A case of hepatoma associated with hypoglycaemia and overproduction of IGF-II (E-21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin.
We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma insulin-like growth factor II (IGF-II) was not elevated although 71% of plasma IGF-II was present as big IGF-II (molecular weight 11 kDa) which probably represents a non-glycated form of pro-IGF-II. The GH response to hypoglycaemia was impaired and plasma levels of both IGF-I and the GH-dependent IGF binding protein (IGFBP-3) were low. A recently described unextracted assay directed against the first 21 amino acids of the E-domain (E-21) of proinsulin-like growth factor-II (pro-IGF-II) allows direct plasma estimation (plasma E-21) of larger molecular forms of IGF-II without interference from normal IGF-II and IGF binding proteins. Basal values were grossly elevated (23.7 and 23.8 nmol/l). Treatment with GH led to an increase in the mean plasma glucose across 24 hours (4.25 +/- 0.21 mol/l (mean +/- SEM) before treatment, compared with 4.86 mmol/l +/- 0.17 following GH (P < 0.01)) and a reduction in hypoglycaemic attacks. The treatment was associated with a rise in IGFBP-3 and small increases in insulin like growth factors. Subsequent treatment with the somatostatin analogue octreotide did not produce a significant change in plasma glucose levels or insulin-like growth factors. Two courses of intrahepatic adriamycin restored elevated levels of E-21 to normal. Total IGF-II remained normal and IGF-I increased. GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels. The patient remained free from hypoglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Hunter
S J
SJ
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, Northern Ireland, UK.
Daughaday
W H
WH
Callender
M E
ME
McKnight
J A
JA
McIlrath
E M
EM
Teale
J D
JD
Atkinson
A B
AB
D000287:Administration, Topical; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D002352:Carrier Proteins / Q000032:analysis; D004317:Doxorubicin / Q000008:administration & dosage*; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000209:etiology*; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008113:Liver Neoplasms / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D013002:Somatomedins / Q000032:analysis
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004317:Doxorubicin; D013006:Growth Hormone