CT-scans, MRIs, sonography (ultrasound), and endoscopy (including endoscopic ultrasound) are common diagnostic tools. CT-scans using contrast medium can detect 95 percent of tumors over 3 cm in size, but generally not tumors under 1 cm.

Advances in nuclear medicine imaging, also known as molecular imaging, has improved diagnostic and treatment paradigms in patients with neuroendocrine tumors. This is because of its ability to not only identify sites of disease but also characterize them. Neuronedocrine tumours express somatostatin receptors providing a unique target for imaging. Octreotide is a synthetic modifications of somatostatin with a longer half-life. OctreoScan, also called somatostatin receptor scintigraphy (SRS or SSRS), utilizes intravenously administered octreotide that is chemically bound to a radioactive substance, often indium-111, to detect larger lesions with tumor cells that are avid for octreotide.

Somatostatin receptor imaging can now be performed with positron emission tomography (PET) which offers higher resolution, three-dimensional and more rapid imaging. Gallium-68 receptor PET-CT is much more accurate than an OctreoScan.

Imaging with fluorine-18 fluorodeoxyglucose (FDG) PET may be valuable to image some neuroendocrine tumors. This scan is performed by injected radioactive sugar intravenously. Tumors that grow more quickly use more sugar. Using this scan, the aggressiveness of the tumor can be assessed.

The combination of somatostatin receptor and FDG PET imaging is able to quantify somatostatin receptor cell surface (SSTR) expression and glycolytic metabolism, respectively. The ability to perform this as a whole body study is highlighting the limitations of relying on histopathology obtained from a single site. This is enabling better selection of the most appropriate therapy for an individual patient.

The insulinoma might be localized by noninvasive means, using ultrasound, CT scan, or MRI techniques. An indium-111 pentetreotide scan is more sensitive than ultrasound, CT, or MRI for detection of somatostatin receptor positive tumors, but not a good diagnostic tool for insulinomas. An endoscopic ultrasound has a sensitivity of 40-93% (depending on the location of the tumor) for detecting insulinomas.

Sometimes, angiography with percutaneous transhepatic pancreatic vein catheterization to sample the blood for insulin levels is required. Calcium can be injected into selected arteries to stimulate insulin release from various parts of the pancreas, which can be measured by sampling blood from their respective veins. The use of calcium stimulation improves the specificity of this test.

During surgery to remove an insulinoma, an intraoperative ultrasound can sometimes localize the tumor, which helps guide the surgeon in the operation and has a higher sensitivity than noninvasive imaging tests.

Intraductal papillary mucinous neoplasms can come to clinical attention in a variety of different ways. The most common symptoms include abdominal pain, nausea and vomiting. The most common signs patients have when they come to medical attention include jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), weight loss, and acute pancreatitis. These signs and symptoms are not specific for an intraductal papillary mucinous neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have an intraductal papillary mucinous neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal dilatation of the pancreatic duct or one of the branches of the pancreatic duct. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

IPMN forms cysts (small cavities or spaces) in the pancreas. These cysts are visible in CT scans (X-ray computed tomography). However, many pancreatic cysts are benign (see Pancreatic disease).

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (i.e. undergoing an ultrasound, CT or MRI scan) for another reason. Up to 6% of patients undergoing pancreatic resection did so for treatment of incidental IPMNs.

In 2011, scientists at Johns Hopkins reported that they have developed a gene-based test that can be used to distinguish harmless from precancerous pancreatic cysts. The test may eventually help patients with harmless cysts avoid needless surgery. Bert Vogelstein and his colleagues discovered that almost all of the precancerous cysts (intraductal papillary mucinous neoplasms) of the pancreas have mutations in the KRAS and/or the GNAS gene. The researchers then tested a total of 132 intraductal papillary mucinous neoplasms for mutations in KRAS and GNAS. Nearly all (127) had mutations in GNAS, KRAS or both. Next, the investigators tested harmless cysts such as serous cystadenomas, and the harmless cysts did not have GNAS or KRAS mutations. Larger numbers of patients must be studied before the gene-based test can be widely offered.

Serous cystic neoplasms can come to clinical attention in a variety of ways. The most common symptoms are very non-specific and include abdominal pain, nausea and vomiting. In contrast to many of the other tumors of the pancreas, patients rarely develop jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), or weight loss. These signs and symptoms are not specific for a serous cystic neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests.

Once a doctor has reason to believe that a patient may have serous cystic neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal a cystic mass within the pancreas. The cysts do not communicate with the larger pancreatic ducts. In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning.

A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason.

The 2010 WHO classification of tumors of the digestive system grades all the neuroendocrine tumors into three categories, based on their degree of cellular differentiation (from well-differentiated "NET G1" through to poorly-differentiated "NET G3"). The NCCN recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the stage by stage outcomes for PanNETs are dissimilar to pancreatic exocrine cancers. A different TNM system for PanNETs has been proposed by The European Neuroendocrine Tumor Society.

Normally, endogenous insulin production is suppressed in the setting of hypoglycemia. A 72-hour fast, usually supervised in a hospital setting, can be done to see if insulin levels fail to suppress, which is a strong indicator of the presence of an insulin-secreting tumor.

Symptoms from secreted hormones may prompt measurement of the corresponding hormones in the blood or their associated urinary products, for initial diagnosis or to assess the interval change in the tumor. Secretory activity of the tumor cells is sometimes dissimilar to the tissue immunoreactivity to particular hormones.

Given the diverse secretory activity of NETs there are many other potential markers, but a limited panel is usually sufficient for clinical purposes. Aside from the hormones of secretory tumors, the most important markers are:

- chromogranin A (CgA), present in 99% of metastatic carcinoid tumors

- urine 5-hydroxyindoleacetic acid (5-HIAA)

- neuron-specific enolase (NSE, gamma-gamma dimer)

- synaptophysin (P38)

Newer markers include N-terminally truncated variant of Hsp70 is present in NETs but absent in normal pancreatic islets. High levels of CDX2, a homeobox gene product essential for intestinal development and differentiation, are seen in intestinal NETs. Neuroendocrine secretory protein-55, a member of the chromogranin family, is seen in pancreatic endocrine tumors but not intestinal NETs.

Management of MEN2 patients includes thyroidectomy including cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved and selective resection of pathologic parathyroid glands for primary hyperparathyroidism.

Familial genetic screening is recommended to identify at risk subjects who will develop the disease, permitting early management by performing prophylactic thyroidectomy, giving them the best chance of cure.

Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC indicating the necessity of a complete thyroid surgery for index cases with MTC and the early thyroidectomy for screened at risk subjects.

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.

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.

An adrenal "incidentaloma" is an adrenal tumor found by coincidence without clinical symptoms or suspicion. It is one of the more common unexpected findings revealed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasonography.

In these cases, a dexamethasone suppression test is often used to detect cortisol excess, and metanephrines or catecholamines for excess of these hormones. Tumors under 3 cm are generally considered benign and are only treated if there are grounds for a diagnosis of Cushing's syndrome or pheochromocytoma. Radiodensity gives a clue in estimating malignancy risk, wherein a tumor with 10 Hounsfield units or less on an unenhanced CT is probably a lipid-rich adenoma.

Hormonal evaluation includes:

- 1-mg overnight dexamethasone suppression test

- 24-hour urinary specimen for measurement of fractionated metanephrines and catecholamines

- Blood plasma aldosterone concentration and plasma renin activity, "if hypertension is present"

On CT scan, benign adenomas typically are of low radiographic density (due to fat content) and show rapid washout of contrast medium (50% or more of the contrast medium washes out at 10 minutes). If the hormonal evaluation is negative and imaging suggests benign, followup should be considered with imaging at 6, 12, and 24 months and repeat hormonal evaluation yearly for 4 years

Before gene testing was available, the type and location of tumors determined which type of MEN2 a person had. Gene testing now allows a diagnosis before tumors or symptoms develop.

A table in the multiple endocrine neoplasia article compares the various MEN syndromes. MEN2 and MEN1 are distinct conditions, despite their similar names. MEN2 includes MEN2A, MEN2B and familial medullary thyroid cancer (FMTC).

The common feature among the three sub-types of MEN2 is a high propensity to develop medullary thyroid carcinoma.

The 2010 WHO classification of tumors of the digestive system grades all the pancreatic neuroendocrine tumors (PanNETs) into three categories, based on their degree of cellular differentiation (from "NET G1" through to the poorly differentiated "NET G3"). The U.S. National Comprehensive Cancer Network recommends use of the same AJCC-UICC staging system as pancreatic adenocarcinoma. Using this scheme, the stage-by-stage outcomes for PanNETs are dissimilar to those of the exocrine cancers. A different TNM system for PanNETs has been proposed by the European Neuroendocrine Tumor Society.

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.

Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor, which is usually metastatic at presentation.

Tests include:

- Blood chemistry tests (basic or comprehensive metabolic panel)

- CT scan of the abdomen

- MRI of the abdomen

- Stool examination for cause of diarrhea and electrolyte levels

- Vasoactive intestinal peptide (VIP) level in the blood

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.

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.

Treatment is by chemotherapy with streptozocin, dacarbazine, doxorubicin or by 'watchful waiting' and surgical debulking via Whipple procedure and other resections of the gastrointestinal organs affected.

The diagnosis of SCLC, TC and AC can be made by light microscopy without the need for special tests in most cases, but for LCNEC it is required to demonstrate NE differentiation by immunohistochemistry or electron microscopy.

Genetic changes are very high in SCLC and LCNEC, but usually low for TC, intermediate for AC.

Pituitary incidentalomas are pituitary tumors that are characterized as an incidental finding. They are often discovered by computed tomography (CT) or magnetic resonance imaging (MRI), performed in the evaluation of unrelated medical conditions such as suspected head trauma, in cancer staging or in the evaluation of nonspecific symptoms such as dizziness and headache. It is not uncommon for them to be discovered at autopsy. In a meta-analysis, adenomas were found in an average of 16.7% in postmortem studies, with most being microadenomas (<10mm); macrodenomas accounted for only 0.16% to 0.2% of the decedents. While non-secreting, noninvasive pituitary microadenomas are generally considered to be literally as well as clinically benign, there are to date scant studies of low quality to support this assertion.

It has been recommended in the current Clinical Practice Guidelines (2011) by the Endocrine Society - a professional, international medical organization in the field of endocrinology and metabolism - that all patients with pituitary incidentalomas undergo a complete medical history and physical examination, laboratory evaluations to screen for hormone hypersecretion and for hypopituitarism. If the lesion is in close proximity to the optic nerves or optic chiasm, a visual field examination should be performed. For those with incidentalomas which do not require surgical removal, follow up clinical assessments and neuroimaging should be performed as well follow-up visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm and follow-up endocrine testing for macroincidentalomas.

The diagnosis can be established by measuring catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection. Care should be taken to rule out other causes of adrenergic (adrenalin-like) excess like hypoglycemia, stress, exercise, and drugs affecting the catecholamines like stimulants, methyldopa, dopamine agonists, or ganglion blocking antihypertensives. Various foodstuffs (e.g. coffee, tea, bananas, chocolate, cocoa, citrus fruits, and vanilla) can also affect the levels of urinary metanephrine and VMA (vanillylmandelic acid).

Imaging by computed tomography or a T2 weighted MRI of the head, neck, and chest, and abdomen can help localize the tumor. Tumors can also be located using an MIBG scan, which is scintigraphy using iodine-123-marked metaiodobenzylguanidine. Even finer localization can be obtained in certain PET scan centers using PET-CT or PET-MRI with [18F] fluorodopamine or FDOPA.

Pheochromocytomas occur most often during young-adult to mid-adult life.

These tumors can form a pattern with other endocrine gland cancers which is labeled multiple endocrine neoplasia (MEN). Pheochromocytoma may occur in patients with MEN 2 and MEN 3 (MEN 2B). Von Hippel Lindau patients may also develop these tumors.

Patients experiencing symptoms associated with pheochromocytoma should be aware that it is rare. However, it often goes undiagnosed until autopsy; therefore patients might wisely choose to take steps to provide a physician with important clues, such as recording whether blood pressure changes significantly during episodes of apparent anxiety.

Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.

Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia.

From a pathology perspective, several tumors need to be considered in the differential diagnosis, including paraganglioma, ceruminous adenoma, metastatic adenocarcinoma, and meningioma.

Surgery, if feasible, is the only curative therapy. If the tumor has metastasized (most commonly, to the liver) and is considered incurable, there are some promising treatment modalities, such as radiolabeled octreotide (e.g. Lutetium (Lu) DOTA-octreotate) or the radiopharmaceutical 131I-mIBG (meta iodo benzyl guanidine) for arresting the growth of the tumors and prolonging survival in patients with liver metastases, though these are currently experimental.

Chemotherapy is of little benefit and is generally not indicated. Octreotide or Lanreotide (somatostatin analogues) may decrease the secretory activity of the carcinoid, and may also have an anti-proliferative effect. Interferon treatment is also effective, and usually combined with somatostatin analogues.

As the metastatic potential of a coincidental carcinoid is probably low, the current recommendation is for follow up in 3 months with CT or MRI, labs for tumor markers such as serotonin, and a history and physical, with annual physicals thereafter.