The long-acting somatostatin analogue octreotide alleviates symptoms by reducing 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 and chromogranin A was treated with the somatostatin analogue octreotide for 2 years without any additional tumor-reducing interventions. Before therapy plasma glucagon was above 8 micrograms/l (normal < 0.2) and within 2 days 3 x 200 micrograms octreotide daily suppressed plasma glucagon to 2.2-2.5 micrograms/l. Concomitantly, chromogranin A dropped from 0.85 mg/l (normal < 0.1) to 0.2. After 3 weeks the preexisting disabling necrolytic migratory erythema had vanished completely, and weight loss was temporarily stopped. During therapy chromogranin A and plasma glucagon rose, exceeding pretreatment levels after 3 and 14 months, respectively. After 1 year the erythema recurred, responding only transiently to increasing doses of octreotide. The patient died after 2 years of therapy of tumor cachexy despite very high doses of octreotide (4 x 600 micrograms/day). Throughout treatment octreotide did not prevent tumor growth, as demonstrated by computed tomography and sonography. Determination of immunoreactive glucagon before and during octreotide therapy in fractions of 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 processing of preoproglucagon by octreotide, thereby reducing circulating bioactive glucagon. In summary, octreotide induced a remission of clinical symptoms by inhibiting posttranslational conversion of preproglucagon to glucagon but did not prevent tumor growth. Therefore, octreotide is a valuable therapy for rapid relief of clinical symptoms, thereby improving the possibilities for other tumor-reducing therapies.
Jockenhövel
F
F
Abteilung für Klinische Endokrinologie, Universität, Essen, Germany.
Lederbogen
S
S
Olbricht
T
T
Schmidt-Gayk
H
H
Krenning
E P
EP
Lamberts
S W
SW
Reinwein
D
D
D002455:Cell Division / Q000187:drug effects; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D005935:Glucagonoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D052336:Proglucagon; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012074:Remission Induction / Q000379:methods
D003692:Delayed-Action Preparations; D011498:Protein Precursors; D052336:Proglucagon; D005934:Glucagon; D015282:Octreotide