MON-746 Severe Hypercalcemia In A Patient With Metastatic Colon Cancer: Role of Parathyroid Hormone and Vitamin D

Abstract Disclosure: P.I. Alfonso: None. S. Ramadan: None. Z. He: None. Background: Humoral hypercalcemia of malignancy (HHM), driven by PTHrP, is the most common cause of hypercalcemia in malignancy. Simultaneously elevated PTH is rare. We present here a concurrent hyperparathyroidism and elevated PTHrP in a patient with metastatic colon cancer. Case: A 25-year-old female with Peutz-Jeghers syndrome and metastatic right-sided colon adenocarcinoma presented with symptomatic hypercalcemia (16.8 mg/dL). She was on adagrasib and cetuximab after progression on FOLFIRINOX. Her calcium had acutely risen from 9.0 mg/dL two weeks prior. Labs showed a PTH of 124 pg/mL (<65 pg/mL) and unexpectedly elevated PTHrP of 3.1 pmol/L (<2 pmol/L) in the setting of elevated alkaline phosphatase. CT imaging did not identify obvious osteolytic bone metastases. Hypercalcemia resolved rapidly with IV fluids, calcitonin and zoledronic acid. Persistent hypophosphatemia (0.8 mg/dL), low magnesium (1.8 mg/dL), and vitamin D deficiency (7 ng/mL) were corrected. Neck ultrasound did not identify suspicious parathyroid lesions. Discussion: This case underscores the importance of considering PTH-mediated hypercalcemia in patients with malignancy. Differentiating between primary hyperparathyroidism, ectopic PTH secretion, and malignancy-associated hypercalcemia is critical to guiding treatment strategies.Additionally, vitamin D deficiency remains a significant issue. Current guidelines discourage routine 25(OH)D screening in the general population but do not specifically address cancer patients. This patient highlights the potential impact of unrecognized vitamin D deficiency on calcium homeostasis and secondary hyperparathyroidism, indicating the need for aggressive screening approaches in high-risk individuals. The presence of elevated PTHrP alongside hyperparathyroidism is an intriguing finding. While PTHrP is known to suppress PTH secretion, the reverse remains unclear. Further investigation is needed to determine whether their interaction represents an underrecognized endocrine interaction. Conclusion: This case challenges conventional hypercalcemia workups in patients with malignancy, emphasizing that multiple pathways may contribute simultaneously. While guidelines discourage PTHrP testing once PTH is elevated, exceptions exist. In addition, vitamin D deficiency remains undertreated due to lack of screening, despite potential implications for malignancy-related calcium disorders. Future management should include continued endocrinologic and oncologic evaluation to clarify the hormonal interplay and optimize treatment. Presentation: Monday, July 14, 2025