Endocrine Abstracts

Background: Bisphosphonates are effective in malignancy-related hypercalcemia and have been beneficial in parathyroid-hormone (PTH)-dependent hypercalcemia in small randomized-controlled trials. However, data regarding efficacy and safety in PTH-dependent hypercalcemia is limited, and pamidronate is not indicated for this condition.

Objective: To evaluate efficacy and safety of pamidronate in moderate-severe PTH-dependent hypercalcemia. Control groups were patients with PTH-dependent hypercalcemia who did not receive pamidronate, and patients with PTH-independent hypercalcemia who received pamidronate.

Methods: Medical charts of patients hospitalized with hypercalcemia >12 mg/dl between 2014 and 2019 were reviewed. Cases were categorized as PTH-dependent or PTH-independent. Epidemiological and clinical characteristics, laboratory findings including albumin-corrected calcium, creatinine and phosphorus levels, and treatments were extracted. Patients with PTH-dependent hypercalcemia who received pamidronate were compared with similar patients who did not receive pamidronate, and with patients with PTH-independent hypercalcemia who received pamidronate.

Results: There were 37 hospitalizations in 34 patients with PTH-dependent hypercalcemia; pamidronate was given in 24 cases (64.8%). Calcium at admission was higher in the pamidronate-treated group than in the untreated group (mean 14.4 mg/dl vs 13.0 mg/dl, P = 0.001); baseline creatinine and phosphorus levels were similar. Nadir post-treatment calcium was similar between groups (10.9 mg/dl vs 11.4 mg/dl respectively, P = 0.247), however the calcium delta was higher in the pamidronate-treated group (3.5 mg/dl vs 1.6 mg/dl, P = 0.003). Of pamidronate-treated patients, none developed hypocalcemia or renal failure; nadir phosphorus was lower than in untreated patients (1.7 mg/dl vs 2.4 mg/dl, P = 0.005). Sixteen patients underwent parathyroidectomy in the year following hospitalization. Regarding PTH-independent hypercalcemia, pamidronate was given to 60 patients in 67 hospitalizations; 64 cases were malignancy-related. Patients with PTH-independent hypercalcemia were older than their counterparts with PTH-dependent hypercalcemia (73.9 vs 62.4 years respectively, P<0.001). There were no between-group differences in calcium (14.8 mg/dl vs 14.4 mg/dl respectively, P = 0.278) or creatinine at admission; the PTH-dependent group had lower phosphorus (2.48 mg/dl vs 3.54 mg/dl, P<0.001). Median pamidronate dose was 60 mg in both groups. Additional treatments included fluids (97.8%), furosemide (51.6%), calcitonin (45.1%) and cinacalcet (3.3%) with no between-group differences. Of PTH-independent cases, 36 (53.7%) received glucocorticoids; few received immediate oncological therapy. Following treatment, calcium fell by 4.48 mg/dl (PTH-independent) vs 3.51 mg/dl (PTH-dependent), P = 0.048 and by >2 mg/dl in 53 (82.8%) vs 18 (75%) respectively, P = 0.408. Forty-eight patients in the PTH-independent group and 2 in the PTH-dependent group died within 1 year.

Conclusion: The efficacy of pamidronate was similar in PTH-dependent and PTH-independent hypercalcemia, with no significant documented side-effects in the PTH-dependent group. Pamidronate should be considered part of the treatment arsenal in moderate-severe PTH-dependent hypercalcemia.