From the Guidelines
After detecting elevated parathyroid hormone-related protein (PTHrP) in an older woman with hypercalcemia, the most important tests to order include a comprehensive malignancy workup, starting with chest, abdomen, and pelvis CT scans with contrast, as PTHrP-mediated hypercalcemia is strongly associated with malignancy, particularly lung, breast, renal, and gynecological cancers 1. This approach is crucial because the presence of elevated PTHrP in the context of hypercalcemia in an elderly patient strongly suggests humoral hypercalcemia of malignancy, which necessitates the prompt identification of the underlying cancer for appropriate management.
Key Tests for Malignancy Workup
- Chest, abdomen, and pelvis CT scans with contrast to identify potential primary tumors
- Mammography and breast ultrasound, given the high incidence of breast cancer in older women
- Complete blood count, comprehensive metabolic panel, serum protein electrophoresis, and urine protein electrophoresis to assess for multiple myeloma
- Bone scan or skeletal survey to identify bone metastases
- Specific tumor markers like CEA, CA 15-3, CA 125, and PSA, based on clinical suspicion
- Consideration of a PET-CT scan if initial imaging is negative but malignancy suspicion remains high
Importance of Accurate PTH Measurement
While the provided evidence discusses the importance of accurate PTH measurement in various contexts, including primary and secondary hyperparathyroidism 1, the immediate concern in this scenario is the potential for malignancy. Thus, the focus should be on a comprehensive malignancy workup rather than the nuances of PTH assay generations.
Treatment of Hypercalcemia
While pursuing the diagnostic workup, it is essential to initiate treatment of hypercalcemia with IV fluids, bisphosphonates (such as zoledronic acid 4mg IV), and possibly calcitonin (4 IU/kg SC every 12 hours) for severe cases, as hypercalcemia can lead to significant morbidity and mortality if not promptly addressed.
The approach outlined above prioritizes the identification and management of potential malignancy, which is critical for improving outcomes in terms of morbidity, mortality, and quality of life for the patient.
From the Research
Diagnostic Approach
After detecting an elevated PTHrP in an older lady with hypercalcemia, the following tests should be ordered:
- Intact parathyroid hormone (PTH) levels to distinguish between PTH-dependent and PTH-independent causes of hypercalcemia 2
- N-terminal PTHrP assay, as C-terminal PTHrP levels can be elevated in patients with chronic kidney disease (CKD) without malignancy 3
- Serum calcium, phosphate, and vitamin D levels to assess the severity of hypercalcemia and guide further management 2, 4
- Renal function tests, such as creatinine and urea, to evaluate kidney function and potential CKD 3
- Imaging studies, such as chest X-ray, CT scan, or bone scan, to investigate potential malignancies or other causes of hypercalcemia 5
Considerations
- A PTH cutoff of >26 ng/l can predict a non-increased PTHrP result, making PTHrP testing less informative in such cases 6
- The clinical presentation and severity of hypercalcemia should guide the urgency and aggressiveness of the diagnostic workup and treatment 2, 4
- The prognosis and survival of patients with PTHrP-mediated hypercalcemia vary depending on the underlying cause, with solid organ malignancies having the shortest survival 5