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Lack of involution of hyperplastic parathyroid glands in dogs: Adaptation via a decrease in the calcium stimulation set point and a change in secretion profile
Author(s) -
Cloutier M.,
Brossard J.H.,
GasconBarré M.,
D'Amour Pierre
Publication year - 1994
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.5650090506
Subject(s) - endocrinology , medicine , calcium , vitamin d and neurology , parathyroid hormone , stimulation , calcitriol , vitamin d deficiency , calcium metabolism , cholecalciferol , vitamin , chemistry
Abstract This study analyzes the parathyroid function in four dogs before and after 2 years of a low‐calcium, high‐sodium, vitamin D‐deficient diet and the involution of the same function following (1) correction of dietary calcium deficiency and administration of IV 1,25‐(OH) 2 D (0.25 μg twice per day) during 1 month, (2) after an additional month of normal dog chow supplemented with oral vitamin D (25 μg per day), and, finally, (3) after 5 and 17 months of a diet with normal levels of calcium and vitamin D. The parathyroid function was evaluated through IV infusion of CaCl 2 and Na 2 EDTA with measurement of intact (I) and carboxyl‐terminal (C) immunoreactive parathyroid hormone ( i PTH). The C‐ i PTH/I‐ i PTH ratio was calculated to assess the modulation of molecular forms of i PTH induced by the various treatments. The 2 years of calcium and vitamin D deprivation lowered ionized calcium (1.23 ± 0.04, p < 0.05) and 25‐OHD (4.02 ± 2.06 nM, p < 0.005) and tended to decrease 1,25‐(OH) 2 D (80.8 ± 8.6 pM); it increased basal I‐ and C‐ i PTH levels approximately eightfold (I‐ i PTH, 40.2 ± 20.7, p < 0.05; C‐ i PTH, 185.4 ± 94.9, p < 0.05) and stimulated I‐ i PTH (60.2 ± 23.0 pM, p < 0.05) and C‐ i PTH (239.6 ± 80.7 pM, p < 0.05) fivefold. A greater rise in nonsuppressible I‐ i PTH levels than in C‐ i PTH levels led to a decreased C‐ i PTH/I‐ i PTH ratio in hypercalcemia (12.5 ± 2.8 versus 27.8 ± 6.05 pM, p < 0.005). Dietary deprivation also decreased the I‐ i PTH calcium stimulation set point (1.25 ± 0.05 pM, p < 0.05). Treatment with dietary calcium and IV 1,25‐(OH) 2 D normalized ionized calcium (1.34 ± 0.02 mM) and basal I‐ i PTH level (6.09 ± 5.48 pM) more than basal C‐ i PTH (69.8 ± 48.8 pM), causing the C‐ i PTH/I‐ i PTH ratio to increase from 4.80 ± 0.81 to 14.8 ± 6.1 ( p < 0.05). Stimulated I‐ i PTH decreased (46.1 ± 15.3 pM, p < 0.05), but stimulated C‐ i PTH secretion did not change (282.4 ± 90.9 pM). A greater fall in the nonsuppressible I‐ i PTH level as opposed to C‐ i PTH level led the C‐ i PTH/I‐ i PTH ratio to increase back to a normal value (23.8 ± 1.40). The I‐ i PTH calcium stimulation set point remained low at 1.28 mM. Further consecutive treatment modalities over 18 months did not cause additional significant change in basal, stimulated, or nonsuppressible C‐ i PTH levels, but the same I‐ i PTH levels tended to decrease further. This explained why all three C‐ i PTH/I‐ i PTH ratios tended either to increase (basal) or to increase significantly (stimulated and nonsuppressible, p < 0.05). The I‐ i PTH calcium stimulation set point again remained low. This study reveals that animals with hyperplastic parathyroid glands can control their I‐ i PTH level by maintaining a lower set point of I‐ i PTH stimulation by calcium and by changing their secretion profile with respect to carboxyl‐terminal fragments of the PTH molecule.