MON-778 - Severe Hypercalcemia Presenting as Altered Mental Status in Silicone-Induced Granulomatous Disease

Introduction: Hypercalcemia is a potentially life-threatening condition with a broad differential. Granulomatous diseases can cause non–PTH-mediated hypercalcemia through extrarenal calcitriol production, classically seen in sarcoidosis and tuberculosis. Silicone-induced granulomatous disease has been described; however, clinically significant and symptomatic cases remain exceptionally uncommon. We report a case of severe hypercalcemia presenting as altered mental status due to silicone granulomatosis.

Case presentation: This is a 58-year-old female with medical history of hypertension, who presented with altered mental status and hypertensive crisis. Initial laboratory evaluation showed a total calcium of 16.7 mg/dL, ionized calcium of 7.4 mmol/L, and suppressed parathyroid hormone (PTH) at 9 pg/mL. Additional studies demonstrated phosphate 3.2 mg/dL, elevated 25-hydroxyvitamin D >200 ng/mL, and TSH at 1.63 µIU/mL. CT chest abdomen and pelvis with IV contrast showed a right 5 x 4 x 12 mm obstructing calculus with mild hydroureteronephrosis and diffuse edema of bilateral gluteal regions. Given concerns for non–PTH-mediated hypercalcemia, a multidisciplinary evaluation was initiated. Further workup revealed PTH–related peptide (PTHrP) 14 pg/mL, elevated angiotensin-converting enzyme (ACE) level at 151 U/L, increased 1,25-dihydroxyvitamin D at 105 pg/mL, and serum protein electrophoresis negative for monoclonal paraproteinemia. A skeletal survey demonstrated extensive soft tissue calcifications in the bilateral proximal thighs and gluteal regions, raising concern for silicone-induced granulomas. Patient disclosed taking vitamin D 50,000 IU daily for several weeks and reported prior cosmetic silicone injections to the buttocks more than 25 years earlier. Calcium levels remained persistently elevated despite IV fluids, calcitonin, IV bisphosphonate, and Denosumab injections. A left gluteal biopsy subsequently confirmed silicone granulomatosis. The patient was treated with prednisone 40 mg daily with a gradual taper and ketoconazole 400 mg twice daily, resulting in significant improvement in serum calcium levels. Close outpatient follow-up was recommended to discuss tumor necrosis factor–alpha inhibition and potential surgical debulking.

Conclusion: Hypercalcemia associated with granulomatous reactions to silicone injections is uncommon but may be severe, occurring in an estimated 1–4% of patients with siliconomas. The pathophysiology involves dysregulated extrarenal calcitriol production by activated macrophages within granulomatous tissue. Treatment focuses on suppressing granulomatous inflammation and correcting hypercalcemia. A high index of clinical suspicion and coordinated multidisciplinary care are essential for timely diagnosis and optimal outcomes.

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