Hyperparathyroidism, humoral hypercalcemia of malignancy, and the anabolic actions of parathyroid hormone and parathyroid hormone-related protein on the skeleton.

So what have we learned from the Takeuchi case? It has been 80 years since malignancy-associated hypercalcemia was described. It has been 45 years since HHM was first described. It has been 15 years since PTHrP was identified, and 12 years since PTHrP immunoassays became available for clinical research. We now know almost everything about HHM in pathophysiological terms, and we can reproduce the cardinal features of the syndrome in laboratory animals and humans. The Takeuchi case reminds us that we still have a few things to learn about HHM. Specifically, "Why is the regulation of 1,25(OH)2D different in patients with HHM and HPT?" and "Why is normal osteoblast-osteoclast coupling dysregulated in HHM?" or more fundamentally, "What regulates osteoblast-osteoclast coupling, and why is it deranged in HHM?" Given the rate of accumulation of new information about HHM, about the anabolic effects of PTH and PTHrP, and about osteoblast-osteoclast coupling over the past 10 years, there is reason to be optimistic that the answers to these questions will soon become clear.