Neuroendocrine Tumor Associated Severe Hypercalcemia of Pregnancy

Background: Literature of pregnancy associated neuroendocrine tumors is limited. We report an unusual case of severe hypercalcemia of pregnancy secondary to a neuroendocrine tumor. Clinical Case: A 43-year-old lady presented to our center in her 28(th) week of pregnancy with complaints of worsening nausea and epigastric pain over few days. She had developed gestational diabetes at 24 weeks for which she was taking insulin. On examination she was tachycardic, mildly confused with a distended abdomen. Serum chemistries revealed serum calcium of 15.9 mg/dL, elevated PTHrP of 64 pg/mL and low PTH of 2 pg/mL consistent with PTHrP mediated hypercalcemia. She had low 25-OH- vitamin D (15 ng/mL) with normal 1–25- OH vitamin D. An abdominal ultrasound showed a solid, heterogenous, soft tissue mass interposed between the left kidney and spleen measuring 11 x 9 x 12 cm. This was confirmed on Abdominal MRI, which also showed multiple large hepatic metastasis. Tumor biopsy with pathology confirmed well differentiated neuroendocrine tumor of gastric or pancreatic origin. Her hypercalcemia was initially treated with infusions of IV normal saline, furosemide diuresis, calcitonin 200 units SC 12 hourly and a single dose of dexamethasone 10 mg IV. Calcitonin and diuresis were discontinued after 5 days once calcium improved to 10 mg/dL. Oncology deferred treatment of the tumor until she had delivered. Patient was discharged with serum calcium of 10.7 mg/dL and counselled for plenty of oral hydration. She was readmitted with nausea, vomiting and serum calcium level of 15.1 mg/dL at 32 weeks gestation. She was again treated with a similar regimen of IV saline and furosemide along with calcitonin 480 units SC 12 hourly and prednisone 10 mg daily, but calcium levels remained high (13.6 mg/dL) despite aggressive treatment. Labor was induced at 33 weeks and she delivered a healthy boy through an uncomplicated vaginal delivery. Remarkably, her serum calcium normalized on day two post-partum and remained so throughout. Her serum calcium remains normal at 2 months post-partum (10.3 mg/dL, PTHrP 36 pg/mL, PTH 7 pg/mL) despite the presence of unresected tumor. She is planned to undergo surgical resection of the tumor and hepatic metastatic lesions. Conclusion: Clinicians must be aware that severe hypercalcemia may be the presenting manifestation of neuroendocrine tumors in pregnancy. In this case, we hypothesize a potential placental contribution to her elevated PThrP given resolution of hypercalcemia post-delivery. However, persistent elevated PThrP post-partum may also be physiologic or related to the abdominal tumor. A placental histopathological could be performed due to logistic reasons.