Somatostatinoma syndrome

Overview

Somatostatinoma syndrome is a rare clinical condition caused by a somatostatinoma — a neuroendocrine tumor that secretes excessive amounts of the hormone somatostatin. These tumors most commonly arise in the pancreas or duodenum and are a type of functional neuroendocrine tumor. The excess somatostatin produced disrupts the normal balance of gastrointestinal hormones, leading to a distinct cluster of symptoms.

Somatostatin normally acts as an inhibitory hormone, regulating the secretion of many other hormones such as insulin, glucagon, gastrin, and growth hormone. In somatostatinoma syndrome, the overproduction of somatostatin results in widespread metabolic and gastrointestinal disturbances. Early detection is crucial but often delayed due to the rarity of the syndrome and the non-specific nature of initial symptoms.

Causes

The primary cause of somatostatinoma syndrome is the presence of a somatostatin-secreting tumor, known as a somatostatinoma. These tumors are typically:

• Pancreatic in origin: Approximately 60% of cases arise in the pancreas.

• Duodenal or periampullary: Around 30% of tumors are located in the duodenum or near the ampulla of Vater.

• Other locations: Rarely, they may occur in the jejunum or elsewhere in the gastrointestinal tract.

Most somatostatinomas occur sporadically, but a small percentage may be associated with hereditary syndromes such as:

• Multiple Endocrine Neoplasia type 1 (MEN1)

• Von Hippel-Lindau disease

• Neurofibromatosis type 1

These tumors are usually slow-growing but may become malignant and metastasize, especially to the liver or lymph nodes.

Symptoms

The classic symptom triad of somatostatinoma syndrome includes:

• Diabetes or glucose intolerance: Due to suppression of insulin secretion by somatostatin.

• Steatorrhea (fatty stools): Caused by inhibition of pancreatic enzymes and bile flow.

• Cholelithiasis (gallstones): Resulting from reduced gallbladder contractility and bile secretion.

Other possible symptoms and signs include:

• Weight loss and malnutrition

• Abdominal pain or discomfort

• Nausea and vomiting

• Diarrhea or bloating

• Delayed gastric emptying

• Anemia, particularly if the tumor causes gastrointestinal bleeding

Because of its rarity and overlapping features with more common gastrointestinal disorders, the syndrome is often misdiagnosed or discovered incidentally during imaging or surgery for unrelated reasons.

Diagnosis

Diagnosis of somatostatinoma syndrome involves a combination of biochemical, imaging, and histological assessments:

Biochemical Testing

• Plasma somatostatin levels: Elevated levels confirm hypersecretion, although this test is not widely available.

• Chromogranin A: Often elevated in neuroendocrine tumors and used as a general tumor marker.

• Fasting blood glucose and insulin levels: To assess glucose intolerance or diabetes.

• Stool fat testing: To confirm steatorrhea.

Imaging Studies

• CT or MRI scans: Used to locate the primary tumor and detect metastases.

• Somatostatin receptor scintigraphy (OctreoScan): Highly sensitive for identifying somatostatin receptor-positive tumors.

• Endoscopic ultrasound (EUS): Useful for detecting small pancreatic or duodenal tumors.

Histopathological Examination

• Biopsy and immunohistochemical staining for somatostatin to confirm tumor type.

Treatment

Treatment of somatostatinoma syndrome focuses on tumor control, symptom management, and complication prevention. Therapeutic options include:

Surgical Resection

• Curative resection: Preferred treatment for localized tumors. Complete excision can alleviate symptoms and prevent progression.

• Palliative surgery: May be used to reduce tumor burden in metastatic cases.

Medical Therapy

• Somatostatin analogs (e.g., octreotide, lanreotide): Help suppress hormone secretion and control symptoms.

• Enzyme replacement therapy: For pancreatic insufficiency and steatorrhea management.

• Insulin or oral hypoglycemics: For diabetes management.

• Bile acid sequestrants: For managing bile salt diarrhea.

Other Therapies

• Targeted therapy: Such as everolimus or sunitinib in metastatic or progressive tumors.

• Peptide receptor radionuclide therapy (PRRT): For advanced tumors expressing somatostatin receptors.

Prognosis

The prognosis of somatostatinoma syndrome depends on several factors, including tumor size, location, presence of metastases, and response to treatment. Localized tumors that are surgically resected have a favorable outlook, and many patients achieve long-term remission.

However, prognosis worsens in metastatic disease, particularly when liver involvement is present. With appropriate management, symptoms can often be controlled, and quality of life maintained. Continued monitoring and follow-up are essential to detect recurrence and manage chronic complications such as diabetes and malabsorption.