Endocrine Abstracts

Inactivating PTH/PTHrP signaling disorders (iPPSDs, historically named pseudohypoparathyroidism (PHP)) are a group of rare disorders associated with resistance to parathormone (PTH) and other hormones due to impaired hormonal signaling via G protein coupled receptors. Hypercalcitoninemia has been reported in these patients, however very few reports are available. The aim of this study was to further investigate the prevalence and characteristics of hypercalcitoninemia in both paediatric and adult iPPSD patients. We retrospectively collected data from two cohorts of iPPSD patients, both in regular follow-up at two European Endocrinology tertiary centres. The first cohort included 88 paediatric patients with available calcitonin (CT) measurements, and the second consisted of 43 adult patients with at least one simultaneous measurement of CT and PTH. In the latter cohort, c-cell function was assessed by calcium stimulation test in 19 patients. In the paediatric cohort 65.9% had hypercalcitoninemia with mean basal CT levels of 24.9±26.8 ng/l, 12.1% developed hypercalcitoninemia before the age of 2 and 65.5% before the age of 10. In the adult cohort, 53.5% had hypercalcitoninemia with mean CT levels of 21.6±8.3 ng/l. Calcitonin measurements remained stable throughout a mean follow-up time of 59±47.3 months. No correlations were detected between CT levels and PTH levels (P=0.5). Other etiologies of hypercalcitoninemia were excluded, i.e. renal failure and drug interferences, and all patients underwent regular thyroid ultrasound to screen for medullary thyroid cancer (MTC). We also performed calcium stimulation test in 19 patients and we compared CT levels with a control group of 33 healthy patients and a group of 20 patients with pathological evidence of MTC or c-cell hyperplasia (MTC-CCH). We found that there was a statistically significant difference in both basal (P=0.034) and stimulated (P=0.002) CT levels in control and iPPSD groups, as well as control and MTC-CCH group (basal CT levels P=0.000; stimulated CT levels P=0.000), on the contrary there was no significant difference in both values in iPPSD and MTC-CCH group. Our study confirms that elevated calcitonin levels are commonly found in both adult and paediatric patients with PTH-resistance syndromes. Our findings suggest that it may be a condition that develops in early age and remains stable throughout time. Moreover, these patients show an hyperresponsiveness to calcitonin stimulation test. Differential diagnosis with MTC based on CT levels, both basal and stimulated, can be challenging.