Endocrine Abstracts

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: Elevated parathyroid hormone (PTH) levels are associated with increased cardiovascular diseases (CVD) in the patients with impaired kidney function. We aimed to investigate whether PTH levels are associated with CVD in persons without significant renal diseases.Methods: This is a cross-sectional study and we included 1951 Korean subjects aged ≥30 years (men 46.6%), who underwent 64-slice multidetector-row cardiac computed tomography (...

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: Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individua...

Background: 5α-Reductase type 2 deficiency (5ARD) is caused by mutations in the SRD5A2 gene. Inadequate masculinisation in XY individuals results from failure to convert testosterone (T) to dihydrotestosterone (DHT), a potent androgen. A decreased serum T:DHT ratio is frequently taken to identify 5ARD, but requires hCG stimulation for prepubertal patients; findings are not always supported by genotyping. Urine steroid profiling (USP) by GC-MS is established as showing sig...

The plasma membrane thyroid hormone (TH) transporter, MCT8, is present in the human placenta from early gestation and is postulated to participate in transplacental transfer of TH. In vitro, MCT8 overexpression decreases the survival of human cytotrophoblast in a TH-independent manner.Objective: To examine the role of Mct8 in fetoplacental growth using the Mct8 knockout (ko) mouse model.Methods: Heterozygous females were mat...

Thyroid hormones (THs) are important for fetal and placental development. Monocarboxylate transporters 8 and 10 (MCT8 and MCT10) are effective plasma membrane TH transporters expressed in the human placenta from 6 weeks of gestation. Both have been localized to human villous trophoblasts and extravillous trophoblasts (EVTs).Aims: Using HTR-8/SVneo cells as a model of 1st trimester EVTs, we assessed 1) T3 effects on gene expression, cell prolif...

Maternal thyroid hormones (THs) are important for fetoplacental development. We have previously reported lower fetal circulating concentration of THs in severe intrauterine growth restriction (IUGR) compared to gestationally-matched normal fetuses. The villous placental expression of TH receptors (TRs) and the TH transporter MCT8 is increased, whilst MCT10 expression is decreased, with severe IUGR.Objective: To assess the TH responsiveness of human cytot...

Thyroid hormones (TH) are important for the development of the fetus and placenta. Monocarboxylate transporter 8 (MCT8) is a potent plasma membrane TH transporter, present in the human placenta from 6 weeks of gestation. Its expression increases significantly with advancing gestational age. We postulate that MCT8 plays an important role in human placental development.Objective: To assess the effects of altered MCT8 expression on the survival, syncytialis...