Malignant Somatostatinoma: Clinical Features and Metabolic Studies*

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Abstract
We describe the results of metabolic studies in a woman who exhibited the characteristic clinical and pathological features of a malignant somatostatinoma and who had, in addition, several novel manifestations of this syndrome: metastases to many organs other than the liver (including skin and bone), the presence of an immunoglobulin G K-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 and 5-fluorouracil and then fell toward the previous level. These changes were associated with variations in the hormonal responses to oral glucose and to iv 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 responses tc 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 FFA, 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. Thus, ketosis developed in this patient with a somatostatinoma at a rate comparable to that seen in insulin-dependent diabetes mellitus. We conclude that there is a graded relationship between the plasma SLI level and the biological effects of endogenous somatostatin produced by an islet cell tumor; that the relationship in man between the plasma SLI level and its biologicaleffect, such as inhibition of arginine-induced hormone secretion, is different for different hormones; that mild fasting hyperglycemia can occur during inhibitionof IRI and IRG secretion by endogenoussomatostatin, consistent with the view that hyperglucagonemia is not a necessary condition for the occurrence of mildfasting hyperglycemia; and that significant ketosis can be a clinical feature of the somatostatinoma syndrome.