Gonadotropin-Releasing Hormone Studies to Assess Pubertal Deficiencies in Prader-Willi Syndrome

Abstract

Patients with Prader-Willi Syndrome (PWS) are known to have variable pubertal development with most having delayed or incomplete puberty. This study aims to evaluate the activity of the Hypothalamic-Pituitary-Gonadal (HPG) axis in individuals with PWS. Thirty-five patients (18 males, 17 females) ages ranging from 3 to 38 years with genetically verified PWS underwent GnRH stimulation testing using gonadorelin along with clinical evaluations. Of patients in the typical age range for initiation of puberty, six had LH peak >5IU/L, indicating activation, but the remaining six had variable peaks, indicating lack of, or indeterminate activation. In some females, physical examination noted breast development to Tanner stage II to III, despite apparent lack of HPG axis activation, while in some males testicular volumes were smaller than expected despite apparent activation of the HPG axis. We studied genotype differences (deletion vs UPD) with respect to HPG axis activation. Mean LH levels were nearly double for PWS females with UPD compared to PWS females with deletion. Both peak LH and peak FSH levels appear to be higher in males with deletion compared to UPD. Inconsistency between physical examination and stimulation testing results and the high variability in the age at activation of the HPG axis accentuates the need for the evaluation of pubertal staging in patients with PWS, and consideration of sex-steroid supplementation.