Secretion of hypothalamic and pituitary hormones by non-endocrine tumours.

That non-endocrine cancers can produce clinical syndromes of apparent hormone excess has been known for some time (Rees and Ratcliffe, 1974). Now there is ample clinical and biocheinical evidence that many polypeptide hormones may be produced and released by human tumours which originate in tissues which are not normally regarded as sites for the physiological production of the hormones. In some instances-for example, inappropriate production by a cancer of adrenocorticotrophic hormone-that syndrome may be clinically obvious. Thus Cushing's syndrome in a patient witha relatively slowly growing lung cancer or carcinoid will be obvious. More commonly with ectopic ACTH production, however, the full clinical picture of Cushing's syndrome is not apparent-rather there is pronounced muscle weakness, hypokalaemic alkalosis, pigmentation, and very high levels of plasma cortisol and ACTH. Most of the ectopic humoral syndromes are diagnosed on the clinical and biochemical improvement after tumour resection, on finding high plasma and tumour extract concentrations of hormones, in some patients on localisation of hormones in tumour cells by immunofluorescence, and on the presence of an arteriovenous gradient of hormone concentration across the tumour. There are now many instances of cultured cancer cells being shown to release hormone into the culture medium. In a few cases the biosynthesis of hormone has been demonstrated by the incorporation of radioactive amino-acids into the peptide. Although most research in this area has been concentrated on the study of hormone production, presumably because hormones readily manifest their presence, other polypeptides also are produced and released by tumours in greater quantities than would be expected from the tissue of origin. These include enzymes such as alkaline phosphatase (Nathanson and Fishman, 1971), lysozyme (Kovanyi and Letnansky, 1971), amylase (Amman et al., 1972), and plasminogen activator (Davidson et al., 1969) as well as a variety of fetal proteins that are normally present in plasma only in small quantities during adult life (Alexander, 1972), such as carcinoembryonic antigen (Gold, 1970) and alpha fetoprotein (Abelev, 1971).