Humoral hypercalcemia of malignancy: Some enigmas on the clinical features

AbstractHumoral hypercalcemia of malignancy (HHM) is a common paraneoplastic syndrome mediated by tumor‐derived parathyroid hormone‐related peptide (PTHRP), which bears structural and functional similarities to PTH. Thus the clinical features of HHM are very similar to those of primary hyperparathyroidism (1° HPT), a prototype of humoral hypercalcemia caused by PTH. On the other hand, HHM syndrome differs from 1° HPT in several aspects, including serum 1,25(OH)2D levels, acid‐base balance, and bone remodeling process, the reason of which remains largely unknown. We approached these questions using a unique animal model of HHM, nude rats implanted with PTHRP‐overproducing human carcinomas. In this review we will summarize the results and discuss the implications in understanding the disease mechanism.