Calcitriol-Mediated Hypercalcemia: Causes and Course in 101 Patients

Context: Hypercalcemia mediated by 1,25-dihydroxy vitamin D (calcitriol) is uncommon, with evidence on etiology limited to small case series or case reports. Objective: The objective of the study was to systematically identify a large series of cases of calcitriol-mediated hypercalcemia and document the presentation, demographics, and clinical course across etiologies. Design, Setting, and Patients: The study was a hospital-based, retrospective case series, identifying subjects from 1999 through 2009 across the public hospital system in Queensland, Australia. All patients aged over 18 years were identified that had persistent hypercalcemia associated with elevated or inappropriately normal calcitriol concentration or elevated serum angiotensin-converting enzyme. Results: A total of 101 cases were identified. Sarcoidosis was the most common etiology (49%), followed by hematological malignancy (17%) and infections (8%). Etiologies not previously described include squamous cell carcinoma of the tongue, ovarian cystadenocarcinoma, and chronic lymphocytic leukemia. Median serum angiotensin-converting enzyme was higher in sarcoid patients compared with all other causes [218 U/L (176-277) vs 155 U/L (110-208), P < .001], but a level above the normal range did not discriminate well between cases of sarcoidosis and other causes (specificity at cutoff of 130 U/L was only 31%). However, a value greater than 250 U/L was highly specific (89%) for sarcoidosis but lacked sensitivity (31%). A calcitriol level greater than 300 pmol/L was not seen in sarcoidosis but was seen with other etiologies. Cases with neoplastic etiologies were older (61.4 +/- 11.4 y) than all other subjects (51.7 +/- 15.0 y, P = .006). Conclusions: Hypercalcemia mediated by calcitriol remains a rare presentation. In almost half the cases, sarcoidosis was the underlying cause, whereas a third of patients had cancer or systemic infections.