Parathyroid gland volume increases with postmaturational aging in the rat

To examine the pathophysiology of the age-related rise in the plasma concentration of parathyroid hormone (PTH), we studied the relationships among plasma immunoreactive PTH (iPTH), parathyroid gland volume, parathyroid cell proliferation rate, renal function, and blood Ca(2+) in male Fischer 344 rats aged 6-28 mo. Plasma iPTH increased 2.5-fold between 6 and 28 mo and correlated with parathyroid gland volume (r = 0.87). Gland volume began to increase as early as 6-12 mo of age and by 28 mo was threefold greater than at 6 mo. Gland expansion was a consequence of hyperplasia stimulated in part by an increase in cell proliferative activity late in life. Blood Ca(2+) and plasma inorganic phosphorus did not change significantly with age. Glomerular filtration rate decreased with age but only after the age of 24 mo. Unlike what has been observed in the human, these data suggest that the age-related increase in plasma iPTH in the rat is linked to parathyroid gland hyperplasia and that early gland growth does not appear to be associated with hypocalcemia or renal insufficiency, but rather to developmentally related metabolic changes. Later in life (>24 mo), the increase in parathyroid cell proliferation rate, further hyperplastic expansion of the gland, and increase in iPTH secretion appear to be associated with renal insufficiency.