Endocrine Abstracts

A 44-year-old woman presented to an emergency department with ear pain and worsening of longstanding headache. There was no history of menstrual disturbance, galactorrhoea, tiredness or weight gain and physical examination demonstrated only a left homonymous hemianopia. CT head scan revealed a brightly enhancing, enormous, lobulated mass arising from the pituitary fossa and causing obstructive hydrocephalus through compression of the fourth ventricle. Following collection of b...

Objective: To determine whether transdermal oestrogen (E2) preparations alter total cortisol and cortisol binding globulin (CBG) concentration similarly to oral E2 treatment.Methods: This cross-sectional, observational study compared levels of total serum cortisol, CBG, the free cortisol index (FCI) and salivary cortisol levels (as a measure of free cortisol) in oestrogen naïve women (n=15), women taking oral oestrogen (...

Background: Aberrations in the timing of puberty may result in significant adverse health outcomes, including cancers, cardiovascular and neurological pathologies. Self-limited delayed puberty (DP) (i.e. constitutional delay of puberty) runs in families with either autosomal dominant or complex inheritance patterns in >70% of families, indicating a strong genetic basis of the trait. However, only a few genes have been identified underlying DP so far....

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...

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...

Diazoxide is an agonist of ATP sensitive K+ (KATP) channels in beta-cells and is used in the treatment of hyperinsulinism caused by insulinomas or Hyperinsulinism in Infancy (HI). The responsiveness of patients to diazoxide is highly variable and complicated by side-effects which include hypertension and hypertrichosis. The aim of this study was to examine the actions of a novel benzothiadiazine-derivative, BPDZ-154, on beta-cell KATP channels and insulin release. W...

BackgroundCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder characterized by insufficient cortisol production resulting in excess adrenocorticotropic hormone (ACTH) and adrenal androgen production. Standard-of-care therapy with glucocorticoids (GC) is suboptimal due to the difficulty of balancing control of the ACTH-driven androgen excess against the serious long-term side effects associated...

Background: The initiation of puberty is heralded by increasing gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. During embryonic life the GnRH neuroendocrine network develops thanks to a coordinated migration of neurons from the nasal placode to the forebrain. Our group has previously demonstrated that dysregulation in GnRH neuronal migration leads to delayed pubertal onset. Late puberty affects up to 2% of the population and is associated with adverse h...

Background: Self-limited DP often segregates in an autosomal dominant pattern, but in the majority of patients the neuroendocrine pathophysiology and its genetic regulation remain unclear. By comparison, many genes have been identified where loss-of-function mutations lead to IHH. Despite likely overlap between the pathophysiology of DP and conditions of GnRH deficiency, few studies have examined the contribution of mutations in IHH genes to the phenotype of DP.<p class="a...

Triple A syndrome (AAAS) is a rare, incurable, homozygous disorder, characterised by tissue-specific degeneration resulting in adrenal failure and neurodisability. The AAAS gene encodes ALADIN, a nuclear pore complex (NPC) protein necessary for nuclear import of DNA protective molecules, important for redox homeostasis. ALADIN’s role is not fully characterised: its discovery at the centrosome and the endoplasmic reticulum suggests a role outside the NPC. The inte...