Brown tumors of primary hyperparathyroidism may be a source of extrarenal 1,25-dihydroxyvitamin D production

Excerpt

Primary hyperparathyroidism (PHPT) is classically characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone (PTH) concentration. Associated biochemical indices include a serum phosphorus concentration in the lower range of normal [1], total alkaline phosphatase activity in the upper range of normal [2], low 25-hydroxyvitamin D (25(OH)D) levels [3], and 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels that are in the upper range of normal or frankly elevated [4]. PTH facilitates the 1α-hydroxylase enzymatic conversion of 25(OH)D to 1,25(OH)₂D, a property that helps to account for the classic depiction of 25(OH)D and 1,25(OH)₂D D levels in PHPT [5]. Other diseases associated with overproduction of 1,25(OH)₂D include sarcoidosis and tuberculosis in which macrophages in the associated granulomas have acquired the 1α-hydroxylase activity. In lymphomas as well, 1,25(OH)₂D-mediated hypercalcemia has been shown to be associated with abnormal synthesis of 1,25(OH)₂D by macrophages in the lymphomatous tissue [6]. Today, in parts of the world where calcium is measured routinely, most patients with PHPT lack the overt renal and skeletal manifestations of PHPT which include osteitis fibrosa cystica, a skeletal feature of PHPT characterized by marked radiographic demineralization, fibrosis, brown tumors, and cysts. Histologically, the brown tumors consist of giant cells and fibroblastic stroma. The presentation of such bone lesions is now considered to be an unusual manifestation of PHPT in countries where asymptomatic PHPT has become the predominant presentation of the disease. Thus, the elevated 1,25(OH)₂D level in the usual form of PHPT seen today is appropriately assumed to be of renal origin. However, in the case of PHPT associated with brown tumors, it is possible that the macrophages contained therein could contribute to excessive extrarenal production of 1,25(OH)₂D levels. …