Humoral hypercalcemia of malignancy

At the Annual Meeting of the American Society for Bone and Mineral Research last June, three groups announced the isolation and amino-acid sequencing of a protein that appears to be responsible for humoral hypercalcemia of malignancy (HHM) (1-4). Isolation of the protein, the cloning of the cDNA that encodes it and the resultant elucidation of the full-length amino-acid sequence of the HHM-factor (5, 6) cap years of steady progress in this field and have implications that extend beyond the syndrome of humoral hypercalcemia of malignancy. It is timely to review the clinical syndrome as well as its history and pathophysiology, to examine the structure of the HHM-factor as it relates to the observed clinical and biochemical manifestations of the condition, to consider current and future directions of research involving this novel 'hormone', and to delineate the clinical impact of this recent discovery.