Endocrine Abstracts

Background: Down Syndrome (DS) is the commonest form of chromosomal trisomy. Genetic factors in DS may increase the risk for diabetes. Obesity and type 2 diabetes mellitus (T2DM) rates have increased in the general populationbut it is not known whether this similarly affected people with DS.Objective: To determine whether DS is associated with increased incidence of diabetes and the relationship with obesity across the lifespan compared to controls.<...

Background: Primary adrenal insufficiency (PAI) is a rare, genetically heterogenous condition, characterised by hypocortisolaemia and high plasma ACTH levels in the presence or absence of mineralocorticoid deficiency. PAI can be life-threatening if unrecognised, misdiagnosed or under/untreated. Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive form of PAI characterised by isolated glucocorticoid insufficiency. Mutations in the MC2R/ACTH receptor, ...

Mutations in CYP11A1, like those in STAR cause lipoid congenital adrenal hyperplasia manifesting with adrenal and gonadal insufficiencies along with derangements of the renin/angiotensin system. Increased adrenal size is usually a feature of STAR but not of CYP11A1 mutation. Milder forms presenting without all of these features have also been described. We present six patients from four families with CYP11A1 mutations discovered by ...

Introduction: In recent years a growing number of gene mutations have been identified which cause a myriad of syndromes having adrenal insufficiency as a core characteristic. The evolution of each syndrome is dependent on the variant and the particular gene affected. Common practice is for candidate genes to be sequenced individually, which can be time consuming and is complicated by overlapping clinical phenotypes. The increasing availability and cost effectiveness of whole e...

Familial glucocorticoid deficiency (FGD, OMIM#202200) is a rare autosomal recessive disorder characterised by adrenal resistance to the action of ACTH, with isolated glucocorticoid deficiency. Recently, mutations in NNT, encoding the mitochondrial anti-oxidant nicotinamide nucleotide transhydrogenase have been reported to cause FGD.Our index case, from a highly consanguineous Kashmiri family, was diagnosed with adrenal insufficiency during a sep...

Background: The identification of MRAP in 2005 as the first melanocortin-2-receptor (MC2R)/ACTH receptor accessory protein provided insight into the regulation of the melanocortin receptor system. Mutations in MRAP cause Familial glucocorticoid deficiency, an autosomal recessive disorder resulting in isolated cortisol deficiency. In vitro studies showed that MRAP was essential for the functional expression of the MC2R. The melanocortin receptor (MCR) family (MC1R to MC5...

Background: The hypothalamus-pituitary-adrenal axis (HPA) controls the neuroendocrine response to psychological and physiological stress. The balance of the hormones synthesised and secreted by these organs is tightly regulated. However, there are intrinsic differences in the relative expression of these hormones depending on sex, which can influence the magnitude of the endocrine response to stressors or the response to pharmacological treatments. Herein, we ...

Background: Thyroid hormones are essential for the adequate growth and development of the kidney and also target changes in glomerular and tubular functions and electrolyte and water homeostasis. Hyperthyroidism leads to an increase in glomerular filtration rate (GFR) and renal blood flow with converse effects seen in hypothyroidism. In turn, the kidneys are responsible for the metabolism and elimination of thyroid hormones and thus renal disease can lead to s...

Background: Childhood obesity is the single most pressing public health emergency of the 21st century. The prevalence has increased at alarming rates and globally over 41 million children under 5 years of age are classified as overweight/obese. Overweight and obese children are likely to stay obese as adults and develop multi-morbidities including type 2 diabetes, cancer, non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease at an earlier age. The ava...

Background: Congenital isolated ACTH deficiency (IAD) is a rare condition characterised by low plasma ACTH and serum cortisol with normal production of other pituitary hormones. TBX19 is a T-box pituitary restricted transcription factor important for POMC gene transcription and terminal differentiation of POMC-expressing cells. TBX19 gene mutations have been shown to cause neonatal-onset congenital IAD. To date 25 mutations in TBX19 have been described, five ...