DISCOVERY OF PTHrP Hypercalcaemia has been recognised as a metabolic complication of malignancy since 1924 [1]. In 1941 Albright proposed that hypercalcaemia in a patient with renal carcinoma, which resolved after irradiation of a single bone metastasis, might be due to production by the cancer of parathyroid hormone (PTH)[2]. In succeeding years this idea gained acceptance and the term,ectopic PTH syndrome', was widely used to apply to patients with cancer who had a high plasma calcium level, low phosphorus and minimal or no bony metastases [3]. Support for this came in 1966 when Berson and Yalow [4] published results with the first radioimmunoassay (RIA) for PTH, in which they found significant elevations of the PTH level in a number of unselected patients with lung cancer. Over the next several years until the early 1970s, several reports were published of measurable PTH (by radioimmunoassay) in extracts of cancer from such patients [5].

Throughout this time it was evident, however, that the RIA of PTH presented technical problems and in none of the above instances were circulating levels of PTH convincingly very highÐcertainly not at the levels frequently found with corresponding degrees of elevation of plasma calcium in patients with primary hyperparathyroidism. In the early 1970s some doubt arose regarding the nature of the hor-