Undetectable serum calcidiol: not everything that glitters is gold

Area of Science:

• Endocrinology
• Nephrology
• Immunology

Background:

• Nutritional vitamin D deficiency has recognized adverse effects.
• Chronic tophaceous gout and chronic kidney disease (CKD) are common conditions.
• Vitamin D metabolism is complex and can be altered in certain disease states.

Observation:

• A patient with gout (CKD Stage 3/4) and undetectable calcidiol developed severe hypercalcemia after vitamin D supplementation.
• Despite supplementation, serum 25(OH) vitamin D remained in the normal range during the hypercalcemic event.
• Post-recovery, serum 1,25(OH)2 vitamin D was normal despite CKD and low serum 25(OH) vitamin D.

Findings:

• Gout tophi biopsies revealed macrophage expression of 25(OH) vitamin D 1α-hydroxylase.
• This suggests localized, increased vitamin D activation in granulomatous tissue.
• The patient's hypercalcemia was likely driven by this aberrant activation, not just supplementation levels.

Implications:

• Caution is advised when supplementing vitamin D in patients with granulomatous conditions and CKD.
• Increased 1α-hydroxylase activity in conditions like gout may necessitate individualized treatment approaches.
• Further research is needed to understand vitamin D dynamics in complex disease states.