Endocrine Abstracts

The hypothalamic-pituitary-gonadal (HPG) axis is a dynamic endocrine axis, with three main periods of activity - in foetal life, during mini-puberty, and then from puberty into adult reproductive life. Between these periods the axis is dormant and thus difficult to assess, especially in mid-childhood. Inhibin B and anti-Mullerian hormone (AMH) are both markers of gonadal function - of Sertoli cells of the testes and granulosa cells of the ovary - and are very useful investigat...

The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes including short stature, reduced bone mineral density and compromised psychosocial health. Self-limited delayed puberty (DP) is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Usin...

The genetic control of puberty remains an important but mostly unanswered question. Late pubertal timing affects over 2% of adolescents and is associated with adverse health outcomes including short stature, reduced bone mineral density and compromised psychosocial health. Self-limited delayed puberty (DP) is a highly heritable trait, which often segregates in an autosomal dominant pattern; however, its neuroendocrine pathophysiology and genetic regulation remain unclear. Usin...

Whilst the timing of pubertal onset varies within and between different populations, it is a highly heritable trait. The timing of sexual maturation is highly correlated within families and in twin studies, suggesting strong genetic determinants. However, despite this strong heritability, our knowledge of the genetic control of puberty remains limited. Disturbances of puberty (precocious, delayed or arrested) encompass an important group of pathologies. Firstly, they are commo...

Background: We aim to investigate the influence of GH on pubertal growth in children receiving GH replacement therapy for GH deficiency.Methods: We analyse a large dataset of children (n=236) with GH deficiency from the international KIGS database. We examine the relationship between pubertal growth and treatment with GH replacement therapy using linear regression and repeated measures analysis, and the incremental cost benefit of increasing doses...

Gonadotropin-releasing hormone (GnRH) is the master hormone regulating the reproductive axis and its pulsatile secretion is crucial for puberty onset and fertility. Disruption in GnRH neuron development or hypothalamic function can lead to absent or delayed puberty (DP) due to GnRH deficiency, with a phenotypic spectrum from severe delayed puberty to partial or complete Hypogonadotropic Hypogonadism (HH). HH can also be present as a shared trait with other neurodevelopmental d...

Introduction: Delayed puberty (DP), affecting over 2% of adolescents, is defined as pubertal onset at 2-2.5 SDs later than the general population. Two common underlying aetiologies are self-limited DP (SLDP) and congenital hypogonadotrophic hypogonadism (HH). However, these can be difficult to discern between on first presentation of a patient to endocrinology services. This study sought to elucidate phenotypic and genotypic differences between the two diagnoses in order to op...

Context: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is a rare endocrine disease in which patients have isolated gonadotropin releasing hormone (GnRH) deficiency in the context of otherwise normal structure and function of anterior pituitary and hypothalamus with normal olfactory ability.Objective: To explore the underlying pathogenic defect in patients with delayed puberty.Patients: We investigated genetic defects in...

Background: PTEN hamartoma tumour syndrome (PHTS) is a rare autosomal dominant disorder characterised by macrocephaly and multiple hamartomas. It carries an increased risk of several cancers, including breast, thyroid and endometrium. PHTS is caused by inactivating mutations of PTEN (phosphate and tensin homologue deleted on chromosome 10), which encodes a tumour suppressor phosphatase. Published guidelines for surveillance are available for adult patients but not adv...

Background: PTEN hamartoma tumour syndromes (PHTS) are rare autosomal dominant inherited disorders characterised by macrocephaly, multiple hamartomas and an increased risk of several cancers, including breast, thyroid and endometrium. PTEN encodes a tumour suppressor phosphatase that regulates cell survival and migration. Published guidelines are available for adult patients but screening in children is currently not standardised. Moreover, there is poor genotype-phenotype cor...