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A case of hepatoma associated with hypoglycaemia and overproduction of IGF‐II (E‐21): beneficial effects of treatment with growth hormone and intrahepatic adriamycin
Author(s) -
Hunter Steven J.,
Daughaday William H.,
Callender Michael E.,
McKnight John A.,
Mcllrath Edwin M.,
Teale J. Derrick,
Atkinson A. Brew
Publication year - 1994
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1994.tb02564.x
Subject(s) - medicine , endocrinology , somatostatin , somatomedin , growth factor , insulin , proinsulin , insulin like growth factor 2 , basal (medicine) , insulin like growth factor , chemistry , insulin like growth factor binding protein , biology , receptor
Summary We describe a case of recurrent hypoglycaemia associated with a hepatoma. During hypoglycaemia serum insulin was undetectable. Plasma Insulin‐like growth factor II (IGF‐11) 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‐l 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/1 (mean ± SEM) before treatment, compared with 4·86mmol/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 GH treatment was successfully withdrawn with no effect on plasma glucose or growth factor levels.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. Twenty‐four months after his initial presentation he developed malignant ascites. Despite this evidence of tumour progression there was no recurrence of hypoglycaemia, and E‐21 and insulin‐like growth factor concentrations were normal. There was an initial response to intravenous chemotherapy with mithozantrone but subsequently he deteriorated and died 26 months after presentation. We conclude that E‐21 was useful in the diagnosis of this case of non‐islet cell tumour hypoglycaemia. GH was a helpful initlal treatment to prevent hypoglycaemia. However, the most beneficial therapy was Intrahepatic adriamycin which had a marked effect on plasma levels of E‐21. Hypoglycaemia was eliminated. It is possible that the decrease In circulating growth factors also had a beneficial effect on tumour growth, the patient having had a prolonged remission and excellent quality of life before the eventual development of malignant ascites.