Serum vitamin D levels may not reflect tissue-level vitamin D in sarcoidosis.

Hypercalcemia in sarcoidosis is due to three mechanistic reasons: (1) systemic conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by the enzyme 1-α hydroxylase produced by activated monocyte/macrophage system, (2) production of parathormone-related peptide (PTHrP) by the sarcoid granuloma, (3) tissue-level conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by 1-αhydroxylase produced by local monocyte/macrophage system in the sarcoid granuloma. We report two cases of one proposed mechanism of hypercalcaemia in sarcoidosis (mechanism 3). Both individuals presented with sarcoidosis and 25-hydroxyvitamin D deficiency and developed symptomatic hypercalcaemia with vitamin D replacement. Given their low serum parathormone and parathormone-related peptide levels, low serum 25-hydroxy vitamin D and normal serum 1,25-dihydroxyvitamin D, the systemic 25-hydroxy vitamin D deficiency may not have reflected an increased activity of vitamin D at the local granulomatous tissue level.