Carcinoid tumors are the most frequent gut neuroendocrine tumors accounting for more than 50% of all tumors of the gastroenteropancreatic (GEP) axis. These tumors appear to derive from a stem cell line capable of differentiating into a variety of malignant cells that secrete many different peptides and amines. The symptoms of carcinoid tumors are often non-specific, vague abdominal pain that may precede the diagnosis by a median of 9 years. Carcinoid syndrome occurs in less than 10% of patients. We evaluated the effects of SMS 201-995 in 14 such patients, 12 with diarrhea, 8 with flushing, 3 with wheezing, one with tricuspid valve incompetence, 6 with facial telangiectasia, 3 with a pellagra type dermatosis and one with myopathy. Diarrhea was abolished or significantly reduced in 83%, flushing in 100%, wheezing in 100%, and myopathy improved in the one patient. Blood serotonin was resistant to change, urine 5HIAA fell in 75%, and most gut neuropeptide hormones apart from somatostatin were suppressed. Tumor growth appeared to be slowed in 2/3 of cases treated for up to 4 years. The analog of somatostatin appears to be a useful addition to the therapeutic armamentarium for carcinoid tumors and the symptom complex.

A review is given on the clinical features of carcinoid syndrome including symptomatology, diagnostics, biochemistry and treatment. We have reviewed the literature on current therapy of carcinoid patients with special emphasis on the use of the somatostatin analogue SMS 20-1995. In addition, we present data on the effects of SMS 201-995 on indices of a clinical, biochemical and tumor growth. Diarrhea is abolished or significantly reduced in 75% of patients, flushing improves in 100%, wheezing in 100% with a decrease in airways resistance, and in one patient myopathy has improved. Blood serotonin is notoriously resistant to intervention and urinary 5-HIAA will decrease in 75% of causes but subsequently rebounds in 38%. Tumors, in general, continue to grow, but this may be slowed or in rare cases tumor growth is arrested. In individual instances the tumor may even infarct, leading to spontaneous cure. Tumors secreting PP, ACTH and calcitonin may be particularly resistant to treatment, whereas VIP secreting tumors appear to be sensitive.

SMS 201-995 (Sandostatin) was studied using low doses (50 to 100 micrograms) administered subcutaneously every 12 hours. A single 50-micrograms dose of SMS 201-995 effectively controlled gastric acid and blood gastrin levels for 12 hours in three patients with benign gastrinomas and was useful in their perioperative management. Higher doses of the agent (500 to 800 micrograms per day) had no effect on metastases in one of two patients with metastatic gastrinoma. In the other patient, one tumor shrank but the other continued to grow after three months of treatment while serum gastrin levels did not change. Cultured metastatic tumor tissue from this patient released different forms of gastrin; growth rates varied, independent of uptake of SMS 201-995, and gastrin release increased. A neonate with nesidioblastosis maintained normal blood glucose levels while receiving SMS 201-995 therapy following a 95 percent pancreatic resection. In two elderly patients with organic hypoglycemia--one with a single benign adenoma and one with multiple adenomatosis--the somatostatin analogue did not prolong the hypoglycemia-free interval. In nine patients with carcinoid syndrome, flushing was uniformly controlled with 50 micrograms of SMS 201-995 administered every eight to 12 hours. One of the nine required exocrine pancreatic replacement. After six months of treatment, three of the nine had no change in tumor size and one had remission of symptoms and stopped treatment. In two patients with vipoma, SMS 201-995 controlled diarrhea and reduced levels of vasoactive intestinal peptide; tumor necrosis occurred in one patient. In a patient with diabetic diarrhea unresponsive to all treatments, SMS 201-995 therapy controlled the diarrhea but did not interfere with control of the diabetes.

We have determined the effects of Sandostatin (SMS 201-995, Sandoz) on chromogranin-A (CgA) in the blood of 14 patients with neuroendocrine tumors of the gastroenteropancreatic axis, 7 with carcinoid tumors, 5 with gastrinomas, and 1 each with a glucagonoma and tumor-secreting vasoactive intestinal peptide. Two thirds of the patients had elevated plasma CgA. Sandostatin administration suppressed CgA in 12 of the 14 patients. In 8 of 10, the clinical response to Sandostatin paralleled the reduction in CgA levels. There was a strong correlation between the change in CgA levels and the respective blood concentration of the hormone produced by the tumor. Serial measurement of CgA may provide an additional means of monitoring these tumors and their secretory activity where other measures are not available.

Osteitis fibrosa cystica (brown tumors) can be a skeletal manifestation of advanced hyperparathyroidism, including parathyroid cancer. Severe osteitis fibrosa cystica can mimic metastatic bone diseases especially in patients with a history of cancer. Because the treatment and prognosis of these two problems differ greatly considering hyperparathyroidism in the differential diagnosis of patients found to have osteolytic lesions is critical for the appropriate management of these patients. In this case report we describe a patient with a history of renal cell cancer and presumed osteolytic bone metastases. During prophylactic intramedullary rodding to prevent pathologic fracture of her femur she was found to have a benign lesion related to her previously undiagnosed hyperparathyroidism caused by an underlying parathyroid cancer. A detailed review of this disease and the associated bone changes is also included to underscore the importance of an adequate differential diagnosis as well as optimal management. Patients with hypercalcemia or bony lesions should not automatically be treated palliatively for metastatic disease just because of a past medical history of cancer. Hyperparathyroidism is a readily curable problem if properly diagnosed.