Clinical Features and Assessment of the Pathway-Care Proposed by ISPED-Gsa Study Group in an Pediatric Italian Cohort with Pseudohypoparathyroidism

Background and objective: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of rare endocrine disorders caused by genetic or epigenetic abnormalities affecting the GNAS locus. It is mainly characterized by resistance to PTH and TSH and a complete or partial Albright Hereditary Osteodistrophy (AHO) phenotype. Few data so far exist on LH/FSH, calcitonin and glucose-lipid metabolism involvement, as well as on neurocognitive aspects. The aim of this multicentre study is to explore prevalence and management of these less studied PHP features, according to the recently published pathway care proposed by the Italian Society of Pediatric Endocrinology and Diabetology (ISPED). Methods: Twenty-three PHP patients followed by 4 Italian Pediatric Endocrine Centres were enrolled, 14 of which have genetic/ epigenetically been characterized. Data on auxological variables, calcium-phosphorus metabolism, thyroid function, FSH/LH, calcitonin, glucose-lipid metabolism, ossifications and neurocognitive development were collected through a common standardized chart. Results: The average age of the considered population was 12 yrs (6 yrs at diagnosis); 60.8% of patients displays overweight or obesity (average BMI 23.32, +1.44 SDS) and 23.8% show height <-2SDS (average 138.25 cm, -1.14SDS), 60% of which also had IGF1 <0 SDS; 3 patients have performed GH-stimulation tests, with low GH response resulting eligible for hrGH-therapy. At diagnosis, 90.5% of patients show increased PTH, 47.6% hypocalcemia and 66.7% hyperphosphatemia; after oral supplementation with 1,25-VitD alone or associated with calcium, the prevalence of these alterations decreases to 76.2%, 0% and 33.3% respectively; bone mineralization was appropriate in all patients. Clinical hypothyroidism was present in 8 patients (61.5%) at diagnosis; after substitutive therapy a subclinical form remained in 23.1%. FSH/ LH resistance has been found in 30.8%, Calcitonin increased levels in 50% of the whole cohort. Glucose metabolism was normal in most patients (euglycemia in 94.7% and normal glucose tolerance in 5/6 patients, with 1 case only with type1-diabetes); 22.2% showed hypercholesterolemia, 11.1% hypertriglyceridemia and 77.8% reduced HDL-cholesterol levels. Heterotopic ossification was described in 45.5% of patients, delayed verbal-motor skills acquisition and/or intellectual disability in 63.2%, psychological support needs in 23.5%. Conclusions: A standardized approach to the PHP patients, according to ISPED-Care pathway, seems a valid instrument to detect and manage the clinical features of this heterogeneous disorder, aimed to guarantee the same and best assistance to all patients