From the Guidelines
Elevated calcium levels and increased angiotensin-converting enzyme (ACE) activity are highly suggestive of sarcoidosis, and clinicians should promptly initiate diagnostic workup and treatment to prevent long-term morbidity and mortality. When encountering this combination, clinicians should order a chest X-ray or CT scan to look for hilar lymphadenopathy and pulmonary infiltrates characteristic of sarcoidosis, as recommended by the American Thoracic Society clinical practice guideline 1. Additional testing should include 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels, 24-hour urinary calcium, and parathyroid hormone (PTH) levels to distinguish sarcoidosis from other causes of hypercalcemia, as outlined in the guideline 1.
Some key points to consider in the diagnostic workup and management of sarcoidosis include:
- Hypercalcemia is detected in 6% of patients with sarcoidosis, and renal failure develops in 42% of untreated patients 1
- Elevated ACE levels are a common finding in sarcoidosis, and can be used to support the diagnosis 1
- The elevated calcium in sarcoidosis results from increased production of 1,25-dihydroxyvitamin D by activated macrophages in granulomas, which enhances intestinal calcium absorption and bone resorption 1
- Management typically involves corticosteroids, with prednisone 20-40 mg daily for 1-3 months followed by a slow taper based on clinical response, as well as IV fluids and possibly calcitonin or bisphosphonates for rapid calcium reduction in patients with significant hypercalcemia (>12 mg/dL)
Regular monitoring of calcium levels, renal function, and ACE activity helps assess treatment response and guide therapy duration, and is essential for preventing long-term complications and improving quality of life in patients with sarcoidosis 1.
From the FDA Drug Label
The principal pharmacologic action of zoledronic acid is inhibition of bone resorption. Although the antiresorptive mechanism is not completely understood, several factors are thought to contribute to this action. In vitro, zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis Zoledronic acid also blocks the osteoclastic resorption of mineralized bone and cartilage through its binding to bone. Clinical studies in patients with hypercalcemia of malignancy (HCM) showed that single-dose infusions of zoledronic acid injection are associated with decreases in serum calcium and phosphorus and increases in urinary calcium and phosphorus excretion
Elevated Calcium and ACE: Zoledronic acid is used to treat hypercalcemia of malignancy by inhibiting bone resorption, which leads to a decrease in serum calcium levels.
- Key Points:
- Zoledronic acid inhibits osteoclastic activity and induces osteoclast apoptosis.
- It blocks the osteoclastic resorption of mineralized bone and cartilage.
- Single-dose infusions of zoledronic acid are associated with decreases in serum calcium and phosphorus. 2
From the Research
Elevated Calcium and ACE
- Elevated calcium levels, also known as hypercalcemia, can be caused by various factors, including primary hyperparathyroidism, malignancies, and granulomatous diseases such as sarcoidosis 3, 4.
- Angiotensin-converting enzyme (ACE) activity is often elevated in sarcoidosis, which can be a useful diagnostic tool in distinguishing sarcoidosis from other hypercalcemic disorders 5, 6.
- However, ACE activity is not a specific test for the differential diagnosis of hypercalcemia, as it can be elevated in other conditions as well 5.
- The predictive value of serum ACE activity in the differential diagnosis of hypercalcemia is limited, as it can be influenced by various factors, including the underlying cause of hypercalcemia and the presence of other diseases 5, 6.
- In patients with hypercalcemia, the measurement of ACE activity can be useful as a rapid diagnostic guide, especially when sarcoidosis is suspected to be the cause of hypercalcemia 6.
- The diagnosis and management of hypercalcemia depend on the underlying cause, and treatment options include hydration, bisphosphonates, and glucocorticoids 3, 4.
- Primary hyperparathyroidism is a common cause of hypercalcemia, and its diagnosis and management involve the measurement of parathyroid hormone (PTH) levels and the assessment of kidney and skeletal involvement 3, 7.