(11.06) The Price of Beauty: Resistant PTHrP-mediated Hypercalcemia due to silicone injections

1-25 vitamin D mediated hypercalcemia is a rare but well-described complication of injectable silicone, usually due to the formation of granulomas at the injection sites. We report a case of PTHrP-mediated hypercalcemia likely due to silicone injections.

Case(s) Description :

A 44-year-old male with a past medical history of HIV, CKD Stage 4, nephrolithiasis, and hypertension presented with altered mental status. Work up was significant for acute kidney injury (Cr 3.72 mg/dl) in the setting of moderate hypercalcemia (corrected Ca²⁺ 13.7 mg/dl, ionized Ca²⁺  1.7 mmol/L), hypercalciuria (24-hr urine Ca²⁺ 525 mg/24 hour), and vitamin D deficiency (25-OH vitamin D 19 ng/ml). Parathyroid hormone was normal (PTH 37 PG/ML) in the setting of hypercalcemia. Hypercalcemia was present since 2019, and labs at that time showed normal renal function. He was treated with intravenous fluids, pamidronate and Vitamin D. Further evaluation revealed an elevated parathyroid hormone-related peptide (PTHrP 5.8 pmol/L), normal 1,25 Dihydroxy Vitamin D, normal ACE concentration, and normal SPEP. CT abdomen and pelvis showed extensive calcium deposits of the bilateral gluteal region and proximal thighs. On further questioning, he reported receiving silicone injections to his hips 25 years prior. CT Chest showed no evidence of sarcoidosis. PET/CT showed moderate diffuse uptake throughout the subcutaneous fat of the flanks and proximal thighs with the highest SUV value 3.04 and no evidence of malignancy. It was concluded that the hypercalcemia was secondary to silicone induced granulomas. He received denosumab 60 mg, but hypercalcemia returned 2 months after. His care has been complicated by resistant hypercalcemia, recurrent nephrolithiasis, and worsening renal function.

Discussion :

Silicone-mediated granuloma formation has been reported in up to 20% among those receiving injections, with variable onset from three weeks to 20 years after injection. Most reports of silicone associated hypercalcemia were due to elevated 1-25 vitamin D concentrations. In our case, only PTHrP was elevated. Of note, the assay for PTHrP was not affected by CKD. 1-25 vitamin D was possibly falsely normal due to underlying chronic kidney disease. Similarly, PTH was not fully suppressed likely due to CKD. No alternate cause of hypercalcemia was found thus the diagnosis of silicone induced hypercalcemia was made. This case serves as a reminder of the importance of thorough history taking and incorporating the physiological changes in CKD in the interpretation of the diagnostic evaluation of hypercalcemia.