A 68‐year‐old woman presented to the ER with 3 weeks of increased forgetfulness, confusion, headache, unsteady gait, and abdominal pain. Her medical history was significant for hypertension, depression, breast cancer, and endometrial cancer (the latter 2 both surgically resected). Current medications included losartan, escitalopram, lorazepam, pantoprazole, and up to 3 g of calcium supplements daily. Physical examination revealed decreased comprehension, tangential thought process, abdominal discomfort, left‐sided dysmetria, and unstable posture with a narrow gait. Initial concern was for a stroke, and an emergent MRI was normal. Closer scrutiny of lab values showed elevated calcium (17.5 mg/dL), Cr (1.14 mg/dL), and HCO3− (31 mm/L), normal phosphate, and a protein gap of 3.2. The patient was aggressively hydrated and administered pamidronate. Calcium levels improved and remained stable at 8–9 mg/dL over the hospital course. All her symptoms completely resolved. Further workup revealed a low intact PTH, normal PTHrP, low 25(OH)D3, and an elevated 1,25(OH)2D3. SPEP and UPEP were normal. Chest x‐ray showed no granulomatous disease, and whol‐body bone scan showed no evidence of osteolytic lesions. A CT scan showed extensive lymphadenopathy with a splenic lesion that raised suspicion for lymphoma. Following diagnostic laparoscopy with pathological examination of a splenic mass biopsy, the patient was diagnosed with stage IIIA diffuse large B‐cell lymphoma.
Hypercalcemia is a relatively common complication of lymphoma, and increased levels of the active vitamin D metabolite 1,25(OH)2D3 are seen with lymphoma. There was suspicion for milk alkali syndrome due to excess calcium intake with mild renal dysfunction and metabolic alkalosis, but this is usually associated with >4–5 g calcium daily and low/normal active vitamin D levels. In the presence of suppressed PTH, our patient's elevated 1,25(OH)2D3 level is consistent with an extrarenal source of 1,25(OH)2D3. It has been proposed that lymphoma‐associated macrophages harbor the ectopic, PTH‐independent 1α‐hydroxylase activity, which converts the inactive precursor 25(OH)D3 to 1,25(OH)2D3. The excessive 1,25(OH)2D3 concentration indicates a lack of negative feedback regulation on this extrarenal 1α‐hydroxylase. Though our patient had low 25(OH)D3 levels, 1,25(OH)2D3 synthesis is usually not limited by 25(OH)D3 levels. Corticosteroids are the most effective calcium‐lowering treatment for hypercalcemia due to elevated 1,25(OH)2D3. In addition, the patient's levels normalized following initial bisphosphonate administration. This exemplifies the finding that patients with lower PTHrP levels generally respond well to bisphosphonates.
The patient's stroke‐like presentation was also typical of symptoms related to hypercalcemia. Further investigation diagnosed an underlying malignancy, showing the importance of paying close attention to routine labs.
To cite this abstract:Dibble S, Ansari A. Hypercalcemia: Showing a Path from Stroke to Cancer. Abstract published at Hospital Medicine 2013, May 16-19, National Harbor, Md. Abstract 313. Journal of Hospital Medicine. 2013; 8 (suppl 2). https://www.shmabstracts.com/abstract/hypercalcemia-showing-a-path-from-stroke-to-cancer/. Accessed March 29, 2020.