Muscle-Limited Sarcoidosis Presenting as Recurrent Hypercalcemia of Unknown Origin

Introduction: Hypercalcemia is a commonly encountered clinical entity, affecting approximately 1-2% of the general population. Elevation of the parathyroid hormone (PTH), parathyroid hormone related peptide (PTHrP) or vitamin D is frequently observed in these cases. Most often, hypercalcemia is caused by elevated parathyroid hormone (PTH) levels; however, there is a broad differential for hypercalcemia. Occasionally, the cause of hypercalcemia is not apparent despite extensive work-up. We present a case of a young woman with severe and recurrent hypercalcemia of unknown origin. Case Description: An18-year-old Amish female with history of hypothyroidism secondary to childhood thyroid toxicosis, Raynaud’s disease, fibromyalgia, and spina bifida presented for evaluation of recurrent hypercalcemia. She initially presented to her community naturopathic healer after developing myalgias, fevers, night sweats, and constipation. Six months later, her symptoms worsened, and she presented to our institution. Evaluation revealed AKI with sCr 1.69mg/dL, hypercalcemia with Ca 16 mg/dL, low-normal phosphorus of 2.7mg/dl, suppressed PTH at 5pg/ml, undetectable PTHrP, low 25-vitamin D of 10ng/dL, and normal 1, 25-vitamin D of 66pg/mL. 24-hour urinary calcium was elevated at 310 mg. Additional work up including evaluation for paraprotein disease, vitamin A levels, bone marrow biopsy, and skeletal survey were all negative. After medical management with intravenous fluids and bisphosphonate she was discharged. The patient had recurrent hospital admissions with severe hypercalcemia. It was noted that she had again had normal 1-25 vitamin D levels and an elevated 24:24,25-vitamin D ratio of 33, despite very elevated intact FGF-23 of 352pg/mL, suggesting a non-regulated production of 1-25 vitamin D. Genetic investigations were negative for CYP24A1, SLC34A1 and ALPL mutations. In a search for the occult source of 1-25 vitamin D, the levels of angiotensin converting enzyme and aldolase were found to be elevated, with positive uptake noted at her shoulder in a PET scan suggestive of muscle limited sarcoidosis. She was started on plaquenil with resolution of hypercalcemia. Discussion: We present a case of occult hypercalcemia, ultimately ascribed to muscle limited sarcoidosis which responded to Plaquenil. The case illustrates the interpretation of hormonal parameters in a challenging case of hypercalcemia.