The insulin-like growth factors and their binding proteins in a case of non-islet-cell tumour-associated hypoglycaemia

Abstract

Non-islet-cell tumours which induce hypoglycaemia are rare. Insulin-like growth factor-II (IGF-II) produced by some tumours is thought to be responsible for the hypoglycaemia and other systemic effects, despite normal or even low serum IGF-II levels. We studied a 44-year-old woman presenting with symptomatic hypoglycaemia associated with a large intraabdominal haemangiopericytoma. The serum IGF-II level was 455 micrograms/l when measured after acid-ethanol extraction (normal range (NR) 450-750 micrograms/l) and 1063 micrograms/l after acid chromatography (normal human serum pool 1068 micrograms/l). Levels of fasting plasma insulin, C-peptide, glucose and serum IGF-I levels were low before the operation (less than 2 mU/l (NR less than 2-14), 0.23 nmol/l (NR 0.4-1.2), 3.1 mmol/l, (NR 3.7-5.9) and 0.02 U/ml respectively). After tumour removal, the symptoms resolved rapidly and the patient made a full recovery. Secretion of both insulin and growth hormone was suppressed before the operation in response to a 75 g glucose meal and to an infusion of 100 micrograms GH-releasing hormone (GHRH) respectively in comparison with studies after the operation. Serum IGF-II levels 6 weeks and 12 weeks after the operation fell to 385 micrograms/l (777 micrograms/l; acid chromatography) and 280 micrograms/l (647 micrograms/l; acid chromatography) and serum IGF-I levels increased to 0.35 U/ml and 0.26 U/ml. Serum before the operation and tumour extract contained chiefly a large molecular weight precursor IGF-II (molecular weight 15,000-20,000) which disappeared from the serum after the operation. The IGF-binding proteins (IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4) were examined.(ABSTRACT TRUNCATED AT 250 WORDS)