1,25-dihydroxyvitamin D-mediated hypercalcemia associated with solid organ malignancy: a systematic review

Area of Science:

• Endocrinology
• Oncology
• Nephrology

Background:

• 1,25-dihydroxyvitamin D [1,25(OH)2D]-mediated hypercalcemia is increasingly recognized in solid organ malignancies, beyond its known association with lymphoma and granulomatous disorders.
• Understanding this association is crucial for accurate diagnosis and management of hypercalcemia in cancer patients.

Purpose of the Study:

• To systematically review and summarize existing evidence on 1,25(OH)2D-mediated hypercalcemia in patients diagnosed with solid organ malignancies.
• To categorize the strength of evidence linking tumor-associated 1,25(OH)2D production to hypercalcemia.

Main Methods:

• A systematic literature search was conducted on MEDLINE and EMBASE databases (up to December 2020) using terms for Vitamin D, Hypercalcemia, and Malignancy.
• Included were case reports and case series detailing patients with solid organ malignancy, hypercalcemia, and elevated 1,25(OH)2D, excluding other causes.
• Cases were classified as 'definite,' 'probable,' or 'possible' based on established criteria assessing the tumor's role in 1,25(OH)2D overproduction.

Main Results:

• The review identified 17 articles reporting on 17 patients with 11 distinct types of solid organ malignancies.
• All identified cases presented with hypercalcemia secondary to elevated 1,25(OH)2D levels.
• Of the 17 cases, 4 were classified as 'definite' and 13 as 'probable' for 1,25(OH)2D-mediated hypercalcemia.

Conclusions:

• This systematic review confirms the occurrence of hypercalcemia due to elevated 1,25(OH)2D in patients with various solid organ malignancies.
• The findings underscore the importance of considering vitamin D dysregulation in the differential diagnosis of hypercalcemia in oncology settings.