To D or not to D should clinicians be encouraged to replace vitamin D when managing patients with primary hyperparathyroidism?

Manish Modi, Channa N Jayasena, F Palazzo, Mandy Donaldson, K Meeran, Waljit S Dhillo


BACKGROUND: Vitamin D deficiency is routinely discovered in patients with primary hyperparathyroidism (PHP). However, clinicians are reluctant to correct vitamin D levels in these patients, particularly due to concerns about aggravating hypercalcaemia and hypercalciuria. Furthermore, there is insufficient evidence available on the effect of vitamin D on the biochemical derangements observed in patients with PHP.

AIM: To determine the relationship between 25(OH) vitamin D status and biochemical markers in patients with PHP.

METHODS: We conducted a large retrospective study of 251 patients diagnosed with PHP using clinical, biochemical, radiological and histological criteria. Approximately 1000 biochemical measurements for plasma parathyroid hormone (PTH), serum phosphate, albumin-adjusted serum calcium and 24-hour total urine calcium excretion, and calculated values for urine calcium-to-creatinine ratio (UCCR) were collated. We excluded patients with renal failure, or those on thiazides or lithium.

RESULTS: In patients with PHP, serum 25(OH) vitamin D was correlated negatively with plasma PTH (r=-0.17,p<0.0001), and correlated positively with serum phosphate (r=0.13,p<0.0001) and urine calcium (r=0.18,p<0.001). Patients with co-existing vitamin D deficiency displayed the most severe PTH hypersecretion (mean plasma PTH in pmol/L: 18.90.7, 25(OH)D<25nmol/L; 15.00.4, 25(OH)D>25nmol/L; p<0.001) and most severe phosphate wasting (mean serum phosphate in mmol/L: 0.860.01, serum 25(OH)D<25nmol/L; 0.910.006, serum 25(OH)D>25nmol/L; p<0.001). However, mean hypercalcaemia remained unaltered by serum 25(OH) vitamin D status (mean serum calcium in mmol/L: 2.710.01, 25(OH)D<25nmol/L; 2.700.006, 25(OH)D>25nmol/L; p=0.26). UCCR values were also significantly lower in patients with co-existing vitamin D deficiency (mean UCCR: 0.01810.0008, 25(OH)D<25nmol/L; 0.02160.0006, 25(OH)D>25nmol/L; p<0.001).

CONCLUSION: Our data suggests that vitamin D deficiency in patients with PHP is associated with more severe derangements in PTH and phosphate levels, and reduced diagnostic accuracy of UCCR. Furthermore, greater vitamin D levels were not associated with worsened hypercalcaemia. We therefore recommend that vitamin D replacement should be considered in patients with PHP and coexistent vitamin D deficiency.