Biochemical similarity but different clinical impact: could hypercalcemic crisis indicate different primary hyperparathyroidism phenotypes?

Abstract Background This study investigated whether hypercalcaemic crisis (HCC) represents a distinct phenotype shaped by the interaction between host vulnerability and tumour biology in primary hyperparathyroidism (PHPT). Methods This retrospective cohort included HCC ( n = 31) and non-HCC PHPT patients ( n = 369) (September 2023–May 2025). HCC was defined as albumin-corrected serum calcium ≥ 14 mg/dL with emergency department presentation. Pre-HCC calcium was the last value measured before the crisis. Binary logistic regression and ROC analysis were performed. Results Median PHPT duration before HCC was 64 months. Pre-HCC baseline PTH levels were similar (122 vs. 127 ng/L, p = 0.3), whereas calcium levels (10.6 vs. 11.2 mg/dL, p < 0.001) were lower in HCC patients compared non-HCC patients. Patients with HCC were older, more frequently male, and had lower BMI values (all p < 0.05). Hypertension (90.3% vs. 68.0%, p = 0.008), coronary artery disease (51.6% vs. 27.9%, p = 0.006), renal impairment (eGFR < 60 mL/min: 48.4% vs. 13.0%, p < 0.001), femoral osteoporosis (35.5% vs. 18.2%, p = 0.029), lumbar osteoporosis (54.8% vs. 30.4%, p = 0.01) and vertebral compression fractures (9.7% vs. 0.3%, p = 0.002) were more prevalent in the HCC group. Parathyroid lesions were larger in HCC patients (18 vs. 12 mm, p < 0.001), and lesion diameter was independently associated with HCC. ROC analysis identified a parathyroid lesion diameter cut-off of 11.5 mm, with a sensitivity of 96.8% and a specificity of 45.8%. Conclusions Larger parathyroid lesions were associated with HCC, alongside a greater burden of cardiovascular and renal disease. The specificity of the 11.5-mm cut-off limits its usefulness for risk assessment, warranting independent validation.