Endocrine Abstracts

Next Generation Sequencing (NGS) is becoming widely used for genetic diagnosis. While its capacity for detection of human genetic variations (GV) is outstanding, drawbacks is the identification of numerous GV of which functional significance cannot be predicted in silico by computer programs (variants of uncertain significance, VUS). Currently, only sensitive (but also expensive and time-demanding) in vitro cell assays, can trustfully ascertain pathogenicity ...

The main product of the thyroid gland, T4, is a prohormone. 5’-deiodination is needed to convert T4 into the active, nuclear receptor-binding hormone, T3. Pharmacological modulation of activating 5’-and inactivating 5-deiodination of iodothyronines would be desirable in a number of medical conditions, including hypothyroidism, hyperthyroidism and various cancers. A structural and mechanistic understanding of deiodinase (DIO) catalysis...

The incidence of thyroid cancer is rapidly increasing worldwide. Whilst outcome in thyroid cancer is generally good, up to 25% of patients develop recurrence, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver events. Whole exome sequencing data were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatic analysis of data on N=43 patients whose tumours recurred was ...

Introduction: Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with barely normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia, growth retardation, constipation, dyspraxia and intellectual deficit. Hormonal assessment often shows decreased/low-normal free thyroxine (fT4) and increased/high-normal free triiodothyronine (fT3) concentrations, resulting in a low fT4/fT3 ratio, w...

Hypothyroidism refers to a thyroid hormone (TH) deficiency which mainly affects women (10/1 ratio). The higher default incidence in women remains unexplained. Diagnosis of hypothyroidism is based on a single thyroid-stimulating-hormone (TSH) measurement albeit TSH secretion displays pulsatile patterns which are under the positive control of hypothalamic thyrotropin-releasing-hormone (TRH) and negative feedback exerted by THs. Pituitary thyrotrophs form the smallest (2-4%) pitu...