(11.09) Severe, Symptomatic Hypercalcemia Secondary to PTH-Secreting Pancreatoblastoma

Hypercalcemia is a clinical syndrome seen in approximately 1% of the general population. Most cases of hypercalcemia can be attributed to either primary hyperparathyroidism or hypercalcemia of malignancy. Non-parathyroid tumors with ectopic parathyroid hormone (PTH) production are an extremely rare cause of PTH dependent hypercalcemia. We report the first case to our knowledge of a patient presenting with severe hypercalcemia caused by an ectopic PTH producing pancreatoblastoma.

Case(s) Description :

A 22-year-old male with a family history of familial adenomatous polyposis (FAP) presented to the emergency department with upper extremity muscular twitching found to have an elevated serum calcium of 15.4 mg/dL (nl: 8.4 – 10.2 mg/dL) and an elevated intact parathyroid hormone to 463 pg/mL (nl: 22.4 – 88.2 pg/mL). Other pertinent laboratory values obtained included 25-OH Vitamin D 14.6 ng/mL (nl: 30.0 – 90.0 ng/mL), 1,25-dihydroxy Vitamin D 112.0 pg/mL (nl: 19.9 – 79.3 pg/mL), and PTH-related protein 10 pg/mL (nl: < 20 pg/mL). He was treated with aggressive IV fluid replacement and zolendronic acid 4mg. He was discharged following symptomatic improvement and normalization of calcium.

Outpatient sestamibi scan and CT neck/larynx did not show aberrant parathyroid pathology.  His serum calcium uptrended again and the patient was started on cinacalcet 30 mg daily. Due to refractory hypercalcemia, the patient underwent bilateral neck exploration with two parathyroid gland excision to no benefit. Post-operatively, the patient developed acute abdominal pain. A CT of the abdomen/pelvis demonstrated a 16cm left retroperitoneal necrotic mass inseparable from the pancreatic body and tail. Endoscopic ultrasound with fine needle aspiration of the mass revealed a pancreatoblastoma.

PET-FDG scan showed uptake by the primary lesion without metastatic disease.

Patient underwent a colonoscopy for pre-operative purposes which demonstrated findings consistent with FAP.

He underwent subtotal distal pancreatectomy. Surgical pathology confirmed pancreatoblastoma of the distal pancreas with focal lymphovascular invasion.

Intra-operative PTH declined from 843.5 pg/mL to 42.7 pg/mL 60 minutes after mass removal.

His post-operative course was complicated by hypocalcemia and hypoparathyroidism which improved with exogenous calcium and calcitriol replacement, eventually achieving normal serum calcium and PTH levels as an outpatient.

Two months following discharge, repeat CT abdomen/pelvis demonstrated a new 1.7cm right hepatic lobe lesion concerning for metastasis. He has established care with an oncologist with plans for adjuvant chemotherapy.

Discussion :

Ectopic PTH secreting neoplasms represent an extremely rare cause of PTH-dependent hypercalcemia. Our patient represents the first documented case of a PTH secreting pancreatoblastoma. Pancreatoblastomas are rare pancreatic tumors with paraneoplastic potential that have been associated with FAP. Providers should maintain non-parathyroid sources of PTH production in the differential for PTH dependent hypercalcemia.