A. J. Lowell1, N. M. Bushman1, X. Wang1, Y. Ma1, R. S. Sippel1, S. C. Pitt1, D. F. Schneider1, R. W. Randle1 1University Of Wisconsin,Department Of Surgery,Madison, WI, USA
Introduction: Hypercalcemic crisis (HC) is a rare, potentially life-threatening complication of hypercalcemia. Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia and can manifest as hypercalcemic crisis. This study aims to identify patients with PHPT at greatest risk for developing HC.
Methods: This retrospective cohort study included patients with a pre-operative calcium of at least 12 mg/dL undergoing initial parathyroidectomy for PHPT from 11/2000–03/2016. This cohort was then separated into two groups: 1) those with HC, defined as those patients hospitalized and treated for hypercalcemia, and 2) those without HC. We compared the two groups using Mann-Whitney U tests and chi-squared tests where appropriate. Multivariable logistic regression identified predictors of HC. Additionally, we performed a classification tree (CART) analysis to produce a decision tool that can classify patients by risk of HC.
Results: Of the patients meeting inclusion criteria, 29 (15.8%) had HC and 154 (84.2%) did not. The two cohorts were similar in age, gender, alcohol use, smoking status, BMI, and Charlson comorbidity index (CCI). Patients with HC were more likely to have a history of kidney stones than patients without HC (31.0% vs. 14.3%; P=0.039). Compared to those without HC, patients with HC also had higher pre-operative calcium (median 13.8 vs. 12.4 mg/dL; P<0.001), higher pre-operative parathyroid hormone (PTH) (median 318 vs. 160 pg/mL; P=0.001), and lower pre-operative total vitamin D (median 16 vs. 26 ng/mL; P<0.001). Cure rates with parathyroidectomy were similar in both groups, but nearly double the proportion of patients with HC required resection of more than one gland compared to patients without HC (24.1 vs. 12.3%, P=0.12). In multivariable analysis, higher pre-operative calcium (Odds Ratio [OR] 1.7, 95% Confidence Interval [CI] 1.1-2.5, P=0.01), elevated PTH (OR 1.0, 95% CI 1.0-1.0, P=0.01), and history of kidney stones (OR 3.0, 95% CI 1.1-8.2, P=0.04) were independently associated with HC. The CART decision tree (Figure 1) revealed that over 90% of patients with a calcium ≥ 13.25 mg/dL and a CCI ≥ 4 developed HC. Additionally, 60% of patients with calcium ≥ 13.25, CCI < 4, and PTH ≥ 394 also had crisis. The CART model carried an overall predictive accuracy of 90%, and a positive predictive value of 76%.
Conclusion: These data indicate that patients with calcium ≥ 13.25, PTH ≥ 394, and a CCI ≥ 4 are at increased risk for developing HC. The decision tool reported here can help identify patients at greatest risk for developing HC, and allow surgeons to expedite parathyroidectomy accordingly.
