinoma may have relation to other endocrine disorders, particularly those presenting with duodenal tumors. Neurofibromatosis type-1 (NF-1), and less frequently conditions such as MEN-1, von Hippel-Lindau disease, tuberous sclerosis, and gastrointestinal stromal tumors (GIST) have presented with somatostatinoma as well. Tumor markers, with the exception of somatostatin, are nonspecific, and include pancreatic polypeptide, ghrelin, neuron-specific enolase, and chromogranin A.

Most somatostatinomas are diagnosed by radiographic imaging studies, such as CT scan, in the work-up of unexplained abdominal pain; or by endoscopy for unexplained blood loss and/or diarrhea. Somatostatinomas are frequently polysecretant lesions, particularly those of pancreatic origin. PET scan and somatostatin receptor scintigraphy also may localize these tumors. 

What is the treatment of somatostatinoma?

Since somatostatinomas have a high malignant potential, aggressive intervention is warranted. Surgical excision offers the only opportunity for long-term cure. Five year survival approaches 100% following complete resection in the absence of metastatic disease, while five year survival in the range of 60% overall is seen in patients with metastatic disease at diagnosis. Resection strategies may include distal subtotal pancreatectomy, pancreaticoduodenectomy (Whipple procedure), or, for smaller duodenal tumors, local excision. These tumors tend to be slow growing, and debulking of extensive disease may offer symptomatic relief and extend survival.

Are somatostatinomas hereditary?

As previously mentioned, somatostatinomas may occur concomitantly with other endocrine hereditary entities in up to 50% of patients. They occur less rarely in patients with neurofibromatosis (NF-1) than sporadic cases. NF-1 is one of the more common familial tumor syndromes. It is autosomal dominant, and occurs related to a genetic mutation of what is thought to be a tumor suppressor gene on chromosome 17. Tumors in NF-1 may involve both nervous and non-nervous system tissues. In adults, pheochromocytomas, GIST, breast cancer, and less commonly, somatostatinomas may occur in addition to the obvious neurofibromas. Somatostatinomas have rarely been associated with other disorders, such as von Hippel-Lindau disease. Somatostatinomas in NF-1 are much more likely to be duodenal in origin.