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

Abstract

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.

Keywords: Calcitriol; Hypercalcemia; PTHrP; Silicone-induced granuloma.

Fig. 1

Skin findings noted in right hip on physical exam.

Fig. 2

Total body fluorodeoxyglucose positron emission tomography (PET)/CT scan. Panel A: Anteroposterior view. Panel B: Right lateral view. Noted diffuse moderate FDG uptake in the subcutaneous adipose tissue of bilateral gluteal regions greatest laterally extending inferiorly to the level of the hips and upper thighs, measuring on the order 31 cm in superior to inferior extent bilaterally. The left-side area has a SUV max of 4.9, and the right-side area has SUV max of 5.4.