Endocrine Abstracts

Childhood hypothyroidism results in severely delayed skeletal development whereas adult thyrotoxicosis is associated with a 3–4 fold increase in osteoporotic fracture. To investigate molecular mechanisms underlying these abnormalities we characterized the skeletal phenotypes of mice harboring dominant negative mutations (TRα1PV/+, TRα1R384C/+, TRβPV/PV) or deletions (TRα0/0, TRβ−/−) of the genes encoding TRα and TRβ. Endochon...

Alternative splicing of the rat THRB gene produces thyroid hormone (T3) receptor (TR) beta isoforms 1-3 and also TRdeltabeta3, which lacks the DNA binding domain but binds T3. TRbeta1 is ubiquitous; TRbeta2 is found predominantly in pituitary and hypothalamus, whilst TRbeta3 and TRdeltabeta3 are expressed widely in a ratio that is tissue-specific and T3-dependent. We investigated the function of the newly identified TRbeta3 and TRdeltabeta3 isoforms by transient transfection a...

Background: Anaplastic thyroid-carcinomas (ATC) and a subset of papillary (PTC) and follicular (FTC) thyroid carcinomas behave aggressively showing metastatic spread and radio-resistance. Both the PI3K and HIF pathways are associated with aggressiveness and metastasis in thyroid carcinoma.Aims: To assess if the PI3K/HIF pathways contribute to radio-resistance and assess the effect of PI3K/HIF inhibition on radio-sensitivity of thyroid-carcinoma cells (85...

Background: Anaplastic thyroid-carcinomas (ATC) and a subset of papillary (PTC) and follicular (FTC) thyroid carcinomas behave aggressively showing metastatic spread and radio-resistance. Both the PI3K and HIF pathways are associated with aggressiveness and metastasis in thyroid carcinoma.Aims: To assess if the PI3K/HIF pathways contribute to radio-resistance and assess the effect of PI3K/HIF inhibition on radio-sensitivity and metastatic behaviour of th...

Thyroid hormones stimulate bone formation and linear growth in children. Paradoxically, childhood thyrotoxicosis causes short stature and craniosynostosis due to early closure of the growth plates and skull sutures. In adults, however, thyroid hormone excess increases bone turnover and results in progressive bone loss and osteoporosis. Activating mutations of fibroblast growth factor receptor-3 (FGFR3) cause achondroplastic dwarfism and we have shown that T3 augments FGFR sign...

Patterns of food consumption have a profound influence on hormone rhythmicity and fat storage, but until now only crude manipulations of food availability have been possible in rodents. We have used a CLAMS-based system in conjunction with automated serial blood sampling to investigate the effect of continuous feeding on ghrelin secretion and adiposity. Six-week old male Sprague–Dawley rats (n=6) were housed in metabolic cages and ad-libitum fed with standar...

Recent controversial studies in mice imply that TSH inhibits bone remodelling, suggesting TSH-deficiency rather than thyroid hormone excess causes bone loss in thyrotoxicosis. Measurement of the TRH-stimulated rise in TSH following three days administration of graded doses of T3 is the gold-standard for determining resistance to thyroid hormone (RTH). During this test, T3 excess coupled with suppressed TSH should induce high bone turnover, whilst administration of TRH causes a...

Background: Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension, usually diagnosed by adrenal vein sampling (AVS) or computed tomography (CT). We compared the outcomes of patients diagnosed by CT and AVS and determined if CT can reliably diagnose unilateral primary aldosteronism in young patients with an evident phenotype.Methods: Patient data were obtained from 18 internationally distributed centres ...

Background: In the UK, Growth Hormone (GH) is indicated for treatment of children with short stature secondary to growth hormone deficiency (GHD), Prader Willi syndrome (PWS), Turner syndrome (TS), SHOX gene mutation, chronic renal insufficiency and born small for gestational age (SGA).Objectives: The aim was to assess the compliance of our local practice with the NICE guidance for GH therapy in children in addition to local guidance that TFTs and IGF-I ...

We work in a service at UCLH in London which cares for young people and adults with differences of sex development. Among other diagnoses CAH makes up quite a lot of our cohort of patients. Adolescents with CAH that our team see include those born with atypical genitalia who may have had, or have not had surgery in childhood on their clitoris or vagina. We also see adolescents with CAH who have issues with puberty and their periods. For adolescents with issues with their genit...