High Prevalence of Hypercalcitoninemia in a Large Cohort of Adult and Pediatric Patients With PTH Resistance Syndromes

Abstract Context Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathyroid hormone (PTH) and other hormones now termed inactivating PTH/PTHrP disorders (iPPSD). Hypercalcitoninemia has been seldom reported in small series. Objective Our aim was to investigate the characteristics of hypercalcitoninemia in pediatric and adult patients with PHP/iPPSD. Methods We retrospectively collected data from 2 cohorts from 2 European endocrinology tertiary centers: the pediatric cohort comprised 88 children with available calcitonin (CT) measurements; the adult cohort included 43 individuals with simultaneous CT and PTH measurements. Results In the pediatric cohort, 65.9% had hypercalcitoninemia (median CT 15 ng/L); in the adult cohort 53.5% (mean CT 21.6 ng/L). There was no difference between CT in pediatric and adult population; we observed stable CT levels over a median follow-up of 134.5 months in adults. Notably, no correlations were detected between CT and PTH levels. Other etiologies of hypercalcitoninemia were excluded; adult patients underwent regular thyroid ultrasound to screen for medullary thyroid cancer (MTC). We performed 20 calcium stimulation tests in adult patients. While there was a significant difference in basal and peak CT between our patients, healthy subjects, and subjects with MTC, there was no difference with patients with C-cell hyperplasia. Conclusion This study underscores the common occurrence of hypercalcitoninemia in both pediatric and adult patients with PHP/iPPSD, in particular with subtypes iPPSD2 and iPPSD3. Furthermore, these patients show hyperresponsiveness to calcium stimulation tests falling between healthy subjects and patients with MTC. These findings contribute to the understanding of CT dynamics in the context of PHP/iPPSD.