THE LONG-ACTING SOMATOSTATIN ANALOG OCTREOTIDE ALLEVIATES SYMPTOMS BYREDUCING POSTTRANSLATIONAL CONVERSION OF PREPRO-GLUCAGON TO GLUCAGON IN A PATIENT WITH MALIGNANT GLUCAGONOMA, BUT DOES NOT PREVENT TUMOR-GROWTH

A 52-year-old female with metastatic glucagonoma secreting glucagon an d chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Befo re therapy plasma glucagon was above 8 mu g/l (normal <0.2) and within 2 days 3x200 mu g octreotide daily suppressed plasma glucagon to 2.2- 2.5 mu g/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (norm al <0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic mi gratory erythema had vanished completely, and weight loss was temporar ily stopped. During therapy chromogranin A. and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. Aft er 1 year the erythema recurred, responding only transiently to increa sing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4x600 mu g/day). Throughout treatment octreotide did not prevent tumor growth, as demo nstrated by computed tomography and sonography. Determination of immun oreactive glucagon before and during octreotide therapy in fractions o f plasma samples subjected to gel chromatography revealed a reduction in the ratio of glucagon to preproglucagon from 1.83 (before) to 0.56 (during therapy), indicating inhibition of posttranslational processin g of preproglucagon by octreotide, thereby reducing circulating bioact ive glucagon. In summary, octreotide induced a remission of clinical s ymptoms by inhibiting posttranslational conversion of preproglucagon t o glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby impr oving the possibilities for other tumor-reducing therapies.