Preoperative Clinical and Biochemical Predictors ofEarly and Late Postoperative Hypocalcemia inPrimary Hyperparathyroidism

Introduction: Postoperative hypocalcemia is one of the most common complications after parathyroidectomy for Primary Hyperparathyroidism (PHPT). While early hypocalcemia is typically attributed to the sudden withdrawal of Parathyroid Hormone (PTH), late hypocalcemia often resembles Hungry Bone Syndrome (HBS) due to persistent skeletal remineralization. The mechanisms behind early and late hypocalcemia may differ, and clinical importance has been attributed to their identification. Therefore, preoperative biochemical predictors of early and late hypocalcemia post-parathyroidectomy in PHPT patients were studied. Methods: 89 patients who underwent isolated parathyroid adenoma excision at Tokat Gaziosmanpasa University Hospital between January 2015 and January 2025 were retrospectively analyzed. Patients with tertiary hyperparathyroidism, those who underwent concomitant thyroidectomy, those with chronic kidney disease, and those with missing data were excluded. Demographic and clinical features, as well as preoperative biochemical data, including corrected calcium, phosphate, alkaline phosphatase (ALP), vitamin D, and PTH, were recorded. Adenoma volume was additionally calculated to better reflect tumor burden. Early hypocalcemia was defined as corrected calcium <8.5 mg/dL within the first 3 postoperative days, while late hypocalcemia was defined as corrected calcium <8.5 mg/dL after the 4th day and postoperatively up to 3 months. Logistic regression analyses were performed to identify predictors. Results: Early hypocalcemia occurred in 21 patients (23.6%) and late hypocalcemia in 16 patients (18.0%). Eleven patients experienced both early and late hypocalcemia, whereas five developed late hypocalcemia without preceding early hypocalcemia. On univariate analysis, higher preoperative PTH, lower vitamin D, and higher corrected calcium were associated with early hypocalcemia, but only PTH remained significant in multivariate analysis (OR 1.004, 95% CI 1.000–1.008, p=0.047). Late hypocalcemia was associated with elevated PTH, ALP, corrected calcium, larger adenoma size, and lower vitamin D and phosphate. In multivariate models, preoperative PTH remained independently associated with late hypocalcemia, while adenoma volume provided additional prognostic information, suggesting a role of tumor burden in prolonged calcium decline. Discussion: In this study, PTH appeared to be the major determinant of early postparathyroidectomy hypocalcemia and late postparathyroidectomy hypocalcemia. However, late postparathyroidectomy hypocalcemia was also affected by adenoma burden, consistent with a clinical picture of hungry bone syndrome.Identification of these associations might enable earlier supplementation and more appropriate postoperative monitoring. Conclusion: Preoperative PTH may be considered the primary risk stratification parameter in the perioperative period. In this context, it may be possible to think of adenoma burden in identifying a subgroup of patients with a risk of late postoperative hypocalcemia after parathyroidectomy for PHPT.This would probably aid a more focused approach to individualized preventative strategies and improve the management of these patients in the postoperative period.