CHRONIC ADAPTATION OF DOG PARATHYROID FUNCTION TO A LOW-CALCIUM-HIGH-SODIUM-VITAMIN-D-DEFICIENT DIET

The development of secondary hyperparathyroidism was studied in relation to changes in serum ionized Ca (Ca2+), 25-OHD, and 1,25-(OH)2D concentrations in six dogs maintained on a low-Ca (0.05%), high-Na (1.6%), and vitamin D-deficient diet for 91 weeks. Blood samples and evaluations of the parathyroid function were obtained before and after 3, 12, 24, 36, and 91 weeks of diet. Serum iPTH was measured by an intact hormone (I) and a carboxy-terminal (C) assay. The sigmoidal relationship between ionized Ca and iPTH values was evaluated mathematically. Results are means +/- SD. Statistically significant changes over a time period were evaluated by an ANOVA for repeated messurements. Over the first 3 weeks, serum Ca2+, 25-OHD, and 1,25-(OH)2D did not change but stimulated I-iPTH increased 84.3 +/- 39.9% (p < 0.005) and C-iPTH only 25.3 +/- 12.2% (p < 0.01), a significant difference (p < 0.02). The increase in stimulated I-iPTH reached 487.4 +/- 139.6% (p < 0.0001) and 418.4 +/- 76.9% (p < 0.0001) for C-iPTH by the end of the study. Similar significant increases were seen in basal and nonsuppressible iPTH at or after week 12. Serum 25-OHD concentration had decreased significantly at 12 weeks (0 = 99.9 +/- 28.3 to 12 = 40 +/- 6.8 nM, p < 0.005) and even more so at 91 weeks (4.1 +/- 0.3 nM, p < 0.0005); this could be related to stimulated I-iPTH at 12 weeks (r = -0.5472, p < 0.02) and thereafter, even though 25-OHD does not have a direct effect on the parathyroid glands. Even if serum Ca2+ had only decreased at week 36 (0 = 1.36 +/- 0.02 to 36 = 1.32 +/- 0.02 mM, p < 0.05), it could be inversely related to stimulated I-iPTH from week 24 (r = -0.4290, p < 0.05). Serum 1,25-(OH)2D increased up to 24 weeks (0 = 109.7 +/- 20.7 to 24 = 173.4 +/- 28.7 pM, p < 0.0005) at which time it was positively related to stimulated I-iPTH (r = 0.506, p < 0.02); it then decreased to slightly below basal level by week 91 (82.7 +/- 8.6 pM). Despite these two added stimuli, progression of the parathyroid function did not accelerate after week 24. In conclusion, dietary changes appear to be the main factor stimulating secondary hyperparathyroidism in this model. The addition of a low serum Ca2+ and a relatively low level of 1,25-(OH)2D did not enhance the effect of the diet.