Isolated nonparathyroid hormone-mediated hypercalcemia: a rare presentation of retroperitoneal sarcoidosis.

Non-parathyroid hormone (PTH)-mediated hypercalcemia has diverse etiologies, including granulomatous disorders such as sarcoidosis, in which extrarenal 1-α-hydroxylase activity leads to excess production of 1,25-dihydroxyvitamin D (1,25(OH)₂D). We report a rare case of sarcoidosis presenting as isolated hypercalcemia without pulmonary involvement, complicated by initially normal 1,25(OH)₂D levels and a false-negative core biopsy. A 44-year-old man with hypertension and type 2 diabetes presented with malaise, polyuria, and polydipsia. Laboratory evaluation showed severe hypercalcemia with suppressed PTH. PTH-related peptide, 25-hydroxyvitamin D, TSH, and albumin were normal. Imaging revealed no osseous lesions or lymphadenopathy. He improved with intravenous fluids, calcitonin, and zoledronic acid. Three months later, he re-presented with recurrent hypercalcemia and elevated 24-hour urinary calcium excretion. Outpatient evaluation revealed elevated 1,25(OH)₂D and retroperitoneal lymphadenopathy. Core needle biopsy was nondiagnostic, but subsequent excisional biopsies of retroperitoneal lymph node confirmed nonnecrotizing granulomatous inflammation. He was diagnosed with sarcoidosis and started on high-dose steroids, later transitioning to mycophenolate. With that treatment, calcium levels normalized quickly. This case highlights the diagnostic complexities of non-PTH-mediated hypercalcemia and underscores the importance of a comprehensive workup, including medication review, laboratory tests, radiography, and biopsy, with consideration for excisional biopsy.