From the Guidelines
Elevated calcium levels in conjunction with mid to high normal parathyroid hormone (PTH) levels and very high 25-hydroxyvitamin D levels may indicate vitamin D toxicity or hypervitaminosis D, potentially caused by excessive supplementation 1. This condition can lead to hypercalcemia, which may require discontinuation of vitamin D supplements.
- The desirable serum 25-hydroxyvitamin D (25-OH-D) levels are not well established, but levels above 75 nmol L−1 may be considered excessive 1.
- Primary hyperparathyroidism should be ruled out, especially if PTH levels are elevated and serum calcium levels are high 1.
- Treatment may involve discontinuation of vitamin D supplements and potentially treatment with glucocorticoids, such as prednisone, to reduce calcium levels.
- Monitoring of PTH, calcium, and 25-hydroxyvitamin D levels every 3-6 months is recommended to assess the effectiveness of treatment and prevent long-term complications.
- It is essential to note that all individuals are at risk of developing vitamin D deficiency, especially after bariatric surgery, but those with more malabsorptive procedures are at greater risk 1.
From the Research
Interpretation of Laboratory Results
- Mid to high normal Parathyroid Hormone (PTH) levels, elevated calcium levels (hypercalcemia), and very high 25-hydroxyvitamin D (25-OH-D) levels can be indicative of several conditions, including primary hyperparathyroidism (PHPT) 2, 3, 4.
- Hypercalcemia is defined as a serum calcium concentration >10.5 mg/dL and can be caused by various factors, including excessive PTH production, production of parathyroid hormone-related protein (PTHrp), bone metastasis, extrarenal activation of vitamin D, and ectopic PTH secretion 5.
- Very high 25-OH-D levels can contribute to hypercalcemia, as 25-OH-D can bind to the vitamin D receptor and increase calcium absorption in the gut 6.
Possible Causes
- Primary hyperparathyroidism (PHPT) is a condition characterized by the autonomous production of PTH, leading to hypercalcemia or normal-high serum calcium levels, and elevated or inappropriately normal serum PTH concentrations 2, 3, 4.
- Vitamin D-mediated hypercalcemia can occur due to excessive ingestion of vitamin D, ectopic production of 1,25-dihydroxyvitamin D, or impaired degradation of 1,25-dihydroxyvitamin D 6.
- Other possible causes of hypercalcemia include malignancies, granulomatous diseases, and familial hypocalciuric hypercalcemia (FHH) 5, 6, 3.
Diagnostic Considerations
- The diagnosis of PHPT is biochemical and requires the measurement of PTH, calcium, phosphate, and 25-OH-D levels 2, 4.
- A definitive diagnosis of PHPT can only be made by demonstrating persistent hypercalcemia or normal-high serum calcium levels in the presence of inappropriately normal or elevated serum PTH concentrations 2.
- The differential diagnosis of PHPT includes other causes of hypercalcemia, such as tumoral hypercalcemia, granulomatous disease, and vitamin D or A intoxication 2.