Ectopic insulin and Occam's razor: reappraisal of the riddle of tumour hypoglycaemia.

The concept of ectopic insulin production is challenged on the basis of a review of 120 cases from the literature on extrapancreatic tumours associated with hypoglycaemia in which insulin or insulin-like activity were measured. No case met two or more of five criteria of ectopic hormone production. The evidence indicates that hypoglycaemia of extrapancreatic tumours cannot be attributed to insulin. In those rare cases in which plasma insulin was reported as high, pancreatic beta-cells could not be excluded as the source of insulin. Interestingly, many of these dubious cases had carcinoid histology. The review also points out a close association between some spindle-cell tumours and carcinoid tumours which may be relevant to discussion on the disputed origin of some "mesothelial" tumours. Nonsuppressible insulin-like activity (NSILA) consists of a number of factors mimicking insulin activity which compete with insulin or proinsulin for membrane receptors and may crossreact in bioassays, immunoassays, and receptor assays. The question of whether one or several of these substances may be responsible for extrapancreatic hypoglycaemia remains to be elucidated.