Intraoperative PTH monitoring: does sampling site or assay generation matter?

Context: Primary hyperparathyroidism (PHPT) is a common endocrine disorder for which minimally invasive parathyroidectomy (MIP) is the standard surgical approach. Intraoperative parathyroid hormone (IOPTH) monitoring is commonly performed using second-generation (2G) parathyroid hormone (PTH) assay. Objective: To compare the performance of IOPTH central sampling peripheral sampling, and third-generation (3G) vs 2G assays in patients with PHPT. Methods: This is a prospective cohort study conducted at American University of Beirut Medical Center, a tertiary hospital in Beirut, Lebanon. The study included 68 subjects with confirmed PHPT who achieved surgical cure, defined as normocalcemia at ≥6 months. IOPTH levels were measured from central and peripheral venous samples using 2G and 3G assays at various time points. Results: The median age was 57 years, and 80% were female. One-fourth had osteoporosis or reported kidney stones. Median preoperative calcium was 10.8 mg/dL with PTH 104 pg/mL, and 82% had single-gland disease. IOPTH levels were significantly higher with 2G assay and central sampling vs 3G assay and peripheral sampling. The proportion of patients meeting the Miami criterion did not differ between assays or sampling sites. Median percentage drop in IOPTH was greater with the 3G assay compared to 2G, across all time points, at both sampling sites. Conclusion: Although both assays similarly identified a ≥50% intraoperative decline, 3G assays demonstrated a steeper and more consistent drop, suggesting that higher assay-specific thresholds may improve decision-making. Central and peripheral sampling showed comparable predictive performance, although central sampling may allow earlier detection of PTH decline.