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Symptoms of an insulinoma following those of a glucagonoma
S184
ANALYSIS OF PANCREATIC POLYPEPTIDE (PP) IN ISLET CELL TUMOURS M.M.T. O'Hare, J.M. Sloan and K.D. Buchanan Depts. of Medicine and Pathology,
Queen's University,
Belfast, N. Ireland.
Islet cell tumours are associated with excess secretion of at least one of the gastrointestinal hormones giving rise to clinically defined syndromes. However, it is also recognised that when analysed for conent, many of these tumours are multi-hormonal. A heterogeneous group of clinically and histologically diagnosed islet cell tumours (n=16) have been assessed for PP content by radioimmunoassay. Tumours containing sufficiently high concentrations of PP were further investigated by determining the molecular species of PP present, using gel filtration. Acidified ethanol extracts of tumour tissue were gel filtered on Sephadex G-50 eluted with 0.05 M sodium acetate buffer pH 5.5, containing 0.2% (w/v) human albumin. Immunoreactive fractions of PP were detected using antisera (PP205 and PP221) with different regional specificities. PP205 was raised to bovine PP and PP221 to the C-terminal hexapeptide. Human PP standard and normal human pancreatic extracts eluted identically, demonstrating a single molecular species. Tumours containing grossly elevated levels of PP contained additional species of PP immunoreactivity, including large molecular weight (approximately IO,O00) species and small molecular weight peptides, containing the C-terminal amino sequence of PP. All other tumour tissue extracts contained a single species eluting identically to standard human PP. Hence, elevated levels of PP in addition to abnormal molecular species have been detected in some islet cell tumours suggesting that in some instances the peptide is directly involved in the pathology of these tumour syndromes possibly at cellular level.
SYMPTOMS OF AN INSULINOM~ FOLLO~,~NG THOSE OF A GLUCAGO~O~KA J. Schrezenmeir and ~. Kasper, Med. Univ.-Klinik ~drzburg, Deutschland
Bundesrepublik
This is a case report of a 58 year old female patient who underwent an exploratory laparotomy in 1978 because of a 1o kg weight loss (in two years), loss of appetite, recurrent vomiting, upper abdominal and shoulder pain, persistent constipation, anemia, glossitis and diabetes mellitus (managed by dietary therapy). During surgery, a tumor was located in the tail of the pancreas. In addition to liver cysts, there was diffuse liver metastasis. Histologically, this was shown to be apudoma tissue. During the end of 1979, a necrolytic erythema (with typical clinical and histological findings) appeared perineally and on the right great toe. This finding plus fasting pancreatic glucagon (K 964) levels of 6.7oo to 2o.ooo pg/ml confirmed the diagnosis of a malignant glucagonoma. The following characteristic symptoms were also present : Significant hypoaminoacidemia, a paradox rise in glucose following a tolbutamide provocation test, diabetic serial blood glucose levels, a pathological oGTT type I I I A (according to Kraft), anemia ana glossitis. By february 198o, all skin lesions had disappeared without recurrence in response to local and low dose corticosteroid therapy. In July, 1981, hypoglycemic shocks ~e~an occurrin~ without insulin suppression (42 mU/1 with a blood glucose of 21 m~!~ and 39 mU/1 with a blood glucose of 28 m~:. These characteristic symptoms of organic hyperinsulinism were not present in 1979 during repeated 2~ h fastin~ tests. A tolbutamide provocatio~ test performed at t ~ s time, revealed a paradox increase in 1~lood glucose (from 11o to I~5 m ~ afler 45 min~ an~ a concurrent increase in gluca~on (from !133 to 6266 p~/ml plasma). A transition from symptoms of gl~ca~onoma to symptoms of a~ insnlir~oma ha~ therefore occurred. We treated this patient with 5 ~ I ~ streptozotoci~ i.v. There were no further episodes of hypoglycemia an# the ~iabetes ~ow ree1~ire~ i~sulin therapy.
ANALYSIS OF PANCREATIC POLYPEPTIDE (PP) IN ISLET CELL TUMOURS M.M.T. O'Hare, J.M. Sloan and K.D. Buchanan Depts. of Medicine and Pathology,
Queen's University,
Belfast, N. Ireland.
Islet cell tumours are associated with excess secretion of at least one of the gastrointestinal hormones giving rise to clinically defined syndromes. However, it is also recognised that when analysed for conent, many of these tumours are multi-hormonal. A heterogeneous group of clinically and histologically diagnosed islet cell tumours (n=16) have been assessed for PP content by radioimmunoassay. Tumours containing sufficiently high concentrations of PP were further investigated by determining the molecular species of PP present, using gel filtration. Acidified ethanol extracts of tumour tissue were gel filtered on Sephadex G-50 eluted with 0.05 M sodium acetate buffer pH 5.5, containing 0.2% (w/v) human albumin. Immunoreactive fractions of PP were detected using antisera (PP205 and PP221) with different regional specificities. PP205 was raised to bovine PP and PP221 to the C-terminal hexapeptide. Human PP standard and normal human pancreatic extracts eluted identically, demonstrating a single molecular species. Tumours containing grossly elevated levels of PP contained additional species of PP immunoreactivity, including large molecular weight (approximately IO,O00) species and small molecular weight peptides, containing the C-terminal amino sequence of PP. All other tumour tissue extracts contained a single species eluting identically to standard human PP. Hence, elevated levels of PP in addition to abnormal molecular species have been detected in some islet cell tumours suggesting that in some instances the peptide is directly involved in the pathology of these tumour syndromes possibly at cellular level.
SYMPTOMS OF AN INSULINOM~ FOLLO~,~NG THOSE OF A GLUCAGO~O~KA J. Schrezenmeir and ~. Kasper, Med. Univ.-Klinik ~drzburg, Deutschland
Bundesrepublik
This is a case report of a 58 year old female patient who underwent an exploratory laparotomy in 1978 because of a 1o kg weight loss (in two years), loss of appetite, recurrent vomiting, upper abdominal and shoulder pain, persistent constipation, anemia, glossitis and diabetes mellitus (managed by dietary therapy). During surgery, a tumor was located in the tail of the pancreas. In addition to liver cysts, there was diffuse liver metastasis. Histologically, this was shown to be apudoma tissue. During the end of 1979, a necrolytic erythema (with typical clinical and histological findings) appeared perineally and on the right great toe. This finding plus fasting pancreatic glucagon (K 964) levels of 6.7oo to 2o.ooo pg/ml confirmed the diagnosis of a malignant glucagonoma. The following characteristic symptoms were also present : Significant hypoaminoacidemia, a paradox rise in glucose following a tolbutamide provocation test, diabetic serial blood glucose levels, a pathological oGTT type I I I A (according to Kraft), anemia ana glossitis. By february 198o, all skin lesions had disappeared without recurrence in response to local and low dose corticosteroid therapy. In July, 1981, hypoglycemic shocks ~e~an occurrin~ without insulin suppression (42 mU/1 with a blood glucose of 21 m~!~ and 39 mU/1 with a blood glucose of 28 m~:. These characteristic symptoms of organic hyperinsulinism were not present in 1979 during repeated 2~ h fastin~ tests. A tolbutamide provocatio~ test performed at t ~ s time, revealed a paradox increase in 1~lood glucose (from 11o to I~5 m ~ afler 45 min~ an~ a concurrent increase in gluca~on (from !133 to 6266 p~/ml plasma). A transition from symptoms of gl~ca~onoma to symptoms of a~ insnlir~oma ha~ therefore occurred. We treated this patient with 5 ~ I ~ streptozotoci~ i.v. There were no further episodes of hypoglycemia an# the ~iabetes ~ow ree1~ire~ i~sulin therapy.