ESPE Abstracts

Background: The immunoglobulin superfamily member 1 (IGSF1) gene encodes a plasma membrane glycoprotein enriched in pituitary and testes. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism (CeH), macroorchidism, and delayed pubertal rise of testosterone despite normal timing of testicular growth. This syndrome was discovered in patients with CeH; therefore, it is presently unknown whether IGSF1 mutations also cau...

Objectives: Several different pathogenic mechanisms may converge on a final common pathway to produce the phenotype of delayed pubertal timing. In our cohort of patients with familial self-limited delayed puberty (DP) we have demonstrated mutations in IGSF10 leading to mis-regulation of the embryonic migration of GnRH neurons (Howard et al, EMBO MM 2016). We aimed to discover novel genetic mutations in pathways regulating GnRH neuronal migration and developme...

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 i...

Young people presenting with delay in pubertal onset or progression may have one of a spectrum of conditions, with different underlying pathological mechanisms. Whilst environmental factors such as nutrition and emotional well-being can influence the timing of puberty, in the majority of patients presenting with significantly delayed puberty there is a clear family history of delayed or arrested puberty. Pubertal timing is known to be a trait with strong heritability, demonstr...

Introduction: Delayed puberty (DP), affecting over 2% of adolescents, is defined as pubertal onset 2-2.5 SDs later than the general population. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic and genotypic discre...

Background: Polycystic ovary syndrome (PCOS) continues to be a diagnostic challenge in adolescent girls. Symptoms like oligomenorrhea and acne, and polycystic ovarian morphology on ultrasound can be normal variants in adolescents. In addition to diagnostic difficulties, there is lack of randomized controlled trials for PCOS treatments specific to adolescents. Current guidelines for diagnosis and management of PCOS in adolescents have large variations and rely ...

Background: Early recognition and treatment of cystic fibrosis related diabetes (CFRD) significantly improves respiratory and nutritional status of patients with cystic fibrosis (CF). American Diabetes Association (ADA) guidelines recommend annual screening with oral glucose tolerance test (OGTT) for all affected children from age 10 years.Objective and hypothesis: We sought to determine if screening for CFRD was optimal and to determine if early treatme...

Background: Self-limited delayed puberty (DP) often segregates in an autosomal dominant pattern, suggesting that inheritance is conferred by a small number of genes. However, the underlying genetic background is mostly unknown. By comparison, many genes have been identified where loss-of-function mutations lead to hypogonadotropic hypogonadism (HH). Despite likely overlap between the pathophysiology of delayed puberty and conditions of GnRH deficiency, few studies have examine...

During development, gonadotropin releasing hormone (GnRH) neurons are born in the nasal placode and migrate to the hypothalamus, where they position to regulate sexual reproduction by pulsatile release of GnRH. Defective GnRH neuron development or action may lead to GnRH deficiency (GD) which is characterized by absent or delayed puberty. Several GD causative genes have been identified so far, but half of the cases are still idiopathic. The employment of complementary research...

Background: Daily recombinant human growth hormone (rhGH) has been utilized since 1985 and has been proven to increase height velocity and improve body composition in growth hormone deficiency, various genetic syndromes and chronic kidney disease. Safety and efficacy are well established. Long-acting growth hormone (LAGH) analogs have been developed to improve compliance and patient experience. There are several LAGH preparations in development or early commer...