Endocrine Abstracts

Puberty is a fascinating transition period in the mammalian lifespan, but the biological control of pubertal timing remains poorly understood. Developmental abnormalities of the gonadotropin-releasing hormone (GnRH) neuronal network have been shown to be responsible for disorders of pubertal timing, in a spectrum of conditions ranging from idiopathic hypogonadotropic hypogonadism (IHH) to self-limited delayed puberty. We hypothesized that important regulators of pubertal timin...

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 coh...

Key genetic contributors are recognised to underlie the phenotype of central precocious puberty (CPP), including the imprinted genes Makorin ring finger protein 3 (MKRN3) and Delta-like homolog 1 (DLK1), alongside Kisspeptin-1 (KISS1) and (KISSR1). These genes have implicated mis-regulation of transcriptional control of the kisspeptin and gonadotropin-releasing hormone (GnRH) neuroendocrine systems in onset of CPP. However, many familial cases of CPP remain without clear a gen...

Prohormone convertase 1/3 (PC1/3) deficiency is rare, caused by homozygous or compound heterozygous mutations in the PCSK1 gene. PCSK1 encodes a serine protease important in cleavage of several proneuropeptides and prohormones. Despite a variety of known endocrine associations, paediatric diabetes mellitus is rare, described only once before. Previous understanding was that biological activity of elevated proinsulin (<5% of the activity of insulin) confers protection from ...

Objectives: Abnormal pubertal timing affects >4% of adolescents and is associated with adverse health outcomes. Up to 80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority the neuroendocrine pathophysiology and genetic regulation remain unclear. Mis-regulation of the embryonic migration of GnRH neurons has been implicated in the pathogenesis of DP (Howar...

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 the pulsatile release of GnRH. Defective GnRH neuron development or action may lead to GnRH deficiency (GD) which is characterized by absent or delayed puberty (1). GD can also be present as a trait shared by several complex neurodevelopmental disorders (NDDs), such as cerebellar ataxia, developm...

Hypogonadotropic hypogonadism (HH) is a rare reproductive disorder that results in a lack of normal pubertal development and reduced potential for fertility in adult life. The condition is characterised by low circulating sex steroid concentrations resulting from a deficiency of pituitary gonadotropin production. HH may be congenital or acquired, most commonly due to tumour or treatment for malignant disease. When associated with anosmia it is termed Kallmann syndrome. HH is a...

Background and aims: Hypogonadotropic hypogonadism is characterised by inadequate secretion of gonadotropins (luteinising hormone (LH) and follicle-stimulating hormone (FSH)) leading to absent, partial or arrested puberty. In males, classical treatment with testosterone promotes virilisation but does not facilitate testicular growth or spermatogenesis. Conversely, treatment with gonadotropins or gonadotropin-releasing hormone (GnRH) stimulates Sertoli and Leydig cells directly...

Background: We present a case of a 10 year old female with T1DM, referred to our tertiary centre for complex diabetes care due to her other severe chronic dermatological condition. We discuss the difficulties with optimizing diabetes control in such a chronic debilitating condition which has a pervasive effect on T1DM treatment.Case: To our knowledge this is only the second reported case of a child with T1DM and Epidermolysis Bullosa. Severe Recessive Dy...

Objectives: Several different pathogenic mechanisms may converge on a final common pathway to produce the phenotype of delayed pubertal timing. Abnormal pubertal timing affects >4% of adolescents and is associated with adverse health outcomes. Up to 80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority the neuroendocrine pathophysiology and genetic regul...