Somatostatinoma is a tumor originating from pancreatic D cells. Due to the tumor releasing large amounts of somatostatin (SS), it causes a combination of diseases such as steatorrhea, diabetes, hypochlorhydria, and cholelithiasis, also known as somatostatinoma syndrome. Somatostatin is a polypeptide composed of 14 amino acids, first isolated from the hypothalamus of rats in 1968. It was found to inhibit the release of growth hormone and was named somatotropin release-inhibiting factor (SRIF). It has now been discovered that somatostatin is present in the hypothalamus, pancreatic D cells, stomach, duodenum, and small intestine, and can broadly inhibit the release of various peptide substances. Therefore, this hormone not only inhibits endocrine and exocrine secretions but also suppresses intestinal peristalsis and gallbladder contraction, earning it the name "inhibitory hormone." In 1977, Ganda and Larsson independently described somatostatinoma in their reports. In 1979, Krejs comprehensively outlined the clinical features of this disease. Somatostatinoma is one of the rarest functional endocrine tumors, with fewer than 50 cases reported internationally to date, and no documented cases in domestic literature. The age of onset for this disease is relatively advanced, ranging from 26 to 84 years, with an average age of 51. The incidence is nearly equal between male and female patients.

bubble_chart Pathological Changes

Somatostatinomas generally have larger tumor masses, ranging from 1.5 to 10 cm, with an average of 5 cm. About 90% of the tumors are solitary and single. Approximately 68% of somatostatinomas originate from the pancreas, with 75% located in the pancreatic head, 20% in the body and tail, and the remaining 5% widely distributed throughout the pancreatic parenchyma. A significant number of somatostatinomas arise from extra-pancreatic organs, including the duodenum (19%), the ampulla of Vater (3%), and the small intestine (3%). Most somatostatinomas are malignant, with three-quarters of patients already having metastases at the time of diagnosis. Common metastatic sites include the liver, peripancreatic lymph nodes, and bone marrow.

Under light microscopy with conventional staining, it is difficult to distinguish cell types and characteristics, making definitive diagnosis impossible. Electron microscopy reveals well-differentiated islet cells containing D-cell granules. Immunofluorescence techniques show a positive reaction to somatostatin. The latter two methods serve as the primary pathological basis for diagnosing this disease.

2. Pathophysiological Changes

Since somatostatin inhibits the release of polypeptide hormones, it can cause widespread pathophysiological changes in the body, mainly including the following aspects:

(1) Central Nervous System: Inhibits the pituitary gland from releasing tropic hormones such as growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, and prolactin.

(2) Gastrointestinal Tract: Somatostatin directly inhibits gastric acid secretion, gastric emptying, duodenal motility, biliary and gallbladder motility, pancreatic exocrine function, and the absorption of glucose, amino acids, and triglycerides. It exerts a paracrine effect locally in the gastrointestinal tract, providing negative feedback regulation for digestion and metabolic processes finely controlled by peptides.

(3) Endocrine System: Somatostatin significantly inhibits the release of endocrine hormones in the gastrointestinal system, particularly the pancreas. These hormones include insulin, glucagon, gastrin, motilin, secretin, cholecystokinin, pancreatic polypeptide, and vasoactive intestinal peptide (VIP). Whether in normal or tumor tissues, somatostatin inhibits the release of these peptide hormones through specific or receptor-mediated actions.

The common clinical manifestations and their incidence rates of somatostatinoma are shown in Table 1.

Table 1 Clinical Manifestations of Somatostatinoma ^*

*Harris G, Tio F, Cruz A. J Surg Oncol, 1987, 36:8

1. Diabetes

Most patients with this condition develop diabetes or impaired glucose tolerance, ranging from mild hyperglycemia to significant ketoacidosis. The cause of diabetes is the secretion of large amounts of somatostatin by the tumor, which inhibits insulin release. In some patients, the tumor tissue replaces the pancreas, severely limiting insulin synthesis.

However, about 10% of patients experience hypoglycemia, the mechanism of which remains unclear. It is speculated that the tumor may inhibit normal self-regulatory mechanisms such as glucagon and growth hormone or impair glucose absorption.

2. Hypochlorhydria

Since somatostatin inhibits gastrin secretion and gastric acid production, all patients develop hypochlorhydria, with some even experiencing achlorhydria. Patients exhibit symptoms of dyspepsia and postprandial epigastric fullness.

3. Cholelithiasis

26–65% of patients develop cholelithiasis, with about 16% accompanied by skin and scleral jaundice. The causes of gallstones may include: ① Somatostatin inhibits the release of cholecystokinin (CCK). ② It suppresses the motility of the biliary tract and gallbladder. ③ Lipid metabolism disorders.

AD

TCM can effectively treat dry eye syndrome, floaters, retinopathy, and various chronic eye diseases

The incidence of abdominal pain is approximately 35%, and its mechanisms include: ① Impaired nutrient absorption. ② Delayed gastrointestinal motility. ③ Tumor compression or secondary infection.

5. Diarrhea

In this disease, 26% of patients exhibit diarrhea, which is caused by the increased osmotic pressure in feces due to malabsorption of sugars, fats, and amino acids. Some patients experience steatorrhea. Approximately 19% of individuals with somatostatinoma develop steatorrhea, as the decline in the exocrine function of the pancreas leads to impaired digestion and absorption of fats, thereby contributing to the condition.

In summary, the clinical manifestations of somatostatinoma are highly complex and diverse, and these symptoms are also very common in many other diseases. Some refer to the simultaneous occurrence of diabetes, cholelithiasis, and steatorrhea as the "triad" of somatostatinoma.

bubble_chart Auxiliary Examination

1. Laboratory Tests

(1) Gastric juice analysis: Hypochlorhydria or even achlorhydria.

(2) Elevated blood glucose or decreased glucose tolerance test results.

(3) Basal plasma somatostatin measurement: This is the primary basis for diagnosing this condition. Any patient suspected of having a somatostatinoma should undergo plasma somatostatin level testing. Under fasting conditions in the morning, normal somatostatin levels are <100 pg/ml, while in somatostatinoma patients, levels range from 0.16 to 107 ng/ml, averaging 15.5 ng/ml. However, a small number of patients may yield false-negative results.

(4) Provocative tests: For patients clinically suspected of having a somatostatinoma but with no elevation in plasma somatostatin levels, provocative tests can further clarify the diagnosis. ① Tolbutamide (D860) provocative test: Intravenous injection of tolbutamide can stimulate the release of somatostatin in patients with tumors, leading to a significant increase in plasma somatostatin levels, whereas no such increase occurs in individuals without tumors. ② Calcium-Pentagastrin Test: In patients with this condition, plasma somatostatin levels can double within 3 minutes after intravenous injection of calcium (calcium gluconate) and pentagastrin, gradually returning to normal after 10 minutes. Both pancreatic and extrapancreatic somatostatinoma patients with liver metastases also exhibit significantly elevated plasma somatostatin levels. This test does not increase somatostatin concentrations in normal individuals or patients with pancreatic adenocarcinoma.

2. Localization Diagnosis

(1) Gastrointestinal barium meal or duodenal hypotonic contrast examination: For tumors located in the descending duodenum or pancreatic head, filling defects, enlarged duodenal loops, or indentations may be observed, but these methods are not helpful for tumors in the pancreatic body or tail.

(2) B-ultrasound, CT, or MRI: Since the tumors in this condition are typically large, primary pancreatic tumors and liver metastases can often be detected, yielding a high localization diagnostic rate.

(3) Selective abdominal angiography: This can reveal hypervascular pancreatic tumors and their liver metastases, with diagnostic significance comparable to B-ultrasound, CT, and MRI, and a diagnostic rate exceeding 85%. However, these examinations can only confirm the presence of a tumor and cannot provide a qualitative diagnosis.

bubble_chart Diagnosis

Due to the complex and diverse clinical manifestations of this disease, diagnosis is extremely difficult, especially early diagnosis. If a patient presents with the triad of diabetes, cholelithiasis, and steatorrhea, along with symptoms such as dyspepsia, hypochlorhydria, weight loss, abdominal pain, or an abdominal mass, the possibility of a somatostatinoma should be considered. Further localization of the tumor can be achieved through laboratory tests, gastrointestinal barium meal, duodenal hypotonic contrast examination, B-ultrasound, CT, MRI, and selective abdominal angiography.

bubble_chart Treatment Measures

1. Surgical Treatment

Surgical intervention is the primary method for treating somatostatinomas. However, due to the high metastasis rate in patients with this condition, the surgical resection rate is not very high. Additionally, since most patients have large tumors, tumor enucleation is often unsuitable; therefore, pancreatic resection is the main surgical approach.

(1) For tumors located in the body or tail of the pancreas, a distal pancreatectomy can be performed.

(2) For tumors in the head of the pancreas, subtotal pancreatectomy or pancreaticoduodenectomy (Whipple procedure) is recommended.

(3) For large tumors that cannot be radically resected or for liver metastases, palliative debulking surgery can often alleviate symptoms and prolong survival.

2. Medical Treatment

For patients with advanced-stage tumors who are not candidates for surgery, comprehensive medical treatment measures can be adopted. However, due to the limited number of cases, the evaluation of specific chemotherapy regimens and their efficacy is somewhat constrained. In one group of 4 patients treated solely with medical therapy, 1 patient treated with Streptozotocin alone achieved partial symptom relief and survived for 5 years. In another group of 3 patients, 2 treated with Streptozotocin plus 5-FU showed significant symptom improvement, while the remaining patient treated with Doxorubicin alone also experienced partial symptom relief. Combining the outcomes of these two groups, the 1-year survival rate was 48%, and the 5-year survival rate was 13%.

bubble_chart Complications

Diabetes, cholelithiasis, and other conditions.