Searchable abstracts of presentations at key conferences in endocrinology

ea0081ep870 | Reproductive and Developmental Endocrinology | ECE2022

Combined omic analysis revealed autism-linked NLGN3as new candidate gene associated to GnRH neuron development and disease

Oleari Roberto , Lettieri Antonella , J.J. Paganoni Alyssa , Amoruso Federica , Scheiffele Peter , Howard Sasha , Cariboni Anna

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...

ea0085oc5.3 | Oral Communications 5 | BSPED2022

UK protocol for induction of puberty with gonadotropins in males with hypogonadotropic hypogonadism

Dunkel Leo , Prasad Rathi , Martin Lee , Senniappan Senthil , Butler Gary , Howard Sasha

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...

ea0090p715 | Reproductive and Developmental Endocrinology | ECE2023

A systematic review of gonadotropin and GnRH therapy for the induction or completion of puberty in males with hypogonadotropic hypogonadism

Alexander Emma , Faruqi Duaa , Farquhar Robert , Unadkat Ayesha , Ng Yin Kyla , Kokotsis Vasilis , Howard Sasha

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...

ea0066p20 | Diabetes 1 | BSPED2019

Identifying barriers and solutions to the optimal management of a patient with T1DM and a severe life limiting dermatological condition

Wijesinghe Nimasha , Drew Samantha , Cunjamalay Annaruby , Howard Sasha R , Amin Rakesh , Peters Catherine

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...

ea0058oc4.5 | Oral Communications 4 | BSPED2018

Delayed or Absent? – use of next generation sequencing diagnostic tools in a UK puberty cohort

Howard Sasha R , Cabrera Claudia P , Barnes Michael R , Dunkel Leo

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...

ea0033oc1.5 | Oral Communications 1 | BSPED2013

Novel genes affecting the timing of puberty

Howard Sasha , Storr Helen , Metherell Lou , Barnes Michael , Cabrera Claudia , Gausti Leonardo , Wehkalampi Karoliina , Dunkel Leo

Background: Disturbances of pubertal timing affect >4% of the population and are associated with adverse health outcomes. Studies estimate 60–80% of variation in pubertal onset is genetically determined, but few genetic factors are known. We hypothesise that causal variants will be low-frequency, intermediate-impact variants and will be enriched in populations at the extremes of normal pubertal timing. Families with constitutional delay in growth and puberty (CDGP) ha...

ea0031p145 | Growth and development | SFEBES2013

Familial constitutional delay in growth and puberty is a condition with significant genetic heterogeneity and limited overlap with the timing of puberty in the general population

Howard Sasha , Barnes Michael , Storr Helen , Wehkalampi Karoliina , Metherell Lou , Dunkel Leo

Background: Pubertal timing has importance both for the individual, but also for public health. Previous studies estimate that 60–80% of variation in pubertal onset is genetically determined. Recently, a large genome-wide association study (GWAS) meta-analysis identified 42 loci for age-at-menarche (AAM), which explained 3.6–6.1% of the variation in the general population, but causal genes have not been identified.CDGP is defined as pubertal on...

ea0094op1.1 | Neuroendocrinology and Pituitary | SFEBES2023

Gene methylation status contributes to delayed puberty

Hall Charlotte L , Brempou Dimitria , Oakey Rebecca J. , Howard Sasha R.

Self-limited delayed puberty is a condition that is frequently familial with strong genetic determinants. It has been linked to coding region sequence variation by next generation sequencing of affected individuals, identifying genetic regulation of gonadotropin-releasing hormone (GnRH) pathways underlying this condition. However, the role of epigenetic modifiers of human pubertal timing is underexplored. The Hypothalamic-pituitary-gonadal (HPG) axis is unique as it is active ...

ea0095oc3.1 | Oral Communications 3 | BSPED2023

The first description of an MC4R variant in a patient with Kallmann syndrome and obesity

A Aslam Aisha , Lim Sharon , Willemsen Ruben , R Howard Sasha , Gevers Evelien

Introduction: Pathogenic MC4R variants result in hyperphagia and early onset obesity but puberty is not usually affected. We describe an MC4R variant in a patient with Kallmann syndrome and obesity.Case: A 16 year old male with repaired Tetralogy of Fallot, anosmia, autism and anxiety, was referred with obesity and delayed puberty. Height was -1.31 SDS, BMI 30.7 kg/m2. He had a high arched palate, normal skin, normal hai...

ea0095p40 | Gonadal, DSD and Reproduction 1 | BSPED2023

Systematic review and meta-analysis of spermatogenesis rates after pubertal induction with gonadotropins in males with hypogonadotropic hypogonadism

Alexander Emma , Yin Kyla Ng , Faruqi Duaa , Farquhar Robert , Unadkat Ayesha , Varughese Rachel , Howard Sasha

Background: 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 stimulates Sertoli and Leydig cells directly, leading to increased testicular...