From the Guidelines
Patients with sarcoidosis should undergo baseline serum calcium testing to screen for abnormal calcium metabolism, even in the absence of symptoms or signs of hypercalcemia, as recommended by the American Thoracic Society clinical practice guideline 1.
Importance of Calcium Level Monitoring
Hypercalcemia occurs in approximately 10-20% of patients with sarcoidosis and should be monitored regularly. The elevated calcium levels result from increased production of 1,25-dihydroxyvitamin D by activated macrophages in granulomas, leading to enhanced intestinal calcium absorption and bone resorption.
Treatment Approach
First-line treatment for hypercalcemia in sarcoidosis is corticosteroids, typically prednisone at 20-40 mg daily for 1-2 months, followed by a gradual taper based on calcium level response, as suggested by the Delphi consensus recommendations 1.
- Patients should also be advised to:
- Avoid excessive vitamin D and calcium supplementation
- Limit sun exposure
- Maintain adequate hydration
- For those who cannot tolerate or respond to corticosteroids, alternatives include:
- Hydroxychloroquine (200-400 mg daily)
- Methotrexate (10-25 mg weekly)
Monitoring and Complications
Regular monitoring of serum calcium, 25-hydroxyvitamin D, and renal function is essential during treatment 1. Severe hypercalcemia (>14 mg/dL) may require hospitalization for IV hydration and possibly bisphosphonates. Persistent hypercalcemia can lead to nephrocalcinosis, kidney stones, and renal dysfunction, so prompt treatment is important.
From the Research
Calcium Levels in Sarcoidosis
- Hypercalcemia is a common complication of sarcoidosis, with a prevalence of 2-63% in patients with the disease 2.
- The prevalence of hypercalcemia may vary due to the undulating course of subacute sarcoidosis, and hypercalciuria appears to be twice as prevalent as hypercalcemia 2.
- Hypercalcemia in sarcoidosis is caused by the uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages, leading to increased absorption of calcium in the intestine and resorption of calcium in the bone 2, 3, 4, 5.
Treatment of Hypercalcemia
- Treatment of hypercalcemia depends on the serum level and persistence of hypercalcemia, and may include avoiding sun exposure, omitting fish oils rich in vitamin D, and increasing fluid intake to produce more than two liters of urine per day 2.
- Glucocorticosteroids are the primary treatment for hypercalcemia, and act by inhibiting the overly active 1alpha-hydroxylase activity of macrophages 2, 3, 4, 5.
- Alternative treatments for hypercalcemia include chloroquine, ketoconazole, and infliximab, which may be used in patients who do not respond to glucocorticosteroids or have severe side effects 2, 6, 4, 5.