Hypercalcemia Due to Statin-Induced Sarcoid-Like Reaction

Introduction: Drug-induced sarcoid-like reactions (DISR) are systemic granulomatous reactions which are indistinguishable from sarcoidosis except DISR often resolves with discontinuation of the offending drug. We present the first suspected case of DISR due to atorvastatin. Case Description: A 54-year-old man with chronic kidney disease was admitted for acute kidney injury (AKI) with hypercalcemia to 11.8 mg/dL and creatinine (Cr) 3.09 mg/dL (baseline 1.7). Thiazide and vitamin D had been discontinued months prior. Labs revealed suppressed parathyroid hormone (PTH), normal total and 25-OH-vitamin D, and normal PTH-related protein levels. Chest computed tomography (CT) showed mild mediastinal and possible bilateral hilar adenopathy, miliary nodules in both lungs, and many bilateral renal cysts. Serum IL-2 receptor alpha chain (IL-2RA), a biomarker with high sensitivity and specificity for sarcoidosis, was elevated to 5549 pg/mL. Serum angiotensin-converting enzyme (ACE) level was normal. Bronchoscopy with bronchoalveolar lavage and lymph node biopsy revealed a depressed CD4+ to CD8+ ratio of 0.22. The patient’s hypercalcemia and AKI improved with intravascular fluids. 3 weeks later, calcium and Cr worsened to 11.1 and 2.96 mg/dL, respectively. Atorvastatin was stopped due to case reports of associated hypercalcemia. 1 week later, calcium normalized to 10.1 mg/dL. A chest CT at 2 months noted decreased mediastinal adenopathy, and a second at 6 months showed resolving tree-in-bud changes. The patient was asymptomatic throughout, and calcium levels remained normal. Evaluation of the renal cysts led to a diagnosis of autosomal dominant polycystic kidney disease (ADPKD). Discussion: Our patient had lung imaging suggestive of sarcoidosis and elevated IL-2RA. While ACE was normal, ACE is a less sensitive marker for sarcoidosis. The abnormally low CD4+ to CD8+ ratio may be due to statins’ immune-attenuating effects. Both hypercalcemia and lung changes improved with atorvastatin discontinuation, supporting the drug’s role as the likely precipitant. Evaluation for neoplastic, infectious, and endocrinological etiologies of hypercalcemia was negative. ADPKD was felt to be unrelated: while the PKD1 gene product is involved in intracellular calcium signaling, mutations are not known to precipitate humoral hypercalcemia. In summary, we highlight atorvastatin as a possible cause for DISR.