Endocrine Abstracts

Glucocorticoids are by far the most effective anti-inflammatory therapy for asthma (and many other inflammatory diseases). Glucocorticoids bind to glucocorticoid receptors in the cytoplasm and translocate to the nucleus, where they interact as dimers with glucocorticoid response elements in the promoter region of steroid-sensitive genes to switch on transcription of anti-inflammatory genes, (such as MKP-1). This involves binding of GR to coactivator proteins and acetylation of...

Armour thyroid (Armour) is unlicensed in the UK for the treatment of hypothyroidism. It is natural porcine-derived thyroid replacement with 1 grain containing 38 mcg levothyroxine (T4) and 9 mcg L-triiodothyronine (T3), and unspecified amounts of T1, T2 and calcitonin. We have used Armour as a third line agent in selected patients who have not responded adequately to T4 monotherapy, and combination T4/T3 therapy since 2003.Aim: To assess c...

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...

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....

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...

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...

Hyperinsulinism in Infancy (HI) is the most common cause of recurrent or persistent hypoglycaemia in early childhood, and manifests as either diffuse abnormalities of pancreatic beta-cell function (Di-HI), or focal adenomatous hyperplasia of beta-cells (Fo-HI). Di-HI is caused by defects in KATP channel genes ABCC8 (SUR1) or KCNJ11 (Kir6.2). Fo-HI arises from somatic loss of maternal heterozygosity resulting in the expression of paternally-derived mutation(s) in SUR1 or Kir6.2...