The first goal of treatment is to correct dehydration. Fluids are often given through a vein (intravenous fluids) to replace fluids lost in diarrhea.

The next goal is to slow the diarrhea. Some medications can help control diarrhea. Octreotide, which is a human-made form of the natural hormone somatostatin, blocks the action of VIP.

The best chance for a cure is surgery to remove the tumor. If the tumor has not spread to other organs, surgery can often cure the condition.

For metastatic disease, peptide receptor radionuclide therapy (PRRT) can be highly effective. This treatment involves attaching a radionuclide (Lutetium-177 or Yttrium-90) to a somatostatin analogue (octreotate or octreotide). This is a novel way to deliver high doses of beta radiation to kill tumours.

Some people seem to respond to a combination chemo called capecitabine and temozolomide but there is no report that it totally cured people from vipoma.

In general, treatment for PanNET encompasses the same array of options as other neuroendocrine tumors, as discussed in that main article. However, there are some specific differences, which are discussed here.

In functioning PanNETs, octreotide is usually recommended prior to biopsy or surgery but is generally avoided in insulinomas to avoid profound hypoglycemia.

PanNETs in MEN1 are often multiple, and thus require different treatment and surveillance strategies.

Some PanNETs are more responsive to chemotherapy than are gastroenteric carcinoid tumors. Several agents have shown activity. In well differentiated PanNETs, chemotherapy is generally reserved for when there are no other treatment options. Combinations of several medicines have been used, such as doxorubicin with streptozocin and fluorouracil (5-FU) and capecitabine with temozolomide. Although marginally effective in well-differentiated PETs, cisplatin with etoposide has some activity in poorly differentiated neuroendocrine cancers (PDNECs), particularly if the PDNEC has an extremely high Ki-67 score of over 50%.

Several targeted therapy agents have been approved in PanNETs by the FDA based on improved progression-free survival (PFS):

- everolimus (Afinitor) is labeled for treatment of progressive neuroendocrine tumors of pancreatic origin in patients with unresectable, locally advanced or metastatic disease. The safety and effectiveness of everolimus in carcinoid tumors have not been established.

- sunitinib (Sutent) is labeled for treatment of progressive, well-differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease. Sutent also has approval from the European Commission for the treatment of 'unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumors with disease progression in adults'. A phase III study of sunitinib treatment in well differentiated pNET that had worsened within the past 12 months (either advanced or metastatic disease) showed that sunitinib treatment improved progression-free survival (11.4 months vs. 5.5 months), overall survival, and the objective response rate (9.3% vs. 0.0%) when compared with placebo.

The definitive management is surgical removal of the insulinoma. This may involve removing part of the pancreas, as well (Whipple procedure and distal pancreatectomy).

Medications such as diazoxide and somatostatin can be used to block the release of insulin for patients who are not surgical candidates or who otherwise have inoperable tumors.

Streptozotocin is used in islet cell carcinomas which produce excessive insulin. Combination chemotherapy is used, either doxorubicin and streptozotocin, or fluorouracil and streptotozocin in patients where doxorubicin is contraindicated.

In metastasizing tumors with intrahepatic growth, hepatic arterial occlusion or embolization can be used.

Surgery can usually cure VIPomas. However, in one-third to one-half of patients, the tumor has spread by the time of diagnosis and cannot be cured.

These lesions rarely require surgery unless they are symptomatic or the diagnosis is in question. Since these lesions do not have malignant potential, long-term observation is unnecessary. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy.

Most patients with benign insulinomas can be cured with surgery. Persistent or recurrent hypoglycemia after surgery tends to occur in patients with multiple tumors. About 2% of patients develop diabetes mellitus after their surgery.

Although estimates vary, the annual incidence of clinically significant neuroendocrine tumors is approximately 2.5–5 per 100,000; two thirds are carcinoid tumors and one third are other NETs.

The prevalence has been estimated as 35 per 100,000, and may be considerably higher if clinically silent tumors are included. An autopsy study of the pancreas in people who died from unrelated causes discovered a remarkably high incidence of tiny asymptomatic NETs. Routine microscopic study of three random sections of the pancreas found NETs in 1.6%, and multiple sections identified NETs in 10%. As diagnostic imaging increases in sensitivity, such as endoscopic ultrasonography, very small, clinically insignificant NETs may be coincidentally discovered; being unrelated to symptoms, such neoplasms may not require surgical excision.

The treatment of choice for main-duct IPMNs is resection due to approximately 50% chance of malignancy. Side-branch IPMNs are occasionally monitored with regular CT or MRIs, but most are eventually resected, with a 30% rate of malignancy in these resected tumors. Survival 5 years after resection of an IPMN without malignancy is approximately 80%, 85% with malignancy but no lymph node spread and 0% with malignancy spreading to lymph nodes. Surgery can include the removal of the head of the pancreas (a pancreaticoduodenectomy), removal of the body and tail of the pancreas (a distal pancreatectomy), or rarely removal of the entire pancreas (a total pancreatectomy). In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy or robotic surgery. A study using Surveillance, Epidemiology, and End Result Registry (SEER) data suggested that increased lymph node counts harvested during the surgery were associated with better survival in invasive IPMN patients.

Even if the tumor has advanced and metastasized, making curative surgery infeasible, surgery often has a role in neuroendocrine cancers for palliation of symptoms and possibly increased lifespan.

Cholecystectomy is recommended if there is a consideration of long-term treatment with somatostatin analogs.

Disease progression is difficult to ascertain because the disease can metastasize anywhere in the body and can be too small to identify with any current technology. Markers of the condition such as chromogranin-A are imperfect indicators of disease progression.

For symptomatic relief of carcinoid syndrome:

- Octreotide (a somatostatin analogue which decreases the secretion of serotonin by the tumor and, secondarily, decreases the breakdown product of serotonin (5-HIAA))

- Telotristat ethyl (Xermelo) along with a somatostatin analogue in patients not responding to somatostatin analogue monotherapy. It is a tryptophan hydroxylase inhibitor and reduces the production of serotonin.

- Peptide receptor radionuclide therapy (PRRT) with lutetium-177, yttrium-90 or indium-111 labeled to octreotate is highly effective

- Methysergide maleate (antiserotonin agent but not used because of the serious side effect of retroperitoneal fibrosis)

- Cyproheptadine (an antihistamine drug with antiserotonergic effects)

Alternative treatment for qualifying candidates:

- Surgical resection of tumor and chemotherapy (5-FU and doxorubicin)

- Endovascular, chemoembolization, targeted chemotherapy directly delivered to the liver through special catheters mixed with embolic beads (particles that block blood vessels), used for patients with liver metastases.

There are no approved treatments for canine pancreatitis. Treatment for this disease is supportive, and may require hospitialization to attend to the dog's nutritional and fluid needs, pain management, and addressing any other disease processes (infection, diabetes, etc.) while letting the pancreas heal on its own. Treatment often involves "resting" the pancreas for a short period of time by nil per os/nothing per os (NPO)/nil by mouth (NBM), in which the patient receives no food or fluids by mouth, but is fed and hydrated by intravenous fluids and a feeding tube. Dehydration is also managed by the use of fluid therapy. However, a specialist from Texas A&M University has stated "There is no evidence whatsoever that withholding food has any beneficial effect." Other specialists have agreed with his opinion.

Canine pancreatitis is complex, often limiting the ability to approach the disease.

Risk factors for pancreatic adenocarcinoma include:

- Age, gender, and ethnicity; the risk of developing pancreatic cancer increases with age. Most cases occur after age 65, while cases before age 40 are uncommon. The disease is slightly more common in men than women, and in the United States is over 1.5 times more common in African Americans, though incidence in Africa is low.

- Cigarette smoking is the best-established avoidable risk factor for pancreatic cancer, approximately doubling risk among long-term smokers, the risk increasing with the number of cigarettes smoked and the years of smoking. The risk declines slowly after smoking cessation, taking some 20 years to return to almost that of non-smokers.

- Obesity; a BMI greater than 35 increases relative risk by about half.

- Family history; 5–10% of pancreatic cancer cases have an inherited component, where people have a family history of pancreatic cancer. The risk escalates greatly if more than one first-degree relative had the disease, and more modestly if they developed it before the age of 50. Most of the genes involved have not been identified. Hereditary pancreatitis gives a greatly increased lifetime risk of pancreatic cancer of 30–40% to the age of 70. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis on a research basis. Some people may choose to have their pancreas surgically removed to prevent cancer developing in the future.

- Chronic pancreatitis appears to almost triple risk, and as with diabetes, new-onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.

- Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in the Signs and symptoms section) new-onset diabetes may also be an early sign of the disease. People who have been diagnosed with Type 2 diabetes for longer than ten years may have a 50% increased risk, as compared with non-diabetics.

- Specific types of food (as distinct from obesity) have not been clearly shown to increase the risk of pancreatic cancer. Dietary factors for which there is some evidence of slightly increased risk include processed meat, red meat, and meat cooked at very high temperatures (e.g. by frying, broiling or barbecuing).

A recommend surveillance program for Multiple Endocrine Neoplasia Type 1 has been suggested by the International Guidelines for Diagnosis and Therapy of MEN syndromes group.

Apart from not smoking, the American Cancer Society recommends keeping a healthy weight, and increasing consumption of fruits, vegetables, and whole grains, while decreasing consumption of red and processed meat, although there is no consistent evidence this will prevent or reduce pancreatic cancer specifically. A 2014 review of research concluded that there was evidence that consumption of citrus fruits and curcumin reduced risk of pancreatic cancer, while there was possibly a beneficial effect from whole grains, folate, selenium, and non-fried fish.

In the general population, screening of large groups is not currently considered effective, although newer techniques, and the screening of tightly targeted groups, are being evaluated. Nevertheless, regular screening with endoscopic ultrasound and MRI/CT imaging is recommended for those at high risk from inherited genetics.

In 1982, IPMN was reported as a "mucin-producing tumor" by Kazuhiko Ohashi of the Japanese Foundation for Cancer Research.

A low fat diet is indicated. The use of drugs which are known to have an association with pancreatitis should be avoided. Some patients benefit from the use of pancreatic enzymes on a supplemental basis. One study indicated that 57 percent of dogs, who were followed for six months after an acute pancreatitis attack, either continued to exhibit inflammation of the organ or had decreased acinar cell function, even though they had no pancreatitis symptoms.

DNA mutation analysis in well-differentiated pancreatic neuroendocrine tumors identified four important findings:

- as expected, the genes mutated in NETs, MEN1, ATRX, DAXX, TSC2, PTEN and PIK3CA, are different from the mutated genes previously found in pancreatic adenocarcinoma.

- one in six well-differentiated pancreatic NETs have mutations in mTOR pathway genes, such as TSC2, PTEN and PIK3CA. The sequencing discovery might allow selection of which NETs would benefit from mTOR inhibition such as with everolimus, but this awaits validation in a clinical trial.

- mutations affecting a new cancer pathway involving ATRX and DAXX genes were found in about 40% of pancreatic NETs. The proteins encoded by ATRX and DAXX participate in chromatin remodeling of telomeres; these mutations are associated with a telomerase-independent maintenance mechanism termed ALT (alternative lengthening of telomeres) that results in abnormally long telomeric ends of chromosomes.

- ATRX/DAXX and MEN1 mutations were associated with a better prognosis.

Multiple endocrine neoplasia type 1 (MEN-1 syndrome) or Wermer's syndrome is part of a group of disorders, the multiple endocrine neoplasias, that affect the endocrine system through development of neoplastic lesions in pituitary, parathyroid gland and pancreas.

The most reliable test for EPI in dogs and cats is serum trypsin-like immunoreactivity (TLI). A low value indicates EPI. Fecal elastase levels may also be used for diagnosis in dogs.

In dogs, the best treatment is to supplement its food with dried pancreatic extracts. There are commercial preparations available, but chopped bovine pancreas from the butcher can also be used (pork pancreas should not be used because of the rare transmission of pseudorabies). Symptoms usually improve within a few days, but lifelong treatment is required to manage the condition. A rare side-effect of use of dried pancreatic extracts is oral ulceration and bleeding.

Because of malabsorption, serum levels of cyanocobalamin (vitamin B12) and tocopherol (vitamin E) may be low. These may be supplemented, although since cyanocobalamin contains the toxic chemical cyanide, dogs that have serious cobalamin issues should instead be treated with hydroxocobalamin or methylcobalamin. Cyanocobalamin deficiency is very common in cats with EPI because about 99 percent of intrinsic factor (which is required for cyanocobalamin absorption from the intestine) is secreted by the pancreas. In dogs, this figure is about 90 percent, and only about 50 percent of dogs have this deficiency. Cats may suffer from Vitamin K deficiencies. If there is bacterial overgrowth in the intestine, antibiotics should be used, especially if treatment is not working. In dogs failing to gain weight or continuing to show symptoms, modifying the diet to make it low-fiber and highly digestible may help. Despite previous belief that low-fat diets are beneficial in dogs with EPI, more recent studies have shown that a high-fat diet may increase absorption of nutrients and better manage the disease. However, it has been shown that different dogs respond to different dietary modifications, so the best diet must be determined on a case-by-case basis.

One possible sequela, volvulus (mesenteric torsion) is a rare consequence of EPI in dogs.

Heightened glucagon secretion can be treated with the administration of octreotide, a somatostatin analog, which inhibits the release of glucagon. Doxorubicin and streptozotocin have also been used successfully to selectively damage alpha cells of the pancreatic islets. These do not destroy the tumor, but help to minimize progression of symptoms.

The only curative therapy for glucagonoma is surgical resection, where the tumor is removed. Resection has been known to reverse symptoms in some patients.

A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in the overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor.

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome. It is caused by a progressive loss of the pancreatic cells that make digestive enzymes. Chronic pancreatitis is the most common cause of EPI in humans. Loss of digestive enzymes leads to maldigestion and malabsorption of nutrients.

Hemosuccus pancreaticus, also known as pseudohematobilia or Wirsungorrhage, is a rare cause of hemorrhage in the gastrointestinal tract. It is caused by a bleeding source in the pancreas, pancreatic duct, or structures adjacent to the pancreas, such as the splenic artery, that bleed into the pancreatic duct. Patients with hemosuccus may develop symptoms of gastrointestinal hemorrhage, such as blood in the stools, maroon stools, or melena. They may also develop abdominal pain. Hemosuccus pancreaticus is associated with pancreatitis, pancreatic cancer and aneurysms of the splenic artery. Angiography may be used to diagnose hemosuccus pancreaticus, where the celiac axis is injected to determine the blood vessel that is bleeding. Concomitant embolization of the end vessel may terminate the hemorrhage. Alternatively, a distal pancreatectomy may be required to stop the hemorrhage.

An adrenal tumor or adrenal mass is any benign or malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer is the presence of malignant adrenal tumors, and includes neuroblastoma, adrenocortical carcinoma and some adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but may cause significant health problems by unbalancing hormones.