Endocrine Shades of Silicone Fillers: A Case of Calcitriol-mediated Hypercalcemia.

Background: The inflammatory reaction of foreign body granulomas (FBG) may be so vast that it leads to severe systemic effects.

Case Report: A 42-year-old woman was referred to the ED with severe recurrent symptomatic hypercalcemia associated with worsening kidney function. She had presented multiple times with similar complaints. Severe hypercalcemia (13.8 mg/dL) was noted, with appropriately low PTH, elevated PTHrP, low 25-hydroxyvitamin D, and normal 1,25-dihydroxyvitamin D levels. She admitted having significant subcutaneous silicone filler injections in the hips six years prior. Admission workup revealed a normal 25-hydroxyvitamin D, but a marked elevation of 1,25-dihydroxyvitamin D (138 pg/mL). Whole-body PET-CT demonstrated moderate 2-18F-fluoro-2-deoxy-d-glucose (FDG) uptake within the subcutaneous adipose tissue of the lateral aspects of the gluteal regions. She was diagnosed with silicone filler injection-induced hypercalcemia, secondary to granulomatous inflammation. Her calcium level normalized a month after the initiation of prednisone.

Discussion: FBG may occur years after filler injection. In rare cases, a significant granulomatous immune response leads to uncontrolled production of calcitriol. Pro-inflammatory cytokines can also upregulate PTHrP expression in macrophages, further contributing to hypercalcemia. Treatment focuses on general hypercalcemia management and FBG remission, most effectively achieved with anti-inflammatory corticosteroid doses. Nevertheless, further studies are needed to evaluate its long-term treatment efficacy.

Conclusion: Granulomatous inflammation from silicone filler injection can cause hypercalcemia by uncontrolled production of calcitriol and increased PTHrP production by macrophages and giant cells.