An Unusual Case of Hypercalcemia Due to Graft Versus Host Disease

GVHD (Graft-vs-host disease) is the leading cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. We describe an unusual case of hypercalcemia due to GVHD.

Case Description:

A 67-year-old female with myelodysplastic syndrome who underwent an allogeneic stem cell transplant in September 2019 presented to the Bone Marrow Transplant clinic in September 2020 with dysphagia, generalized muscle aches, and nausea for 2 weeks. Her medications included cholecalciferol 2000 units daily. Examination showed normal vitals and rash. Labs showed serum calcium 14.3 mg/dL (normal 8.5 – 10.6), corrected calcium 14.9 mg/dl, Ionized calcium 1.91 mmol/L (1.0 – 3), CPK 316 U/L (21- 215), Albumin 3.3 g/dl, ALP 176 U/L, AST 97 U/L, ALT 37 U/L and Creatinine 1.6 mg/dL. Her PTH was 4.2 pg/ml (10-65), PTHrp < 0.4 pmol/L (normal < = 4.2), TSH 0.47 mcu/ml (0.35 – 5.00), Vitamin D 43.4 ng/ml (30 – 80). She had elevated 1, 25 Vitamin D at 102.0 pg/ml (normal range 19.9 – 79.3 pg/ml). Chest X-ray was normal and did not show abnormal lymphadenopathy. She was diagnosed with Chronic GVHD due to myalgia and elevated CPK. She was started on iv fluid hydration and prednisone 60 mg daily. She received Calcitonin 200 units every 12 hours for 2 days. She received one dose of Zoledronic acid 4 mg. 1,25 Vitamin D improved to 28 pg/ml in a month after initiation of steroids and corrected calcium normalized to 8.9 mg/dl. She was discharged on prednisone 60 mg which was tapered slowly as an outpatient over a period of 8 months. She has been off steroids since May 2021 with no recurrence of symptoms and normal calcium between 9.4 – 9.9 mg/dl after discontinuation of prednisone.

Discussion:

Hypercalcemia can present with nonspecific symptoms although it can be a life-threatening metabolic emergency. Hypercalcemia in malignancy can arise due to localized bony destruction by cancer cells, altered osteoclastic activity under the influence of factors secreted by the cancer cells, or due to increased 1,25 dihydroxy vitamin D, parathormone (PTH), or parathyroid hormone-related protein (PTHrP). Hypercalcemia due to the calcitriol-mediated process is seen in Hodgkin’s and Non-Hodgkins Lymphoma. In calcitriol-mediated hypercalcemia, there is enhanced osteoclastic bone resorption and excessive gastrointestinal calcium absorption. Association between GVHD in post-BMT transplant and calcitriol-mediated hypercalcemia has not been widely reported. As our patient did not have any other apparent etiology for elevated 1,25 Vitamin D other than GVHD, a likely diagnosis of GVHD causing hypercalcemia due to elevated 1,25 Vitamin D was made and treated successfully with steroid therapy.