ESPE Abstracts

Pubertal delay in females is defined as the lack of development of Tanner breast stage 2 by 13 years of age. Recent cohort studies have recapitulated the findings of classic studies over the last few decades, that constitutional delay (also known as self-limited delayed puberty) is less common in girls than in boys. This diagnosis is found in 30% of girls presenting with delayed puberty, with a further 30% classified as functional hypogonadotropic hypogonadism due to chronic illness or undernutrition. Syndromic and isolated hypogonadotropic hypogonadism, as well as pituitary endocrine causes account for 20% and the final 20% is due to primary gonadal causes including Turner syndrome and primary ovarian insufficiency. Primary amenorrhoea may also be seen in adolescent females with hyperandrogenism as part of the spectrum of polycystic ovarian syndrome. As in males, one of the diagnostic dilemmas in clinical practice is to distinguish between self-limited delay and permanent hypogonadotropic hypogonadism in girls presenting with delayed puberty onset. Genetic diagnosis may significantly aid this distinction, especially as in girls red flags such as low testes volume, micropenis and cryptorchidism are not relevant. At present, genetic testing usually involves panel exome sequencing for common genes known to cause hypogonadotropic hypogonadism. Increasing understanding of genes underlying both self-limited delayed puberty and hypogonadotropic hypogonadism will further assist this strategy and in the future whole exome or genome sequencing in such patients may be adopted. Biochemical biomarkers such as inhibin B and AMH may also be of diagnostic value in adolescent females, as well as prognostic indicators of future fertility potential with correlation with oocytes number. Mini-puberty provides a window of opportunity for the diagnosis of both hyper and hypogonadotropic hypogonadism in female infants, with recent publication of high quality normative data. The understanding of the physiological role of mini-puberty in females, and the interpretation of pathology is still limited and requires further study.