Search

The effect of intravenous somatostatin infusion was investigated in a patient with severe secretory diarrhea due to malignant carcinoid syndrome. Continuous somatostatin infusion for 48 hr (4 microgram/kg/hr) reduced stool volume from 2.2 to 0.7 liters/day. Intestinal perfusion studies before intravenous somatostatin infusion revealed decreased water and sodium absorption and jejunal chloride secretion. Somatostatin infusion for 2 hr (8 microgram/kg/hr) reversed chloride secretion to absorption and markedly enhanced water and sodium absorption. These results suggest that somatostatin inhibited a secretory component of water and ion movement in the small bowel of the patient with malignant carcinoid syndrome.

Diabetes mellitus, steatorrhea, cholelithiasis and a tumor distorting the duodenum prompted a work-up for somatostatinoma in a 52-year-old man. The responses of pancreatic B-cells but not of A-cells to nutrient stimuli were inhibited, and growth-hormone release was suppressed, suggesting somatostatin resistance in some target tissues. Plasma somatostatin-like immunoreactivity ranged from 9000 to 13,000 pg per milliliter (normal: 88+/-8, mean +/- S.E.M.) and was distributed in four molecular forms, including free somatostatin. The primary tumor contained 5 microgram of somatostatin-like immunoreactivity per milligram of wet tissue, distributed in three of the molecular forms noted in plasma. Plasma calcitonin was also elevated (4650 pg per milliliter; normal: less than 120). Immunocytochemical studies showed that cells of the primary tumor contained somatostatin and calcitonin but no other peptide hormones. Only somatostatin was present in the metastases. Somatostatin was localized electron microscopically in all secretory granules, irrespective of size and shape, whereas calcitonin was present only within a single subpopulation of small granules in the same cells.

Somatostatin has previously been shown to reduce nutrient absorption from the human jejunum. These studies were designed to examine whether changes in intestinal motility may be responsible for the inhibitory effect of somatostatin on intestinal absorption. Using triple-lumen perfusion techniques in healthy volunteers, somatostatin infusion (8 micrograms/kg/h) prolonged mean transit time from 9 to 16 min in a 30-cm jejunal test segment as estimated from dye dilution curves. Somatostatin infusion significantly reduced jejunal fructose absorption. Atropine (10 micrograms/kg/h, i.v.) caused a similar prolongation of mean transit time in the perfused jejunum. However, unlike somatostatin, atropine significantly increased fructose absorption. The observation that somatostatin and atropine affect absorption in opposite ways while prolonging intestinal transit time in a similar fashion suggests that the effects of somatostatin and atropine are due to a direct influence on absorption at the mucosal level that is independent of any effect on intestinal motility.

The present study was undertaken to investigate how a somatostatin analog (201-995 Sandoz), which is now commonly used for treatment of patients with gut hormone-producing tumors, affects water and ion absorption and transit time in the normal jejunum. Six healthy volunteers were given somatostatin analog intravenously at a dose of 1 microgram/kg/hr. At the same time, jejunal water and ion movement and transit time were measured using the triple-lumen tube technique [perfusion of a plasma-like electrolyte solution with PEG as a nonabsorbable marker at a rate of 15 ml/min; dye dilution curves ([3H]mannitol, [14C]PEG, BSP) for determination of jejunal transit time]. During somatostatin analog administration, transit time through a 30-cm segment of perfused jejunum increased from 4.0 min to 17.0 min. While the somatostatin analog increased jejunal transit time, it had no effect on net water and electrolyte absorption under steady-state conditions. The effect of somatostatin analog on the proximal small bowel is similar to the action of an eight-times higher dose of intravenous native somatostatin previously studied. The effect of the analog on transit time suggests a potentially beneficial effect in patients with large-volume diarrhea in which no tumor or circulating secretagogue can be identified, such as in pseudopancreatic cholera syndrome.

Somatostatin is found in both endocrine cells and nerve fibres of the gastrointestinal tract and has several inhibitory effects on the digestive tract. Somatostatin is a potent inhibitor of gastrin release; its secretion is regulated predominantly by the cholinergic pathway, which inhibits somatostatin and thus stimulates gastrin release. Gastric acid secretion is inhibited by both the paracrine and circulating peptide (hormonal) effects of somatostatin. Somatostatin secretion is a direct effect of acid on the somatostatin cell, since it is unaffected by the axonal blocker tetrodotoxin. Somatostatin antiserum eliminates the inhibitory effect of somatostatin and thus augments acid secretion. It therefore appears that somatostatin plays a physiological role in regulating gastric acid secretion, and it is possible that a lack of the inhibitory function of somatostatin is an aetiological factor in peptic ulcer disease. Postprandially, a rise in serum somatostatin concentration occurs which is twice as high with protein and fat as it is with carbohydrates. Several studies have shown that somatostatin inhibits nutrient absorption, indicating that somatostatin might be a physiological regulator in the homeostasis of ingested nutrients by modulating the intestinal absorption rate. Experiments have also demonstrated that somatostatin infusion inhibits intestinal motility; the interval between migrating myoelectric complexes is increased, and transit time is increased.

A 41-year-old woman with metastatic glucagonoma and the characteristic disabling rash, necrolytic migratory erythema, was treated with a synthetic somatostatin analog while waiting to undergo curative surgical resection. Plasma glucagon concentration (1,500-3,300 pg/ml, normal less than 200) remained elevated during analog therapy as the rash cleared. Only with surgical resection (partial pancreatectomy and partial hepatectomy) did glucagon levels return to normal. The therapeutic benefit caused by the analog in this syndrome differs from that in other endocrine tumor syndromes such as pancreatic cholera, carcinoid, or gastrinoma where circulating levels of tumor-produced agents are suppressed in conjunction with control of symptoms.

The effect of a synthetic somatostatin analog was studied in a patient with severe secretory diarrhea due to pancreatic cholera syndrome. Basal intestinal perfusion studies indicated an absence of water and sodium absorption, and active chloride secretion in the small bowel. Intravenous administration of the somatostatin analog (1 microgram/kg.h) changed zero net water movement to absorption (122 mL/30 cm of the jejunum per hour). Chloride secretion changed to absorption (5.0 to 7.9 meq/30 cm.h), and plasma vasoactive intestinal polypeptide concentration was reduced from 330 to 45 pmol/L (normal, less than 51). When the analog was given subcutaneously, 100 micrograms twice daily, stool weight decreased, and plasma vasoactive intestinal polypeptide concentration fell toward the normal range (67 pmol/L). Plasma concentration of pancreatic polypeptide was initially elevated and dropped during intravenous infusion of somatostatin analog but returned to baseline on maintenance therapy with the analog delivered subcutaneously. The patient has not had further diarrhea during 9 months of therapy.

This study was designed to elucidate the mechanism by which somatostatin administration ameliorates or abolishes diarrhea in pancreatic cholera syndrome (PCS). Absorption (or secretion) of water and electrolytes was measured in 30-cm segments of jejunum of 18 healthy volunteers in whom PCS was mimicked by intravenous infusion of VIP. Using the triple-lumen tube technique, the intestine was perfused with a plasma-like electrolyte solution while administering intravenous saline (control), VIP (400 pmol/kg/hr), somatostatin (5000 pmol/kg/hr), or VIP plus somatostatin. VIP infusion abolished water and electrolyte absorption and somatostatin had no effect on these VIP-induced transport changes regardless of whether somatostatin infusion was started before or after VIP infusion. Somatostatin infusion had no effect on VIP plasma concentration when elevated by intravenous VIP infusion (control: 10 +/- 1 pmol/l; during VIP infusion: 108 +/- 6). In a patient with pancreatic cholera syndrome identical perfusion experiments showed jejunal water secretion (93 ml/30 cm/hr) which changed to absorption (65 ml/30 cm/hr) when somatostatin was infused (5000 pmol/kg/hr). Plasma VIP concentration fell from 145 to 74 pmol/l (normal less than 50) during somatostatin infusion. Stool weight fell from 3722 g to 819 g per 24 hours when somatostatin was given at a dose of 2500 pmol/kg/hr for two days. Our observations in healthy subjects show that somatostatin has no effect on intestinal transport at the mucosal level when circulating VIP concentration is elevated.(ABSTRACT TRUNCATED AT 250 WORDS)