Plasma Pancreatic Hormone Levels in a Case of Somatostatinoma: Diagnostic and Therapeutic Implications*

Abstract

Plasma somatostatin immunoreactivity (SIR) was elevated 40-fold in an insulin-treated diabetic with disseminated pancreatic carcinoma. The diagnosis of somatostatinoma was supported by histological and ultrastructural similarities between metastatic cells and pancreatic D cells. Under acid conditions, 75% of the plasma SIR eluted as a 6000- to 7000-dalton protein and 25% as synthetic somatostatin (mol wt 1600), whereas the 20-fold elevated urine SIR consisted almost exclusively of the higher molecular weight fraction. The hypersomatostatinemia was associated with reduced basal and stimulated pancreatic hormone levels, which might reflect its involvement in the steatorrhea and diabetes, and its protection against ketoacidosis. Plasma SIR rose 50% upon insulin withdrawal and 10-fold after tolbutamide injection and fell 30% after diazoxide. It is concluded that an increase in plasma and urine SIR, the presence of a 6000- to 7000-dalton SIR fraction in plasma and urine, a reduction in basal and stimulated pancreatic hormone levels, and tolbutamide-induced somatostatin release can be diagnostic for a somatostatinoma. Streptozotocin reduced tumor volume, hypersomatostatinemia, and tolbutamide-induced somatostatin release, suggesting that this drug may be useful in the treatment of disseminated somatostatinoma.

Clearance of Immunoreactive Somatostatin by Perfused Rat Liver

“…Similar precedents have been established for insulin, which is cleared and degraded more rapidly by the liver than proinsulin (29). Finally, it is conceivable that in certain diseases in man, such as somatostatinoma of the pancreas, the liver may restrict or limit increased amounts of free, biologically active, 1,600 mol wt somatostatin, secreted by these tumors (49) and identified in peripheral blood (49,50), from entering the systemic circulation unless the primary is large and/or hepatic metastases develop (49,50).…”

Diffuse somatostatin-immunoreactive D-cell hyperplasia in the stomach and duodenum

“…Pathological increases of somatostatin serum levels of between 40-fold and 100-fold greater than normal values are known from somatostatinomas (9000-1300 pg/ml). These were accompanied by very low basal serum growth hormone levels (0.8 ng/ml), without any response to stimulation in hypothalamic and pituitary functional tests (20,21).…”

“…Since 1979, pathological increased levels of circulating somatostatin have been described in sporadic cases of solid somatostatin tumors and in somatostatinomas containing subpopulations of other endocrine cells (19,20). Like gastrinomas, the tumors were mostly malignant and with few exceptions were predominantly located in the pancreas: two tumors in the duodenum (21,22) and one in the jejunum (23).…”

Somatostatinoma syndrome accompanied by overproduction of pancreatic polypeptide.

“…Plasma PP concentrations of the somatostatinoma syndrome were reported in 3 cases (Larsson et al 1977 ;Pipeleers et al 1979 ;Axelrod et al 1981). All cases showed low levels of plasma PP.…”