Hypercalcemic Crisis Due to PTH Secretion from a Poorly Differentiated Esophageal Neuroendocrine Tumor

Document Type

Article

Abstract

Background: Paraneoplastic secretion of PTH is described in a number of solid organ tumors. Hypercalcemia occurs in up to 30% of patients with malignancy. The most common cause of this phenomenon is PTHrP production. We present a rare case of PTH mediated hypercalcemic crisis from a tumor of presumed esophageal lineage.

Clinical Case: A 54-year-old man presented with several days of fatigue, lethargy and polyuria. Initial calcium was markedly elevated at 18.4 (8.3-10.1mg/dL). Past medical history included Barrett's esophagus, history of gastric bypass, and prior alcohol abuse. He also had progressive dysphagia and 30lb weight loss over the prior month. On examination, he had tachycardia, cachexia, and encephalopathy. Laboratory testing revealed an elevated PTH of 281 (nl 18.4-80.1pg/mL), creatinine 1.34mg/dL, and low phosphorus at 2.8 (nl 2.7-4.5mg/mL). Hypercalcemia was treated with IV fluids, calcitonin, and pamidronate. The calcium normalized but PTH remained 210pg/mL. Subsequent PTHrP and 1,25 di-hydroxy vitamin D levels were normal. Esophagogastroduodenoscopy (EGD) revealed a friable esophageal mass and biopsy identified a poorly differentiated carcinoma with neuroendocrine features, immunoreactive to synaptophysin and high Ki-67 index of 90%. Immunostains for chromogranin and PTH were negative. A CT of the chest, abdomen, and pelvis revealed diffuse metastases in the liver, lungs, and enlarged mediastinal lymph nodes. The source of primary tumor could not be fully identified from pathology but suspected to be esophageal. Parathyroid scan showed a subtle persistent uptake posterior to right side of trachea suspicious for a parathyroid adenoma, but that could not account for the severity of PTH elevation. He was readmitted in 1 month with recurrent symptomatic severe hypercalcemia to 18mg/dL and PTH to 619.4pg/mL. Again, he received IV fluids, calcitonin, and zoledronic acid. He received 3 cycles of platinum and etoposide based chemotherapy. After chemotherapy, PTH decreased to 123pg/mL and calcium to 9.7mg/dL but he continued to have rapid disease progression including jaundice, pathological bone fractures and orbital metastases. He elected hospice care and passed away in about 4 months from initial diagnosis. Final PTH was 916.8pg/mL.

Conclusion: PTH is a normally secreted by parathyroid gland chief cells, which are part of the embryonic neural crest cells found in various neuroendocrine tissues. It is plausible that malignancies with neuroendocrine features may secrete neuropeptides including PTHrP and PTH. Few case reports exist describing PTH secretion by neuroendocrine tumors, though most common are tumors of gastroenteropancreatic origin. PTH stain and focal chromogranin tends to be negative with poorly differentiated neuroendocrine tumors. PTH gene is usually intact and upregulation of the regulator sequence of PTH gene promotor is suspected to be the mechanism of elevated PTH levels and hypercalcemia. This case demonstrates the potential for poorly differentiated neuroendocrine malignancies to cause hypercalcemic crises from paraneoplastic secretion of PTH.

First Page

A872

Last Page

A873

DOI

10.1210/jendso/bvac150.1805

Publication Date

11-1-2022

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