Biochemical effects of calcifediol supplementation in mild, asymptomatic, hyperparathyroidism with concomitant vitamin D deficiency

Abstract

It has been proposed to cautiously supplement with vitamin D to any patient with asymptomatic primary hyperparathyroidism (PHTP) and a plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/l. Evidence about the safeness of this intervention is limited to two studies. Our aim was to prospectively assess the biochemical effects of one-year 25(OH)D supplementation in this context. Twenty-seven patients were included in this study. Calcifediol was started at a dose of 480-960 IU/24 h (8-16 microg/24 h) and adjusted up to a maximum of 960 IU/24 h (16 microg/24 h). Basal calcium, phosphate, albumin, total alkaline phosphatase (ALP), creatinine, 24 h calcium urinary excretion, intact PTH (iPTH) and 25(OH)D were measured before and during vitamin D supplementation. The mean basal 25(OH)D was 28.7 +/- 8.0 nmol/l, and at 12 months was 71.5 +/- 32.5 nmol/l (P = 0.00 vs. baseline). After 3, 6 and 12 months iPTH levels were 141.7 +/- 108.4 ng/l (P = 0.00 vs. baseline), 131.1 +/- 95.7 ng/l (P = 0.03 vs. baseline) and 162.2 +/- 139.3 ng/l (P = ns vs. baseline). Mean calcium did not change. Mean urinary calcium excretion increased significantly (basal: 5.7 +/- 2.9 mmol/24 h, 12 months: 7.9 +/- 4.9 mmol/24 h, P = 0.02). Cautious calcifediol supplementation significantly increased mean 25(OH)D and temporarily reduced mean iPTH. It did not change mean serum calcium, but urinary calcium excretion increased significantly. We suggest that serum calcium and 24 h calciuria be measured at regular intervals in patients with PHTP, while on calcifediol supplementation.

Current evidence for recommendation of surgery, medical treatment and vitamin D repletion in mild primary hyperparathyroidism

“…Tucci (67) could not substantiate any risk of vitamin D 2 treatment in PHPT at doses up to 2500 mg/month. Plasma creatinine levels and the occurrence of renal stones were not reported in these studies (65)(66)(67)(68).…”

“…However, the decrease was no longer significant after 1 year of treatment (19.7G14.2 vs 17.2G14.6 pmol/l, NS). Average plasma calcium levels remained unchanged at 3 months (2.70G0.13 mmol/l), 6 months (2.73G 0.10 mmol/l) and 12 months (73G0.10 mmol/l) (68).…”

Impact of vitamin D replacement in patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism and coexisting vitamin D deficiency

“…18 Several other studies in comparable patient groups with PHPT and vitamin D deficiency have similarly reported stable calcium concentrations with or without an increase in urinary calcium in response to various doses of vitamin D supplements. 17,25 More recently, Wagner et al 19 assigned patients to treatment with either 1000-2000 IU daily or 50,000 IU weekly of vitamin D. PTH concentrations were unchanged in both groups and calcium concentrations remained stable in the high dose group but decreased in the low dose group although this became statistically insignificant after multiple adjustments for age, sex, vitamin D, and PTH concentrations. Lastly, Ranganathan et al also showed that in postmenopausal female with PHPT and coexisting vitamin D deficiency prolonged treatment with vitamin D reduced serum PTH concentration with no adverse effects on adjusted serum calcium concentrations and renal function.…”

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

“…Few data are available on the effect of vitamin D repletion in PHPT patients; increase in urinary calcium excretion has been reported, though with no evidence of kidney stones development (20,21,22). A recent interventional study in PHPT patients with coexistent vitamin D deficiency showed that vitamin D replacement increases serum 25-hydroxyvitamin D levels and reduces serum PTH without causing hypercalcaemia and hypercalciuria (23).…”