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

Abstract

Background: Vitamin D deficiency is increasingly recognized in patients with primary hyperparathyroidism but some clinicians are reluctant to replace vitamin D due to concerns with aggravating hypercalcaemia. We investigated the impact of vitamin D repletion in asymptomatic patients with normocalcaemic and hypercalcaemic primary hyperparathyroidism. Methods: This is a retrospective analysis of 111 patients with elevated parathyroid hormone concentrations (>6.4 pmol/L) referred to our endocrine clinic between January and December 2012; we identified 39 patients with primary hyperparathyroidism and vitamin D deficiency, i.e. 25 hydroxy vitamin D <20 mg/L. Patients were categorized into normocalcaemic (n ¼ 23) and hypercalcaemic (n ¼ 16) groups and the impact on biochemical parameters was recorded after at least six months treatment with either 1600 or 3200 units daily of cholecalciferol. Results: Both normocalcaemic and hypercalcaemic groups showed a rise in 25 hydroxy vitamin D concentrations after replacement (p <0.0001). Parathyroid hormone concentrations fell in the normocalcaemic group (p ¼ 0.08) but individually, five patients showed a rise (8-38% of baseline). In the hypercalcaemic group, parathyroid hormone remained static but the adjusted calcium concentration fell significantly (p ¼ 0.006) except in two patients who showed mild rises (3 and 6%, respectively). There was no deterioration in renal function or calcium-related adverse events in any of the groups. Conclusions: Our study supports the safety of vitamin D replacement in patients with mild asymptomatic primary hyperparathyroidism and coexistent vitamin D deficiency. Repletion does not aggravate hypercalcaemia and may limit disease progression. Patients with normocalcaemic primary hyperparathyroidism need further characterization from longitudinal studies.

Resolution of hypercalcemia in primary hyperparathyroidism with vitamin D replacement

“…3 However, studies suggest that vitamin D supplementation reduces PTH without adversely affecting serum calcium. 6 Other cases have reported on a small proportion of patients who experience slightly elevated calcium levels after vitamin D treatment. Due to patient variability, long-term clinical follow-up and longer duration of treatment are necessary.…”

Low 25‐Hydroxyvitamin D in Primary Hyperparathyroidism: Enhanced Conversion Into 1,25‐Hydroxyvitamin D May Not Be “True” Deficiency

“…The presence of low serum 25OHD in subjects with PHP is wellestablished. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) However, concurrently elevated serum 1,25 (OH)D concentrations in subjects with PHP have rarely been reported in the past 30 years. (15)(16)(17) This study also found normalization of mean concentrations of serum calcium, 25OHD, and 1,25(OH)D following a decline in circulating serum PTH levels after surgery.…”

“…This study also found a further rise in serum calcium on normalization of serum 25OHD consistent with most previous reports. (1,2,6,(15)(16)(17)20,21) In contrast, an isolated study has documented a lack of exaggerated rise in already existent hypercalcemia upon vitamin D supplementation. (12) However, in this study, 25OHD remained subnormal probably because of inadequate supplementation.…”

“…S ubnormal serum 25OHD concentrations are reported to occur frequently in individuals with primary hyperparathyroidism (PHP) and are attributed to concurrent vitamin D deficiency. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) It is plausible that the prevalence of vitamin D deficiency is overestimated and exaggerated because low serum 25OHD levels may be explained by its enhanced conversion into 1,25-hydroxyvitamin D [1,25(OH)…”

Elevated PTH with normal serum calcium level: a structured approach

“…2,16,18 In a 2015 study that included 23 patients with PHPT, vitamin D deficiency and normal calcium, 6 months' treatment with 1600-3200 IU per day did not provoke hypercalcaemia. 19 What is the clinical context for the patient with normocalcaemic hyperparathyroidism?…”