Endocrine Abstracts

Intratumoural hypoxia is associated with aggressive and metastatic phenotypes with poor prognosis. The transcription factor HIF-1α is a key regulator of hypoxia-mediated gene expression that is documented to promote tumour growth and metastasis in a wide range of cancers. However its role in the development of thyroid carcinomas is relatively unknown. We have previously shown that HIF-1α is highly active in a range of thyroid cancer cell lines with highest activity o...

Objective: The diagnosis of subclinical Cushing’s syndrome in patients with incidentalomas is not always straight forward and a number of different criteria have been used. The 1 mg overnight dexamethasone suppression test has been recommended as a screening test, followed up by other tests of the hypothalomo–pituitary–adrenal axis to confirm the diagnosis. In this study we investigate whether the low-dose dexamethasone suppression test offers additional informa...

Background: Intratumoural hypoxia is associated with an aggressive and metastatic phenotype and poor prognosis. The transcription factor Hypoxia-inducible Factor-1α (HIF-1α) is a key regulator of hypoxia, inducing the expression of genes which promote tumour cell survival, such as carbonic-anhydrase IX (CA-IX) playing a role in cell adhesion, pH regulation and dedifferentiation of the tumours. Here we investigated whether there is cross talk between the HIF-1 and Wnt...

Background: Mutations in the UMOD gene, which encodes the Tamm-Horsfall Glycoprotein (THP), cause FJHN, an autosomal dominant disorder characterised by gout and renal failure. THP is a 640 amino acid glycosylphosphatidylinositol-anchored protein, containing three Epidermal Growth Factor (EGF)-like domains, a cysteine-rich region and a Zona Pelllucida (ZP) domain. THP is translated into the Endoplasmic Reticulum (ER) lumen, glycosylated in the Golgi apparatus, trafficked...

Background: Tissue hypoxia is a hallmark of rapidly proliferating tumours which most frequently adapt and prosper under low oxygen tension. The transcription factor, HIF-1α, is mediating these effects and induces target genes involved in survival, invasion and resistance to drugs and radiation. No data are available on the functional regulation of HIF-1α in thyroid carcinoma cells.Methods: Using thyroid carcinoma cells derived from papillary (N...

Thyroid dysfunction is not uncommon in pregnancy and is associated with various maternal, foetal and neonatal complications. We report the occurrence of neonatal hyperthyroidism in two successive pregnancies in a post radio-ablation mother with Graves’ disease who is on thyroxine replacement.Mother: A 30-year-old lady, treated for Graves’ thyrotoxicosis with radioiodine 10 years ago, was on thyroxine 100 mcg replacement for hypothyroidism. She ...

T3 is essential for skeletal development and T3-actions in bone are mediated mainly by the nuclear receptor TRα1. We previously identified that FGFR1 is a T3-responsive gene in osteoblasts by subtraction hybridization. In mice that harbor a dominant negative mutation PV, FGFR1 mRNA expression is reduced in TRα1PV mutants that exhibit skeletal hypothyroidism and increased in TRβPV/PV mice with skeletal thyrotoxicosis. In this study, primary ...

T3 is essential for skeletal development and its actions are mediated by two nuclear receptors (TRs), with TR alpha (TRa) being functionally predominant in bone. The TRa1 isoform binds T3 with high affinity and activates target gene expression in response to hormone. TRa2, however, does not bind T3 or regulate transcription in response to hormone. Intriguingly, TRa2 is expressed at high levels from early in development in all tissues and is conserved in all mammals, although i...

Prostaglandin F2a (PGF) receptor (FP) expression is up-regulated in neoplastic epithelial and perivascular cells in endometrial adenocarcinomas, indicating potential regulation of vascular function by PGF via the FP receptor. This study investigated the potential role of PGF-FP receptor signalling in modulating vascular function in endometrial adenocarcinomas.Endometrial biopsies were obtained in accordance with Ethics Committee guidance with ...

A 67 year old man with 1 month history of malaise was referred when his thyroid profile suggested secondary hypothyroidism with a fT4 of 4.9 picomoles per litre, fT3 3.4 picomoles per litre and TSH 0.03 milli units per litre. Physical signs were unremarkable. Investigations:- cortisol (random) 294 nanomols per litre, prolactin 960 micro units per millilitre, testosterone < 0.04 nanomols per litre, FSH 5.2 units per litre, LH 0.07 units per litre and IGF-1 17.7 nanomols per ...