48-Year clinical experience and genetic analysis of pediatric primary hyperparathyroidism from a single center in China

Purpose This study aims to investigate the clinical and genetic features and change of clinical spectrum of primary hyperparathyroidism (PHPT) in children and adolescents. Methods The clinical and follow-up data of 74 pediatric patients (onset age <= 18 years) with PHPT during 1975-2022 were retrospectively analyzed. For comparison, patients were divided into four subgroups according to their time of diagnosis. Genetic analysis was conducted in 40 patients. Results Pediatric PHPT cases increased largely over time [34 cases (45.9%) in 2015-2022]. The rate of asymptomatic PHPT increased by time (14.7% in 2015-2022 vs. 0% before 2015), in accordance with routine screening of serum calcium becoming a more frequent reason for clinic visit (17.6% in 2015-2022 vs. 0% before 2015). Skeletal manifestation significantly decreased in recent years (64.7% in 2015-2022 vs. 100.0% in 1975-1994, P < 0.05). Sixty-seven patients (90.5%) of the whole cohort underwent parathyroidectomy. Atypical parathyroid adenoma and parathyroid carcinoma occurred in 13.4% and 4.5% of the surgical cases, respectively. Recurrence and persistence of PHPT were observed in 17.9% of postsurgical patients. Germline rare variations (RVs) of PHPT-related genes were found in 42.5% (17/40) of all cases with genetic testing. Compared with no-variation group, the variation group had higher incidence of multiple parathyroid lesions (42.8% vs. 4.3%, P = 0.014), and lower rate of benign lesions and higher rate of recurrence and persistence. Conclusion Milder cases of Pediatric PHPT are coming to clinical attention probably due to routine lab testing. Genetic testing is recommended for pediatric PHPT patients.