SUN-776 - Ketoconazole Use for Calcitriol-Mediated Hypercalcemia in Silicone Granulomas

Introduction:
Liquid silicone continues to be used in non-medical settings despite being banned by the Food and Drug Administration due to catastrophic side effects, including migration, deformity, and death. A major complication is silicone-induced foreign body granulomas (SFBG), which can cause hypersensitivity reactions with debilitating pain and, rarely, calcitriol-mediated hypercalcemia.

Case Description:
A 55-year-old female was referred for severe hypercalcemia with corrected serum calcium (cCa) of 14.5 mg/dL (normal 8.7–10.2). History revealed silicone injections to the gluteal area (2002–2003). Over subsequent years, she reported intermittent induration, pain, warmth, and erythema in this area. She reported mood changes, fatigue, confusion, polyuria, and history of nephrolithiasis. Laboratory showed suppressed parathyroid hormone (PTH) (7 pg/mL; normal 14-72) and elevated 1,25-dihydroxyvitamin D3 (108 pg/mL; normal 24.8-81.5), with normal 25-hydroxyvitamin D3 levels (37 ng/mL; normal 30-100 ng/mL). CT imaging demonstrated extensive bilateral contrast-enhancing lesions with muscle infiltration. These areas were highly hypermetabolic on PET-CT scan, consistent with a diagnosis of SFBG.

Prednisone 30 mg daily was initiated. Due to persistent hypercalcemia (cCa 11.7–12.3), treatment was switched to dexamethasone up to 6 mg daily, improving cCa (12.3 → 9.8 mg/dL) and calcitriol (101 → 47 pg/mL). However, the patient expressed concerns about long-term steroid use. Therefore, ketoconazole 200 mg twice daily was initiated with steroid taper. cCa stabilized between 9.5–10.4 mg/dL with normalization of calcitriol (39.6 pg/mL). One month later, ketoconazole dose was reduced to 200 mg daily due to mild elevation in liver function tests. At 6-month follow-up, the patient remains asymptomatic with stable normocalcemia and is undergoing evaluation for surgical management.

Unique Features/Teaching Points:
Calcitriol-mediated hypercalcemia is a condition in which the gold-standard treatment includes management of the underlying cause. This is particularly challenging in cases of SFBG, especially in the context of a large granulomatous volume and limited surgical expertise. Therefore, medical treatment is often needed, given the consequences of long-term uncontrolled hypercalcemia. Long-term glucocorticoid therapy is often not feasible due to long-term adverse effects. This case demonstrates that low-dose ketoconazole, by inhibiting extrarenal 1α-hydroxylase, can safely maintain eucalcemia in SFBG. Therefore, ketoconazole may serve as an effective steroid-sparing bridging therapy in patients awaiting definitive surgical treatment.

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