Title: 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
Abstract: 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)2D (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 CaCl2 and Na2 EDTA with measurement of intact (I) and carboxyl-terminal (C) immunoreactive parathyroid hormone (iPTH). The C-iPTH/I-iPTH ratio was calculated to assess the modulation of molecular forms of iPTH 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)2D (80.8 ± 8.6 pM); it increased basal I- and C-iPTH levels approximately eightfold (I-iPTH, 40.2 ± 20.7, p < 0.05; C-iPTH, 185.4 ± 94.9, p < 0.05) and stimulated I-iPTH (60.2 ± 23.0 pM, p < 0.05) and C-iPTH (239.6 ± 80.7 pM, p < 0.05) fivefold. A greater rise in nonsuppressible I-iPTH levels than in C-iPTH levels led to a decreased C-iPTH/I-iPTH ratio in hypercalcemia (12.5 ± 2.8 versus 27.8 ± 6.05 pM, p < 0.005). Dietary deprivation also decreased the I-iPTH calcium stimulation set point (1.25 ± 0.05 pM, p < 0.05). Treatment with dietary calcium and IV 1,25-(OH)2D normalized ionized calcium (1.34 ± 0.02 mM) and basal I-iPTH level (6.09 ± 5.48 pM) more than basal C-iPTH (69.8 ± 48.8 pM), causing the C-iPTH/I-iPTH ratio to increase from 4.80 ± 0.81 to 14.8 ± 6.1 (p < 0.05). Stimulated I-iPTH decreased (46.1 ± 15.3 pM, p < 0.05), but stimulated C-iPTH secretion did not change (282.4 ± 90.9 pM). A greater fall in the nonsuppressible I-iPTH level as opposed to C-iPTH level led the C-iPTH/I-iPTH ratio to increase back to a normal value (23.8 ± 1.40). The I-iPTH 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-iPTH levels, but the same I-iPTH levels tended to decrease further. This explained why all three C-iPTH/I-iPTH ratios tended either to increase (basal) or to increase significantly (stimulated and nonsuppressible, p < 0.05). The I-iPTH calcium stimulation set point again remained low. This study reveals that animals with hyperplastic parathyroid glands can control their I-iPTH level by maintaining a lower set point of I-iPTH stimulation by calcium and by changing their secretion profile with respect to carboxyl-terminal fragments of the PTH molecule.
Publication Year: 1994
Publication Date: 1994-05-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 33
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