From the Guidelines
High calcium with normal PTH levels is most likely due to malignancy, and immediate management should include hydration with intravenous normal saline and consideration of bisphosphonates. The patient's presentation with high calcium and normal PTH levels suggests a non-parathyroid cause of hypercalcemia, with malignancy being a common etiology, particularly in patients with lung cancer, as seen in the study by 1. The study highlights that hypercalcemia occurs in 10% to 25% of patients with lung cancer and is most commonly seen in patients with squamous cell lung cancer. Key points to consider in the management of hypercalcemia include:
- Hydration with intravenous normal saline at 200-300 mL/hour to promote calcium excretion
- Discontinuation of any contributing medications
- Treatment of the underlying cause
- Consideration of loop diuretics, such as furosemide, after adequate hydration to further enhance calcium elimination
- Use of bisphosphonates, such as zoledronic acid or pamidronate, for severe hypercalcemia
- Evaluation for occult malignancy, including complete blood count, comprehensive metabolic panel, vitamin D levels, PTH-related protein, serum and urine protein electrophoresis, chest imaging, as mentioned in the study by 1. It is essential to address the immediate hypercalcemia while investigating the underlying cause, as normal PTH levels indicate the parathyroid glands are appropriately suppressed in response to the elevated calcium.
From the Research
High Calcium with Normal PTH
- High calcium levels with normal parathyroid hormone (PTH) levels can be caused by various factors, including hypercalcemia of malignancy, vitamin D intoxication, and granulomatous diseases such as sarcoidosis 2.
- In patients with hypercalcemia, an elevated or normal PTH concentration is consistent with primary hyperparathyroidism (PHPT), while a suppressed PTH level indicates another cause 2.
- Mild hypercalcemia usually does not need acute intervention, but if due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement 2.
- Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 2, 3, 4.
- Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas) 2.
Diagnosis and Treatment
- Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, distinguishing PTH-dependent from PTH-independent causes 2.
- A structured approach to evaluating patients with elevated PTH and normal serum calcium levels includes calculating adjusted calcium, assessing dietary calcium intake, and measuring 25-hydroxyvitamin D (25OHD) levels 5.
- Zoledronic acid is a highly potent bisphosphonate that can be used to treat hypercalcemia of malignancy, with improved efficacy compared to pamidronate disodium 4.
- The pathophysiology of hypercalcemia involves dysregulated PTH production, parathyroid hormone-related protein, and other cytokines and mediators that can cause resorptive hypercalcemia 6.