Endocrine Abstracts

Delayed puberty (DP) is defined as pubertal onset 2-2.5 SDs later than the general population. The most common aetiology is self-limited DP (SLDP). However, during adolescence, it is a clinical challenge to differentiate SLDP from the more severe disease congenital hypogonadotrophic hypogonadism (HH). This study sought to elucidate phenotypic and genotypic discrepancies between the two diagnoses to improve diagnosis and management. This was a retrospective study of a UK DP cohort managed from 2015-2023, identified through the NIHR clinical research network. Patients were diagnosed with SLDP if they attained Tanner stage G4/B4 by 18yrs, whereas with HH if they had not commenced (complete, cHH) or had arrested puberty (partial, pHH) before 18yrs. Auxology, Tanner staging, biochemistry, bone age, and hormonal treatment were analysed. Genetic scores, ranging from 1-5, were assigned after whole-exome sequencing and identification of predicted pathogenic variants in genes associated with either SLDP or HH (1=known SLDP variant, 2=likely SLDP variant, 3=no or overlap variant, 4=likely HH variant, 5=known HH variant). Statistical analysis was completed using IBM SPSS and R. 78 patients were included in this study. 52 (66.7%) patients had SLDP and 26 (33.3%) had HH, of whom 17 (65.4%) pHH and 9 (34.6%) cHH. Probands were predominantly male (90.4%). Male SLDP patients showed significantly lower height and weight SD at presentation (P=0.004, P=0.021). HH patients had lower testicular volumes, particularly cHH patients (P=0.019). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (P=0.007). 15.4% of SLDP, compared to 38.5% of HH patients, had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. P=0.023). Mean first recorded LH and inhibin B were lower in males with HH, particularly in cHH patients (P=0.01, P=0.001), but were not discriminatory due to overlapping ranges. Genetic score of SLDP patients was lower than HH patients (3.00±0.55 vs 3.47±0.70; P=0.008). Key clinical markers of auxology, associated signs, and serum inhibin B may help distinguish between SLDP and HH. These could be incorporated into a scoring system with genetic analysis to aid clinician’s decision-making process. However, the distinction between partial HH and SLDP remains problematic.