Vitamin D Metabolism after PTH Therapy in Hypoparathyroidism

Chronic hypoparathyroidism (hypoPT) is a rare disease characterized by insufficient parathyroid hormone (PTH) production/secretion, usually secondary to damage or removal of the parathyroid glands during head and neck surgery and often associated with hypocalcaemia and other clinical findings. Until recently, standard therapy for this disorder consisted of calcium and vitamin D analog supplementation frequently associated with hypercalciuria, potentially resulting in long-term renal complications such as nephrocalcinosis, nephrolithiasis, and renal insufficiency. Recently, it has been shown that daily subcutaneous doses 20μg of recombinant human PTH(1-34) or 50-100 µg rhPTH(1-84) (NatPar), were effective in maintaining serum calcium concentrations and enabling significant decreases in vitamin D analog and oral calcium doses. We present preliminary data from a follow-up study, comparing vitamin D metabolism in patients on standard treatment (n=7) vs PTH (n=7). Group comparison was performed for adjusted calcium (ACa), phosphate (PO4), 25(OHD), 1,25(OH)2D and 24,25(OH)2D using a Mann Whitney U tests (IBM SPSS version 25.0.0.1) at baseline and after 2, 4, 6, 8, 12 and 16 weeks of either treatment. Within group comparison were performed using ANOVA with Bonferroni post-hoc using SPSS. ACa, PO4 and 25(OH)D did not show any significant differences between the two treatments at any time point. In both cases. ACa increased within the reference range (2.1-2.5 mmol/L) and PO4 decreased to mid reference range (0.8-1.5 mmol/L). 25(OH)D concentrations decreased while those of the active form 1,25(OH)2D increased from baseline when treated with PTH achieving significant difference after 16 weeks of daily injections of PTH. 24,25(OH)2D was significantly decreased in patients treated with PTH, resulting in a significant (p<0.05 after 8 weeks of treatment) difference of the ratios 25:24,25 and 1,25:24,25 vitamin D, while standard treatment with calcium and vitamin D showed no significant effect on these ratios. In patients with HypoPT, daily injection of PTH induced a significant (ANOVA, p<0.05) increase of 1,25(OH)2D concentrations, by activating 1-alpha hydroxylase (CYP27B1) in the kidney and by decreasing the degradation of 25(OH)D to 24,25(OH)2D by CYP24A1. Lower concentrations of 24,25(OH)2D may also increase the number of available vitamin D receptors for 1,25(OH)2D resulting in beneficial effects such as faster and greater decrease of PO4 and increase of ACa.