Vitamin D Supplementation in Granulomatous Disease: Why Individualized Assessment May Be Safer Than Universal Thresholds.

Vitamin D deficiency is commonly identified and treated according to serum 25-hydroxyvitamin D (25(OH)D) concentrations. In granulomatous disease, however, this approach may be insufficient because activated macrophages within granulomatous tissue convert 25(OH)D to the active metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D) through extrarenal 1alpha-hydroxylase activity. A patient may therefore have a low 25(OH)D concentration while simultaneously having preserved or increased active vitamin D activity, creating a risk of hypercalcemia or hypercalciuria when vitamin D is supplemented. This editorial argues that vitamin D replacement in granulomatous disease should be individualized rather than governed by a universal supplementation limit. Serum 1,25(OH)2D should be an important component of the assessment, but it should not be used as a solitary treatment threshold. Serum calcium, renal function, urinary calcium when clinically appropriate, the activity and phenotype of the granulomatous disease, and the indication for vitamin D replacement should also be considered. Current evidence and the American Thoracic Society guideline support assessment of both vitamin D metabolites when replacement is being considered in sarcoidosis, while acknowledging limitations in the evidence base. An individualized approach may better balance the potential skeletal benefits of correcting vitamin D deficiency against the risk of vitamin D-mediated hypercalcemia. Prospective studies are needed to determine whether metabolite-guided supplementation can improve clinical outcomes.