Treatment-Resistant Hypercalcemia Secondary to Ectopic PTH Hypersecretion From Disseminated Ovarian Cancer

Abstract

Background: Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH from a disseminated mucinous ovarian adenocarcinoma. Case Presentation: A 45-year-old female presented with confusion, constipation, fatigue, and abdominal pain two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with metastasis to the bladder, parametrium, vagina, right ovary, and rectosigmoid. Subsequent CT revealed numerous bilateral pulmonary nodules, hilar adenopathy, liver lesions, and abdominal adenopathy. On exam, she was tachycardic and hypertensive with diaphoresis, dry mucous membranes, respiratory distress, guarded abdominal tenderness, and altered mental status. Her labs were significant for a serum calcium of 21.7 mg/dL, creatinine of 1.93 mg/dL, ferritin of 2,379 ng/mL, leukocytosis of 21.9 bil/L, PTH of 1,061 pg/mL, and PTHrP of 29 pmol/L. Ectopic PTH secretion was highly suspected after negative parathyroid ultrasound. Pamidronate (60 mg IV), calcitonin (200 U IM), and fluid resuscitation were unable to normalize her serum calcium, resulting in the need for dialysis and subsequent continuous renal replacement therapy. Further intervention with denosumab (120 mg SQ), etelcalcetide (5 mg IV), and cinacalcet (60 mg PO) was also attempted. Serum calcium began to decline, but repeat PTH resulted greater than 2,500 pg/mL. Unfortunately, the patient died just one week into her hospital course from septic shock and multi-organ system failure. Discussion: Hypercalcemia of malignancy typically arises from tumor secretion of PTHrP, cytokine release from osteolytic metastases, or tumor production of calcitriol. In cases of hypercalcemia due to excess PTH secretion, primary parathyroid etiologies are typically considered while ectopic PTH-secreting tumors are rare. PTH staining of biopsy specimens and total body sestamibi scan may prove useful in the early detection and treatment of these tumors, but HCM offers a poor prognosis with mean survival of 2 to 3 months and in-hospital mortality of 6.8%. Currently, there are only three cases in the reported literature of ectopic PTH-induced hypercalcemia related to ovarian cancer. To our knowledge, this is the fourth reported case. Conclusion: Ectopic PTH-secreting tumors carry a poor prognosis and should be considered in cancer patients presenting with PTH-associated hypercalcemia. Biopsy staining for PTH and total body sestamibi scan may assist in the early detection of these tumors, but current treatment strategies offer suboptimal outcomes.