From the Guidelines
High levels of 1,25-dihydroxyvitamin D (calcitriol) with hypercalcemia typically indicate granulomatous disease, lymphoma, or vitamin D toxicity, and initial management should focus on treating the underlying condition, hydration, and limiting calcium and vitamin D intake. The most common granulomatous cause is sarcoidosis, where activated macrophages produce excess calcitriol outside of normal regulatory control. According to the study by 1, treatment approaches for CKD-MBD should be based on serial assessments of biochemical variables, including serum phosphate, calcium, and PTH, taken together.
Key Considerations
- Hypercalcemia may be harmful in all GFR categories of CKD, prompting the recommendation to avoid inappropriate calcium loading in adults whenever possible 1.
- The use of calcium-based phosphate binders should also be restricted in patients with hyperphosphatemia across the CKD spectrum 1.
- Treatment approaches for SHPT in patients not receiving dialysis should not include routine use of calcitriol or vitamin D analogues due to the increased risk for hypercalcemia 1.
Management
- Initial management includes treating the underlying condition, hydration with normal saline (2-4 liters daily), and limiting calcium and vitamin D intake.
- For severe hypercalcemia (>12 mg/dL), bisphosphonates like zoledronic acid (4 mg IV) or pamidronate (60-90 mg IV) may be needed.
- Corticosteroids (prednisone 20-40 mg daily) are particularly effective for granulomatous causes as they suppress the abnormal calcitriol production.
- Calcitonin (4-8 IU/kg SC every 12 hours) can provide rapid but temporary calcium reduction.
Monitoring
- Monitoring calcium levels every 1-2 days during acute management is essential, with follow-up 1,25-dihydroxyvitamin D levels to assess treatment response.
From the Research
Causes of Hypercalcemia and Elevated 1,25-Dihydroxyvitamin D
- Hypercalcemia can occur due to various reasons, including conventional therapy with calcium and calcitriol, secondary hyperparathyroidism, low turnover bone diseases, and immobilization, especially in dialysis patients 2.
- Fungal infections, such as pulmonary cryptococcosis, can also lead to hypercalcemia mediated by extrarenal overproduction of 1,25-dihydroxyvitamin D (1,25(OH)2D) 2.
- Granulomatous disorders, including granulomatous myositis and Crohn's disease, can cause hypercalcemia due to excessive 1α-hydroxylase activity and subsequent overproduction of 1,25(OH)2D 3, 4.
- Acromegaly, a condition characterized by growth hormone excess, can also lead to 1,25-dihydroxyvitamin D-dependent hypercalcemia, as seen in case reports and literature reviews 5.
Mechanisms and Associations
- The overproduction of 1,25(OH)2D in granulomatous diseases is controlled by glucocorticoids and can lead to increased intestinal absorption of calcium, enhanced bone resorption, and hypercalcaemia or hypercalciuria 6.
- Elevated angiotensin-converting enzyme (ACE) levels have been reported in patients with sarcoidosis and active Crohn's disease, and may be associated with hypercalcemia 4.
- The measurement of vitamin D metabolites is crucial in diagnosing 1,25-dihydroxyvitamin D-mediated hypercalcemia, and glucocorticoid therapy can be effective in treating this condition 3.
Clinical Presentations and Treatment
- Hypercalcemia due to 1,25-dihydroxyvitamin D overproduction can present with severe hypercalcemia, generalized weakness, and other symptoms, and may require antifungal treatment or glucocorticoid therapy 2, 3.
- In cases of acromegaly, complete resection of the pituitary tumor can lead to biochemical remission and normalization of calcium and 1,25(OH)2D levels, while incomplete resection may result in persistent hypercalcemia 5.