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

INTRODUCTION: A growing amount of evidence has suggested that 1,25-dihydroxyvitamin D [1,25(OH)₂D]-mediated hypercalcemia can be found not only in lymphoma and granulomatous disorders, but also in solid organ malignancies. Using systematic review technique, we aimed to summarize all available evidence of possible 1,25(OH)₂D-mediated hypercalcemia in patients with solid organ malignancies. EVIDENCE ACQUISITION: Potentially eligible articles were identified from MEDLINE and EMBASE databases from inception to December 2020 using search strategy consisting of terms related to “Vitamin D,” “Hypercalcemia” and “Malignancy.” Eligible article must be either case report or case series that reports individual level data of a patient or patients with hypercalcemia associated with solid organ malignancy and elevated 1,25(OH)₂D without concomitant conditions that may otherwise explain 1,25(OH)₂D-mediated hypercalcemia. Characteristics of the patients were extracted from each study. Eligible cases were categorized into three groups, including “definite,” “probable” and “possible” cases, using the criteria to assess the strength of evidence that hypercalcemia observed in the eligible cases was caused by the presence of tumor that resulted in the increased production of 1,25(OH)₂D. EVIDENCE SYNTHESIS: A total of 1673 articles were identified. After systematic review, 17 articles reporting 17 patients with 11 different types of solid organ malignancies associated with hypercalcemia secondary to elevated 1,25(OH)₂D were identified. Based on the criteria to assess the strength of evidence of hypercalcemia mediated by tumor-associated increased production of 1,25(OH)₂D, there were 4 definite cases and 13 probable cases. CONCLUSIONS: This systematic review of case reports and case series revealed 17 patients with 11 different types of solid organ malignancies associated with hypercalcemia and elevated 1,25(OH)₂D.