SUN-777 - Particle Disease as A Rare Cause of 1,25-Dihydroxyvitamin D-Mediated Hypercalcemia

Introduction: Hypercalcemia is a common endocrinopathy seen in clinical practice. The most common cause of hypercalcemia is primary hyperparathyroidism, although non-parathyroid hormone (PTH) dependent hypercalcemia is also seen and elucidating its cause can be challenging. The known non-PTH dependent mechanisms are excessive production of ectopic PTH, PTH related peptide, or 1, 25-dihydroxyvitamin D (1,25-(OH)2 D). We present an unusual case of 1,25-(OH)2 D mediated hypercalcemia in a patient caused by microscopic debris from a prosthetic joint, a condition known as particle disease.

Case Report: A 68-year-old male with a past medical history of hypothyroid, hypertension, atrial fibrillation, and bilateral total knee and hip replacements in early 2020’s, presented with significant weight loss, lack of appetite, and worsening malaise. The patient’s initial diagnostic workup revealed elevated serum calcium at 13.5 mg/dL (8.3 - 10.8 mg/dL), suppressed PTH at 1 pg/mL (10 - 65 pg/mL), normal 25-hydroxyvitamin D at 83 ng/mL, PTH related peptide < 2 pmol/L (0 - 2.3 pmol/L), angiotensin converting enzyme at 42 U/L (16 - 85 U/L) and elevated 1,25-(OH)2 D of 174 pg/mL (59 - 79 pg/mL). Due to the patient’s markedly elevated calcium, he was treated with prednisone with dramatic and rapid normalization of calcium to 9.9 mg/dL. A CT scan was nondiagnostic. A PET scan demonstrated increased FDG uptake in multiple lymph nodes along the left external iliac chain, left common iliac chain, and left inguinal region with very intense periprosthetic uptake at the left knee. He underwent surgical revision of the left knee prosthesis and pathology showed chronic inflammation of the synovium with giant cell formation indicating a foreign body reaction. After removal of the prosthesis, the patient’s calcium and 1,25-(OH)2 D have since normalized with complete resolution of his symptoms.

Discussion: Excess endogenous 1,25-(OH)2 D is produced by granulomatous states (i.e. sarcoidosis), lymphomas, or myobacterium infections, and involves the unregulated production of 1-alpha-hydroxylase enzyme in macrophages. Particle disease is an uncommon condition seen after prosthetic joint replacements and involves the activation of macrophages and subsequent inflammation caused by the local release of microscopic prosthetic fragments. To our knowledge, this is only the second published case in literature of hypercalcemia caused by particle disease.

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