Case Reports

Hypercalcemia Is of Uncertain Significance in Patients With Advanced Adenocarcinoma of the Prostate

Hypercalcemia in the setting of prostate cancer is rare with an uncertain pathophysiology and more research is needed into the role of parathyroid hormone-related peptide as a growth factor and possibly target-directed monoclonal antibody therapies.

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Hypercalcemia is found when the corrected serum calcium level is > 10.5 mg/dL. 1 Its symptoms are not specific and may include polyuria, dehydration, polydipsia, anorexia, nausea and/or vomiting, constipation, and other central nervous system manifestations, including confusion, delirium, cognitive impairment, muscle weakness, psychotic symptoms, and even coma. 1,2

Hypercalcemia has varied etiologies; however, malignancy-induced hypercalcemia is one of the most common causes. In the US, the most common causes of malignancy-induced hypercalcemia are primary tumors of the lung or breast, multiple myeloma (MM), squamous cell carcinoma of the head or neck, renal cancer, and ovarian cancer. 1

Men with prostate cancer and bone metastasis have relatively worse prognosis than do patient with no metastasis. 3 In a recent meta-analysis of patients with bone-involved castration-resistant prostate cancer, the median survival was 21 months. 3

Hypercalcemia is a rare manifestation of prostate cancer. In a retrospective study conducted between 2009 and 2013 using the Oncology Services Comprehensive Electronic Records (OSCER) warehouse of electronic health records (EHR), the rates of malignancy-induced hypercalcemia were the lowest among patients with prostate cancer, ranging from 1.4 to 2.1%. 1

We present this case to discuss different pathophysiologic mechanisms leading to hypercalcemia in a patient with prostate cancer with bone metastasis and to study the role of humoral and growth factors in the pathogenesis of the disease.

Case Presentation

An African American man aged 69 years presented to the emergency department (ED) with generalized weakness, fatigue, and lower extremities muscle weakness. He reported a 40-lb weight loss over the past 3 months, intermittent lower back pain, and a 50 pack-year smoking history. A physical examination suggested clinical signs of dehydration.

Laboratory test results indicated hypercalcemia, macrocytic anemia, and thrombocytopenia: calcium 15.8 mg/dL, serum albumin 4.1 mg/dL, alkaline phosphatase 139 μ/L, blood urea nitrogen 55 mg/dL, creatinine 3.4 mg/dL (baseline 1.4-1.5 mg/dL), hemoglobin 8 g/dL, mean corpuscular volume 99.6 fL, and platelets 100,000/μL. The patient was admitted for hypercalcemia. His intact parathyroid hormone (iPTH) was suppressed at 16 pg/mL, phosphorous was 3.8 mg/dL, parathyroid hormone-related peptide (PTHrP) was < 0.74 pmol/L, vitamin D (25 hydroxy cholecalciferol) was mildly decreased at 17.2 ng/mL, and 1,25 dihydroxy cholecalciferol (calcitriol) was < 5.0 (normal range 20-79.3 pg/mL).

A computed tomography (CT) scan of the chest and abdomen was taken due to the patient’s heavy smoking history, an incidentally detected right lung base nodule on chest X-ray, and hypercalcemia. The CT scan showed multiple right middle lobe lung nodules with and without calcifications and calcified right hilar lymph nodes (Figure 1).

To evaluate the pancytopenia, a bone marrow biopsy was done, which showed that 80 to 90% of the marrow space was replaced by fibrosis and metastatic malignancy. Trilinear hematopoiesis was not seen (Figure 2). The tumor cells were positive for prostate- specific membrane antigen (PSMA) and negative for cytokeratin 7 and 20 (CK7 and CK20). 4 The former is a membrane protein expressed on prostate tissues, including cancer; the latter is a form of protein used to identify adenocarcinoma of unknown primary origin (CK7 usually found in primary/ metastatic lung adenocarcinoma and CK20 usually in primary and some metastatic diseases of colon adenocarcinoma). 5 A prostatic specific antigen (PSA) test was markedly elevated: 335.94 ng/mL (1.46 ng/mL on a previous 2011 test).


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