Endocrine Abstracts

JOINT3459

Background: Prader-Willi Syndrome (PWS) is a rare genetic disorder characterized by neonatal hypotonia, hyperphagia, obesity and multiple endocrine abnormalities, including short stature and growth hormone deficiency (GHD). In Italy, the “Note AIFA 39” regulates the use and refund of Growth Hormone (rGH) therapy by the National Health System. In PWS children treatment with rGH can be started without stimulation tests to demonstrate GHD. However, after the achievement of final height, stimulation tests must be taken to confirm GHD before resuming treatment in PWS late adolescents and adults. Most studies use the growth-hormone-releasing hormone plus arginine (GHRH-arginine) test or, less frequently, the insulin tolerance test (ITT). Due to the shortage of GHRH-arginine, starting from October 2023, AIFA authorized the use of glucagon stimulation test (GST) to assess GH status in GHD adult patients. Few data are available on GST in PWS.

Aim: This study aims to investigate GHD with GST in PWS patients during the transition phase.

Methods: We retrospectively analyzed peak GH concentrations in ten late adolescent PWS patients followed at our Center (5 males and 5 females; median age 16,1 y; median BMI 25,7 kg/m²) who underwent GST after discontinuing GH treatment for at least 4-6 weeks. These patients discontinued treatment at achievement of final height as defined by a growth velocity < 1 cm/year and the epiphyseal closure demonstrated by bone age evaluation. GHD was defined as a peak GH concentration (GHp) < 3 ng/ml.

Results: Three patients met the criteria for GHD status (peak GH concentration < 3 ng/ml) and resumed growth hormone therapy. Instead, seven patients suspended the therapy as the peak GH concentration was higher than cut-off. A moderate negative correlation was found between GHp and BMI (r = -0.52, P =0.123), suggesting that GH response decreased with increasing BMI, but no significant correlation with age was observed. Gender did not significantly influence GH response.

Conclusions: GST is a reliable, safe and inexpensive alternative to the GHRH-arginine test for diagnosing GHD in adult PWS patients. However, BMI-related criteria should be considered, especially in overweight and obese patients. Resuming GH therapy in GHD adult PWS patients during the transition phase showed positive effects in order to preserve body composition and quality of life. Further studies are needed to define the accuracy of GST for GHD screening in PWS during the transitional age.