MALIGNANT SOMATOSTATINOMA - CLINICAL-FEATURES AND METABOLIC STUDIES

The results of metabolic studies in a woman who exhibited the characteristic clinical and pathological features of a malignant somatostatinoma are described. She also had several novel manifestations of this syndrome; metastases to many organs other than the liver (including skin and bone), the presence of an Ig G .kappa.-type M-component, and marked hyperglycemia and ketonuria, necessitating insulin therapy. The M-component and the metastases to bone led to the erroneous diagnosis of multiple myeloma. The plasma level of somatostatin-like immunoreactivity (SLI) rose after therapy with streptozotocin 5-fluorouracil and then fell toward the previous level. These changes were associated with variations in the hormonal responses to oral glucose and to i.v. arginine and with variations in hormone secretion and fuel flow during insulin withdrawal. When the SLI level rose, the immunoreactive insulin (IRI) response to oral glucose was reduced. Progressively higher basal SLI levels were associated with progressive inhibition of the IRI response to arginine. The immunoreactive glucagon (IRG) and GH growth hormone responses to arginine were fully inhibited by plasma SLI levels that did not fully inhibit the IRI response, indicating differential sensitivity to somatostatin. During insulin withdrawal on 2 occasions, the patient developed mild hyperglycemia (130-157 mg/dl) despite suppression of the plasma IRG level, consistent with the effects of exogenous somatostatin in normal subjects. After therapy, when the plasma SLI level was higher (and the IRI level lower) than before, plasma free fatty acid, blood glycerol, and total blood ketone values reached higher levels than in the study before therapy. The peak total blood ketone level was 5.02 mM after therapy, 3.14 mM before therapy. Ketosis developed in this patient with a somatostatinoma at a rate comparable to that seen in insulin-dependent diabetes mellitus. There is a graded relationship between the plasma SLI level and the biological effects of endogenous somatostatin produced by an islet cell tumor; the relationship in man between the plasma SLI level and its biological effect, such as inhibition of arginine-induced hormone mild fasting hyperglycemia can occur during inhibition of IRI and IRG secretion by endogenous somatostatin, consistent with the view that hyperglucagonemia is not a necessary condition for the occurrence of mild fasting hyperglycemia; and that significant ketosis can be a clinical feature of the somatostatinoma syndrome.