vitamin D toxicity

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Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity.

Pettifor JM, Bikle DD, Cavaleros M, Zachen D, Kamdar MC, Ross FP.

Ann Intern Med. 1995 Apr 1;122(7):511-3.

http://www.annals.org/cgi/content/full/122/7/511

OBJECTIVE: To determine the serum level of free 1,25-dihydroxyvitamin D

[1,25-(OH)2D] in patients with vitamin D toxicity and to assess the in

vitro effect of differing concentrations of vitamin D metabolites on the

free serum levels of 1,25-(OH)2D. DESIGN: 1) A case study of patients

hospitalized with vitamin D toxicity after accidentally ingesting a

veterinary vitamin D concentrate and 2) an in vitro experiment in which

vitamin D metabolites in various concentrations were added to normal

serum and their effect was noted on percentage of free 1,25-(OH)2D.

PATIENTS: 11 patients (age range, 8 to 69 years) were studied 10 to 40

days after hospitalization for hypercalcemia. MEASUREMENTS: Serum total

25-hydroxyvitamin D (25-OHD) and 1,25-(OH)2D levels were measured by

radioreceptor assays. The percentage of free 1,25-(OH)2D was measured by

centrifugal ultrafiltration isodialysis and was used to calculate actual

free 1,25-(OH)2D levels. In the in vitro studies, vitamin D metabolites

[25-OHD; 24,25-(OH)2D; 25,26-(OH)2D; and 25-OHD-26,23 lactone] were

added to normal serum in concentrations expected to occur with vitamin D

toxicity. The percentage of free 1,25-(OH)2D was measured by

isodialysis. RESULTS: All patients presented with marked hypercalcemia

(mean calcium level, 3.99 +/- 0.33 mmol/L). Serum 25-OHD levels ranged

from 847 to 1652 nmol/L, and total 1,25-(OH)2D levels (mean, 106 +/- 86

pmol/L) were elevated in only three patients. The percentage of free

1,25-(OH)2D (mean, 1.023% +/- 0.366%) was elevated in all nine patients

in whom it was measured. Actual free 1,25-(OH)2D levels (mean, 856 +/-

600 fmol/L) were elevated in six of the nine patients. Total 1,25-(OH)2D

levels were correlated with 25-OHD levels (r = 0.66; P = 0.03), whereas

total and free 1,25-(OH)2D levels were highly correlated (r = 0.957; P <

0.001). In the in vitro studies, the percentage of free 1,25-(OH)2D

increased after 25-OHD or 24,25-(OH)2D was added. CONCLUSIONS: Although

the patients had normal or near-normal total 1,25-(OH)2D values, most

patients had elevated free 1,25-(OH)2D levels. These findings suggest

that elevated free 1,25-(OH)2D levels might play a role in the

pathogenesis of hypercalcemia in vitamin D toxicity.

PMID: 7872586

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