Case Presentation: The patient is a 27-year-old with past medical history that includes pancreatic tail adenocarcinoma involving the liver, status post multiple treatments and on admission she was status post cycle #2 of gemcitabine, Abraxane. Patient presented to the cancer center with complaints of worsening altered mental status for 2 days accompanied by her mother. Additionally, she has history of deep vein thrombosis, pulmonary embolism (not on anticoagulation due to thrombocytopenia) and status post inferior vena cava filter, and CVA. On admission she was also complaining of acute on chronic cancer-related pain, constipation with no bowel movements for the prior 4 days. Abnormal Lab values were as follows:Calcium corrected to albumin 16.7, normal (8.6 to 10.2), Magnesium 1.5, normal (1.7-22), Thyroid-stimulating hormone 0.614, normal (0.27 – 4.2), Free T3 1.46, normal (2.3-4.1), Phosphorus 1, normal (15-65), Parathyroid hormone 8.5, normal (10-65), Parathyroid hormone Pro peptide 79.2, normal (0.0-3.4). The hypercalcemia was treated with Zometa, calcitonin, and phosphorus replacement. For the Altered Mental status, the patient had CT scan of the brain and neck showing infarct involving the anterior pons with no hemorrhage present and right insular subacute infarct with linear necrosis. Neurology service was consulted with no findings of acute neurological issues explaining her encephalopathy. Her altered mental status was thought to be contributed by the hypercalcemia.
Discussion: Hypercalcemia associated with adenocarcinoma of the pancreas is uncommon and a rare phenomenon. It is rarely reported in literature. Humeral hypercalcemia (HHM) without bone metastasis is a paraneoplastic syndrome that is more often associated with Squamous cell carcinoma of the lung, head and neck. Parathyroid levels are thought to be normally low in these patients, but the parathyroid hormone related peptide (PTHrP) that is produced facilitates hypercalcemia.PTHrP is a protein similar to PTH and therefore has the ability to bind to PTH receptors. Elevated levels have been shown in most patients with HHM. Elevated levels of PTHrP with normal levels of PTH appear to become a hallmark for diagnosis in pancreatic adenocarcinoma associated HHM, and hypercalcemia appears to be the presenting characteristic of the primary tumor and subsequent metastasis.
Conclusions: Hypercalcemia is a rare paraneoplastic manifestation of pancreatic adenocarcinoma, more commonly associated with squamous cell carcinomas. For this patient, suppressed PTH with an elevated PTHrP confirmed HHM. Patients with severe hypercalcemia (>14 mg/dL) can experience lethargy, confusion, coma, anxiety, depression, and cognitive changes. The patient’s history of pulmonary embolism, thrombocytopenia limiting anticoagulation, and advanced malignancy likely contributed to her cerebrovascular event, while hypercalcemia exacerbated encephalopathy. Early recognition and treatment with intravenous fluid hydration, bisphosphonates, calcitonin, and electrolyte correction are hallmark, though prognosis in this setting remains poor. This case shows the importance of considering metabolic derangements such as paraneoplastic hypercalcemia in the differential diagnosis of encephalopathy in patients with cancer. Identifying HHM in pancreatic adenocarcinoma expands the recognized manifestations of this malignancy and highlights the importance of monitoring for metabolic complications in patients with advanced disease.