From the Guidelines
Hypercalcemia with normal parathyroid hormone (PTH) levels is most likely caused by non-parathyroid factors, such as malignancy, vitamin D toxicity, or granulomatous diseases, rather than primary hyperparathyroidism. According to the study by 1, accurate measurement of PTH is crucial in identifying patients with normocalcemic primary hyperparathyroidism, but in cases where PTH levels are normal, other causes must be considered.
Key Considerations
- Malignancy, particularly with PTHrP production, is a common cause of hypercalcemia with normal PTH levels
- Vitamin D toxicity, granulomatous diseases (such as sarcoidosis and tuberculosis), and certain medications (like thiazide diuretics and lithium) can also contribute to hypercalcemia
- Milk-alkali syndrome is another potential cause of hypercalcemia with normal PTH levels
Management
- Initial management involves hydration with normal saline to promote calcium excretion
- Addressing the underlying cause is crucial, whether it be discontinuing contributing medications, restricting calcium intake, or treating the underlying disease process
- For moderate to severe hypercalcemia (>12 mg/dL), bisphosphonates like zoledronic acid or pamidronate can be used, along with calcitonin for temporary relief
- Glucocorticoids like prednisone may be helpful in cases of vitamin D-mediated hypercalcemia, and denosumab may be considered in refractory cases, as supported by the principles outlined in 1.
Monitoring and Treatment
- Monitoring serum calcium, renal function, and electrolytes is essential in managing hypercalcemia with normal PTH levels
- Identifying and treating the underlying cause is key to successful management, and a thorough evaluation of non-parathyroid causes is necessary to determine the best course of treatment.
From the Research
Causes of Hypercalcemia with Normal Parathyroid Hormone (PTH) Levels
- Hypercalcemia can be caused by various conditions, including primary hyperparathyroidism (PHPT), malignancy, granulomatous disease, endocrinopathies, immobilization, genetic disorders, and certain medications or supplements 2
- In some cases, hypercalcemia can occur with normal PTH levels, which may be due to non-parathyroid conditions such as vitamin D intoxication, granulomatous disorders, or certain malignancies 3
- Hypercalcemia of malignancy (HCM) is a common cause of hypercalcemia with normal PTH levels, and can be due to the secretion of parathyroid hormone-related peptide (PTHrP) or other factors such as 1,25-dihydroxyvitamin D 3, 4
- Other causes of hypercalcemia with normal PTH levels include calcitriol-induced hypercalcemia, which can be treated with bisphosphonates 5
- In rare cases, primary hyperparathyroidism can present with hypercalcemia and undetectable PTH levels, which may be due to a genetic mutation in the PTH gene within the adenoma 6
Diagnosis and Treatment
- Serum intact parathyroid hormone (PTH) is the most important initial test to evaluate hypercalcemia, and can help distinguish between PTH-dependent and PTH-independent causes 2
- Treatment of hypercalcemia depends on the underlying cause, and may include hydration, intravenous bisphosphonates, glucocorticoids, or other medications 2, 5
- In cases of hypercalcemia with normal PTH levels, treatment may involve addressing the underlying condition, such as vitamin D intoxication or malignancy 3, 5