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

Abstract

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.

An unexpected cause of severe and refractory PTH-independent hypercalcemia: case report and literature review

“…In our patient, hypercalcemia was very probably mediated by calcitriol, as serum PTH and PTHrp levels were not detectable (5).…”

Physicochemical characterization of inorganic deposits associated with granulomas in cutaneous sarcoidosis

“…Calcium oxalate and phosphate deposits have been reported in sarcoidosis, however, to the best of our knowledge, we report the first cases of calcite deposits . Presence at the nanometre scale of these deposits, including in patients with normal serum calcium level, raises the question that calcium carbonate deposits in tissues around granulomas could be a common not yet highlighted finding in conjunction with the role of the granuloma in vitamin D and calcium metabolism …”

“…19 Presence at the nanometre scale of these deposits, including in patients with normal serum calcium level, raises the question that calcium carbonate deposits in tissues around granulomas could be a common not yet highlighted finding in conjunction with the role of the granuloma in vitamin D and calcium metabolism. 20 In conclusion, such a study needs to be extended to samples from other organs affected by sarcoidosis, mostly lung and mediastinal lymph nodes exposed to environmental and occupational pollutants. Moreover, the consequence of calcite deposits in organs where granulomas develop should be investigated.…”

Disparities in Head and Neck Cancer: A Case for Chemoprevention with Vitamin D

“…As discussed above, circulating levels of vitamin D in humans have been targeted at >30 ng/mL (75 nmol/L or 0.075uM) [33] for optimal health. However, precise dose extrapolation from cell lines to physiological relevant human concentrations of vitamin D is complicated by the fact that levels may not accurately reflect tissue or intracellular concentrations [34]. Furthermore, human intervention studies or supplementation in free-living populations frequently involve daily vitamin D intake or in some intervention studies multiple times a day, whereas the in vitro studies herein are based on a single dose of vitamin D. Considering these factors a concentration of 2 µM was chosen for all cell-based assays.…”