Abstract: PO0363
Hypercalcemia Resulting from Spindle Cell Tumor-Induced Calcitriol Production
Session Information
- Biochemical Aspects of Mineral and Bone Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Gopal, Tejas, University of Texas at Austin, Austin, Texas, United States
- Neelam, Pranu, University of Texas at Austin, Austin, Texas, United States
- Nader, Paul C., University of Texas at Austin, Austin, Texas, United States
Introduction
Less than 1% of cases of hypercalcemia of malignancy are caused by overproduction and release of 1,25-dihydroxy vitamin D (calcitriol) by tumor cells.1 Calcitriol excess has been identified most often in sarcoidosis, hematologic malignancy, and infection.2 We present a patient who developed severe hypercalcemia and acute kidney injury as a result of spindle cell neoplasm-mediated calcitriol excess, with normalization of serum calcium and creatinine in response to treatment with prednisone.
Case Description
A 65yo man with a history of a large retroperitoneal mass presented with malaise. He was not taking calcium or vitamin D supplements. Initial lab showed serum calcium 15.7 mg/dL, 1,25-dihydroxy Vit. D 126 pg/mL (elevated), and creatinine 4.5 mg/dL. His PTH 8 pg/mL, PTHrP 0.8 pmol/L, and 25-hydroxy Vit. D 26 ng/mL were suppressed or normal. SPEP, UPEP, serum immunofixation, and serum free light chains were unremarkable. Pathology of the mass revealed a spindle cell neoplasm embedded within fibrous stroma. Prednisone was prescribed to suppress tumor-associated calcitriol production. His serum calcitriol level fell to 33.2 pg/mL, with a serum calcium of 10.9 mg/dL, after taking prednisone 40 mg/day for 2 weeks. His calcitriol 39.2 pg/mL, calcium 8.7 mg/dL, and creatinine 0.81 mg/dL levels were normal while on prednisone 20 mg/day at 76 days after starting corticosteroids and before any anti-tumor therapy or surgical debulking.
Discussion
The conversion of 25-hydroxy Vit. D to calcitriol is catalyzed by 1-alpha hydroxylase, a phenomenon that can occur in extra-renal tissues, such as within macrophages in sarcoid tissue.3-6 We hypothesize that elevated 1-alpha hydroxylase activity in spindle tumor cells or in activated macrophages within tumor stroma was responsible for excess calcitriol production and the resultant hypercalcemia. Corticosteroids inhibit the 1-alpha hydroxylase conversion of 25-hydroxy Vit. D to calcitriol and have been used successfully to reduce malignancy-induced calcitriol production.6,7 This case provides evidence of severe hypercalcemia due to endogenous production of calcitriol associated with a large spindle cell neoplasm, with rapid normalization of both serum calcium and calcitriol levels in response to treatment with prednisone, without anti-tumor therapy or surgical debulking.