ESPE Abstracts

Background: Since the first description of inactivating PTH/PTHrP signaling disorders [(iPPSD, former pseudohypoparathyroidism (PHP)] a remarkable clinical variability was observed, apparently age-dependent. The main clinical features, including PTH resistance, brachydactyly and short stature, develop during middle and late childhood. Hearing loss (HL) is commonly found in iPPSD/PHP. Only a few studies approached the subject of hearing loss in iPPSD/PHP and these have yielded largely divergent conclusions, presumably due to the small size of the investigated cohorts.

Objectives: The aim of our monocentric, prospective study was to analyze the auditory from 44 iPPSD/PHP. Children and adults affected by either iPPSD/PHP and followed in the pediatric or adult departments of endocrinology were included.

Methods: Prospective demographic, clinical data and results of auditory investigations for 44 patients with iPPSDs, followed between March 2019 and May 2020 in the Otolaryngology department and the Calcium Phosphate reference centers for rare diseases at Bicêtre Paris-Saclay Hospital, France, were collected. Air and bone conduction hearing thresholds were determined between 125 and 8000 Hz per octave frequency (125, 250, 500, 1000, 2000, 4000 and 8000 Hz). Hearing thresholds were also analysed by frequency. We analysed the prevalence and predictive factors of hearing loss. Student’s T-test or Mann-Whitney test and chi-squared test were used. Clinical predictive factors of HL were assessed using a generalized estimating equation model (GEE), with a threshold of 20 db. The results were compared to hearing norms according to the age and the gender. The primary outcome was the pure-tone average (PTA) calculated as the average of the hearing thresholds at the frequencies of 500, 1000, 2000 and 4000 Hz.

Results: Median [QR] for age at auditory investigations was 15.6 years [9.5, 28.5] (range 3.5 to 56.3 years). Thirty-six patients were diagnosed with iPPSD2 and eight with iPPSD3. Twenty-six of them (59%) were female. Age was correlated to HL (P=0.04). Short stature and the presence of ectopic ossifications were significant predictive factors of hearing loss (P=0.009 and P=0.03 respectively). Eighty-eight ears were considered for the analysis of audiograms. Hearing impairment was confirmed in 17 patients (39%) and 26 ears (30%). The mean difference of PTA between the patients and the norms was 11.4 db (P=0.00002).

Conclusion: We confirm the presence of hearing loss in iPPSD/PHP (prevalence=39%). The combination of short stature and the presence of ectopic ossifications should initiate investigations and auditory follow-up from childhood in iPPSD/PHP.