P0873 - An Unusual Presentation of T-Cell Acute Lymphoblastic Leukemia: Syncope and Hypercalcemia of Malignancy

Introduction:

Hypercalcemia is an exceedingly rare presentation of T-cell acute lymphoblastic leukemia (ALL) in children. While often varied and nonspecific, the clinical manifestations of hypercalcemia can provide a clue to severe underlying disease, making prompt diagnosis imperative.

Case Description:

A previously healthy 14-year-old girl presented to the emergency department after multiple witnessed syncopal episodes. The events were preceded by dizziness and lasted approximately 10-15 seconds. She had no associated abnormal movements, incontinence, or subsequent confusion. Review of systems revealed one episode of emesis; left rib pain, polyuria, and polydipsia for 1-2 months. She denied recent illnesses, inciting stressors, substance abuse, dieting, and supplement or medication use. Her family history was significant for maternal hypothyroidism and kidney stones.

Her physical examination was unremarkable. Her chemistry revealed a serum calcium of 15 mg/dL and acute kidney injury with blood urea nitrogen of 26 mg/dL and creatinine 1.49 mg/dL. Alkaline phosphatase was elevated to 185 U/L and albumin was normal. Complete blood count was normal except a platelet count of 114,000/µL. D-dimer and erythrocyte sedimentation rate were elevated. Electrocardiogram, computed tomography brain, chest radiograph, urinalysis and urine toxicology were unremarkable. Renal ultrasound revealed bilaterally enlarged kidneys without nephrocalcinosis, making chronic hypercalcemia unlikely. She was admitted for further work-up and started on 200ml/hr normal saline fluids and calcitonin.

Her parathyroid hormone (PTH) was suppressed, thus work-up for non-PTH mediated causes was pursued. She had a low 1,25-(OH)2 vitamin D and normal 25-OH vitamin D, ruling out ectopic activation of 1-alpha hydroxylase and vitamin D intoxication. Free T4, thyroid stimulating hormone, and morning cortisol were normal, ruling out other endocrinologic pathologies. Peripheral smear revealed 2-5% leukemic blasts and bone marrow biopsy confirmed T-cell ALL diagnosis and hypercalcemia of malignancy (HCM). Her PTH-related peptide (PTH-rp) level was normal.

Discussion:
T-cell ALL commonly presents with fever, lethargy, bleeding, lymphadenopathy, mediastinal mass, and blood cell count derangements. HCM occurs in less than 1% of cases of childhood ALL. HCM is secondary to tumor PTHrp production in 80% of cases, with tumor PTH or 1,25-(OH)2 vitamin D production being more rare mechanisms. However, low levels of these markers do not exclude HCM. Osteolysis caused by tumor cytokine release accounts for 20% of HCM cases. HCM is often severe and acute in onset, thus manifests with more symptoms than other causes of hypercalcemia. Patient presentation is often nonspecific and can include abdominal pain, nausea, vomiting, constipation, seizures, lethargy, and EKG abnormalities. Hypercalcemia can induce nephrogenic diabetes insipidus, leading to polyuria, hypovolemia, and acute kidney injury. Severe hypercalcemia is treated with IV fluids and calcitonin, as well as bisphosphonates in refractory cases.

Conclusion: Pediatricians should be aware that hypercalcemia of malignancy is a rare but potentially life-threatening presentation of T-cell ALL.