SAT-347 Diagnosis of Autosomal Dominant Hypocalcemia Type 1 Following the Initiation of Imatinib for Treatment of Chronic Myeloid Leukemia

Background: Autosomal Dominant Hypocalcemia Type 1 is an underdiagnosed condition due to the vast majority of patients being asymptomatic and having mild hypocalcemia. Imatinib has been associated with hypophosphatemia and hypocalcemia. Clinical Case: 69-year-old man who had a long history of asymptomatic mild hypocalcemia, calcium level of 7.9 mg/dL (8.4 – 10.2 mg/dL) diagnosed with chronic myeloid leukemia and developed symptoms of hypocalcemia within 2 months of treatment with imatinib. After the initiation of imatinib, his calcium reduced to 6.8 mg/dL (8.4 – 10.2 mg/dL) with a corresponding ionized calcium of 0.98 mmol/L (1.12–1.32 mmol/L) within 2 months. He developed tetany. With the reduced calcium level his PTH was unexpectedly low-normal at 34 pg/mL (16–62 pg/mL). He also had a higher than expected urinary calcium of 342 mg/24 hours. The PTH and 24-hour urinary calcium levels raised concern for an underlying diagnosis of autosomal dominant hypocalcemia type 1. His phosphorous was normal at 3.3 mg/dL (2.6–4.9 mg/dL). He never had hypophosphatemia, which is common with imatinib. After two doses of IV calcium and initiation of oral calcium replacement, 1000 mg BID, his level continued to be reduced with symptoms. Given his symptoms, laboratory results, and continued hypocalcemia he underwent genetic testing. Results of his genetic testing showed a p.Thr151Met mutation in the CASR gene consistent with autosomal dominant hypocalcemia type 1. With this diagnosis, there is concern for nephrolithiasis with over treatment. His symptoms resolved with treatment with calcium 1000mg TID, calcitriol 0.25 mg BID and vitamin D3 2000 IU daily. He has not developed nephrolithiasis and his urinary calcium increased to 424mg/24 hours. A thiazide diuretic is being considered to decrease urinary calcium excretion. He continues on imatinib with an excellent response to therapy. It is likely that the trigger for symptomatic severe hypocalcemia was initiation of imatinib superimposed on the hypocalcemia type 1. Possible mechanisms for this are decreased intestinal absorption, increased urinary loss, or decreased dissolution from bone. (1) These mechanisms are also associated with hypophosphatemia, which our patient did not have. Another possible cause could be an immune mediated destruction of the parathyroid gland, a rare finding seen with other tyrosine kinase inhibitors.(2) Conclusion: This is the first reported case of imatinib triggering severe symptomatic hypocalcemia leading to the diagnosis of underlying autosomal dominant hypocalcemia type 1. References: 1. Vandyke, Kate, et al. “Dysregulation of Bone Remodeling by Imatinib Mesylate.” Blood, vol. 115, no. 4, 2010, pp. 766–774., doi:10.1182/blood-2009-08-237404. 2. Petrić, Marija, et al. “A Rare Case of Hypocalcemia Induced by Nilotinib.” Endocrine Oncology and Metabolism, 3 Mar. 2017, pp. 32–53., doi:10.21040/eom/2017.3.5.1.