RF30 | PSAT135 Rare Case of Hypercalcemia Mediated by an Ectopic Parathyroid Hormone (PTH), and Parathyroid Hormone-Related Peptide (PTHrP) Co-Secretion Secondary to Metastatic Cervical Carcinoma
Authors: Gaballa Salem , Khosla Shikha , Naser Nejat 
Published: November 2022

Abstract

Introduction
Hypercalcemia of malignancy occurs in ∼20-30% of cancer patients. This mostly occurs by three mechanisms: humoral mediated from excess production of PTHrP, osteoclast mediated bone resorption from osteolytic metastasis and calcitriol mediated in granulomatous diseases such as lymphoma. Very rarely, PTH mediated hypercalcemia can occur in the setting of ectopic PTH production from tumor cells.

Case presentation
A 57 year- old woman with a medical history of hypertension and hyperthyroidism presented to the emergency department with several days of fatigue, nausea, vomiting, constipation and abdominal pain. Exam was remarkable for a heart rate (HR) of 140, lethargy, dry mucous membranes and chronic bilateral proptosis. Labs were remarkable for corrected calcium level of 18.38 mg/dl, Phosphorous of 3.2 mg/dL, Mg level of 1.2 mEq/L, blood urea nitrogen (BUN) of 20 mg/dL, creatinine of 1.6 mg/dL alkaline phosphatase of 170 units/L, and Lactic acid was 3.0 mmol/L. TSH 0.291 (0.40-4.7), FT4 1.51 ng/dl (0.70-1.80), FT3 3.2 pg/ml (2.8-5.3). Patient was treated with IV fluids, calcitonin 4u/kg bid, zoledronic acid 4 mg and started on cinacalcet. Further workup revealed elevated PTH of 1351 pg/ml (16-80), PTH-rP of 28 (&lt;2), 25-hydroxyvitamin D of 25.5 ng/ml (30-100), 1,25-dihydroxy vitamin D level of 59.8 pg/ml (19.9-79.3). Patient couldn't tolerate sestamibi scan. 4DCT couldn't be performed due to creatinine elevation Bedside US performed did not show any evidence of parathyroid adenoma. CT, abdomen and pelvis a large mass in the cervix and cecum. Cervical biopsy revealed necrotic tumor with vary rare nests of viable atypical cells. Given persistent hypercalcemia, despite additional treatment, CRRT was initiated on hospital day 15 with rapid normalization of calcium level. However, patient continued to rapidly deteriorate with multi-organ failure and was transitioned to comfort care before expiring. Autopsy revealed poorly differentiated necrotic cervical carcinoma measuring 12×6×8 cm with metastasis to the left ovary as well as multiple tumor lesions in the liver. Parathyroid glands were normal on gross exam. PTH staining could not be performed given degree of tumor necrosis

Discussion
Hypercalcemia with elevated PTH and negative localization studies, should raise suspicion for ectopic PTH production from underlying malignancy. In PTHrP mediated hypercalcemia, PTH as well as 1,25 (OH) D are expected to be suppressed. This patient had an elevated PTHrP but not enough to suppress PTH or 1,25 (OH) D level. Given that parathyroid glands were normal on gross exam; this is consistent with ectopic PTH mediated hypercalcemia with component of PTHrP co-secretion. Hypercalcemia of malignancy presents late and portends a poor prognosis and therefore appropriate diagnosis and management is critical.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.