From the Guidelines
Elevated PTHrP is a significant clinical finding that typically indicates malignancy-associated hypercalcemia, requiring urgent evaluation and treatment. The clinical significance of elevated PTHrP levels is closely associated with hypercalcemia of malignancy, which occurs in 10% to 25% of patients with lung cancer, as noted in the American College of Chest Physicians evidence-based clinical practice guidelines 1.
Key Considerations
- Hypercalcemia of malignancy is most commonly seen in patients with squamous cell lung cancer.
- The median survival after discovery of hypercalcemia of malignancy in patients with lung cancer is about 1 month, highlighting the need for prompt diagnosis and treatment 1.
- Clinical symptoms of hypercalcemia depend on severity and acuity of onset, ranging from mild symptoms like polyuria and polydipsia to severe symptoms including mental status changes, bradycardia, and hypotension.
Diagnostic Evaluation
- The diagnostic evaluation includes measuring serum concentrations of iPTH, PTHrP, 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, calcium, albumin, magnesium, and phosphorus.
- Comprehensive imaging studies such as CT scans of the chest, abdomen, and pelvis, along with tumor marker testing, are crucial for identifying the underlying malignancy.
Management
- Treatment involves addressing both the hypercalcemia and the underlying malignancy.
- For hypercalcemia management, intravenous fluids (normal saline) should be initiated promptly, followed by bisphosphonates like zoledronic acid if hypercalcemia is severe, as these are usually effective in managing hypercalcemia of malignancy 1.
- Additional therapeutic options such as glucocorticoids, gallium nitrate, and salmon calcitonin may be considered for further management.
From the Research
Elevated PTHrP Significance
Elevated Parathyroid Hormone-related Protein (PTHrP) levels are often associated with hypercalcemia, particularly in patients with malignancy. The significance of elevated PTHrP levels can be understood through the following points:
- Elevated PTHrP levels are a useful prognostic factor in malignancy-associated hypercalcemia, at least in patients aged 65 years or less 2.
- Higher pretreatment calcium levels and elevated PTHrP levels are associated with increased mortality in patients with hypercalcemia associated with malignancy 2.
- PTHrP is produced by cancer cells and mimics the effects of parathyroid hormone (PTH) to elevate serum calcium concentrations 3.
- The existence of amino (N)-terminal and carboxy (C)-terminal PTHrP assays and how their concentrations are impacted by chronic kidney disease (CKD) are important considerations in evaluating hypercalcemia 3.
- Many commercial labs run the C-terminal PTHrP assay as their first-line test, which can lead to inaccurate differential diagnoses in hypercalcemic patients with CKD 3.
Hypercalcemia Treatment
The treatment of hypercalcemia, particularly in patients with malignancy, often involves the use of bisphosphonates such as zoledronic acid. Key points to consider include:
- Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy 4.
- Zoledronic acid is a potent inhibitor of bone resorption and is effective in normalizing calcium levels in patients with hypercalcemia of malignancy 5, 4.
- The efficacy of zoledronic acid in reducing serum calcium levels has been demonstrated in several studies, with response rates and durations of response favoring zoledronic acid over pamidronate 4.
- Appropriate normal saline hydration with immediate intravenous bisphosphonates infusion, such as zoledronic acid, should be considered in the management of severe hypercalcemia in patients with primary hyperparathyroidism (PHPT) 6.