New insights on the pathogenesis of hypercalcemia in primary hyperparathyroidism

The pathogenesis of hypercalcemia in primary hyperparathyroidism is attribu ted to increased calcium release from bone, increased calcium reabsorption in renal distal tubules, and increased intestinal calcium absorption. Howev er, it remains unclear which factor is the main process. We encountered a 5 6-year-old woman with myasthenia gravis, in whom hypercalcemia and elevated serum parathyroid hormone (PTH) level were observed. Diagnosis of primary hyperparathyroidism was made. Treatment with methylprednisolone for myasthe nia gravis was associated with a marked decrease in both biochemical marker s of bone formation and resorption without any changes in endogenous cAMP a nd serum levels of calcium, PTH, and 1,25-dihydroxyvitamin D3 [1,25-(OH)(2) D-3]. These findings suggest that the possible pathogenesis of hypercalcemi a in primary hyperparathyroidism may be attributed to the increased calcium reabsorption in the kidney and the increased intestinal calcium absorption as a result of stimulated production of 1,25-(OH)(2)D-3 in the kidney. It thus follows that the renal tubular effect rather than the skeletal effect of the PTH excess may play a pivotal role in the development of hypercalcem ia in primary hyperparathyroidism.