AJP - Endocrinology and Metabolism, Vol 252, Issue 6 E790-E798, Copyright © 1987 by American Physiological Society
Animal model of primary hyperparathyroidism
P. Jaeger, W. Jones, M. Kashgarian, R. Baron, T. L. Clemens, G. V. Segre and J. P. Hayslett
An experimental model of hyperparathyroidism was developed in the rat to
simulate primary hyperparathyroidism in humans. In this model
thyroparathyroidectomized (TPTX) or parathyroidectomized (PTX) animals were
infused for 6 days with an amount of bovine synthetic parathyroid hormone
(PTH)-(1-34) fragment to restore plasma calcium levels to normal (0.7 U X
h-1) or with PTH at twofold (1.4 U X h-1) or threefold (2.1 U X h-1) this
basal level. Animals infused with 2.1 U X h-1 of bovine PTH-(1-34)
exhibited hypercalcemia, hypophosphatemia, a reduction in theoretical renal
threshold for phosphate and an increase in 1,25-dihydroxyvitamin D plasma
levels that were approximately threefold the control value. In addition,
these animals demonstrated nephrocalcinosis and changes of bone histology
that were typical of the findings in patients with primary
hyperparathyroidism. In contrast, in animals infused at 1.4 U X h-1, plasma
calcium, phosphate, and theoretical renal threshold for phosphate remained
within normal limits, but plasma 1,25-dihydroxyvitamin D was increased
above control, suggesting that increased activity of 1 alpha-hydroxylase
may be the most sensitive index of increased PTH levels. This animal model
permits sustained elevation of PTH plasma levels at basal or pathologically
elevated levels and should provide an effective means by which to evaluate
the consequences of chronic hyperparathyroidism on epithelial function,
bone, and other organ systems.
