Endocrine Abstracts

OPUS is a population-based prospective cohort study of post-menopausal women from five European cities. We investigated whether TSH, fT4 and fT3 are associated with fracture risk, bone mineral density (BMD) at hip and spine, bone formation (osteocalcin, procollagen type 1 N-terminal propeptide), bone resorption (N- and C-telopeptides of type 1 collagen, NTX, CTX), pulse rate, grip strength and balance. Vertebral fractures were determined at baseline and 6 years follow-up. Usin...

Congenital hypothyroidism (CH), occurs with a frequency of one in 3–4000 and is most commonly due (85%) to complete or partial failure of thyroid gland development (dysgenesis). Several transcription factors (TTF-1/Nkx2.1, TTF-2/FOXE1, PAX-8), are highly expressed in the developing rodent thyroid. We first showed that the FKHL15 gene is the human homologue of TTF-2, identifying a homozygous, loss-of-function, mutation in two siblings with CH, thyroid agenesis, clef...

Introduction: Subclinical hypothyroidism (SCH) is recognised as an increased risk for cardiovascular disease (CVD). Low number of circulating endothelial progenitor cells (EPC), defined as mononuclear cells, expressing endothelial (vascular endothelial growth factor receptor, VEGFR-2) and stem cell (CD-34, CD-133) markers is associated with CVD. Our aim was to identify whether reduced EPC number might contribute to increased CV risk in subclinical and overt hypothyroidism (Hy)...

The prohormone T4 represents the majority of circulating thyroid hormones, whereas 80% of the active hormone T3 is derived from T4 by the actions of the type 1 and type 2 deiodinase enzymes (D1 and D2). Local generation of T3 by D2 regulates ligand supply to the nuclear T3-receptor in pituitary, brown adipose tissue and brain, and this enzyme is also expressed in bone. Hypothyroidism in children causes delayed bone age and growth retardation, whereas thyrotoxicosis in adults c...

Endocrine cells utilise endocytosis to scavenge polypeptide hormones, and to generate signals from inactive precursors, such as release of thyroid hormones from thyroglobulin in thyrocytes, and activation of vitamin D after reabsorption of ultrafiltrated pro-vitamin D binding protein complex by renal proximal tubular cells (PTC). We have investigated the role of CLC-5, a chloride/proton antiporter expressed in apical endosomes and the apical plasma membrane of thyrocytes and P...

The TEARS database links six datasets for patients with treated and stabilised thyroid conditions. It has been validated previously and represents a population-based patient sample, as patient identification includes using regional-wide biochemical records and prescription data. For patients on long-term thyroxine we examined the outcome of ‘serious vascular events’ defined as vascular death, non-fatal myocardial infarction and non-fatal stroke as used in the Anti -t...

Context: HIF-1α is frequently upregulated in many tumour types and has been shown to be critical for radio- and chemosensitivity in pre-clinical studies. However the regulation and function of HIF-1α is unknown in thyroid carcinomas.Objectives: Here, we evaluated basal expression and regulation of HIF-1α and target genes in primary thyroid carcinomas and in thyroid cancer cell lines (NPA, FTC-133, ARO).Design and out...

Hypothyroidism causes delayed ossification and growth retardation. T3 stimulates hypertrophic chondrocyte differentiation whereas unliganded T3 receptors (TRs) repress gene expression and maintain cell proliferation in the absence of hormone. During development the type 3 deiodinase enzyme (D3) inactivates thyroid hormones and prevents T3-access to the fetus. At birth diminishing D3 activity and increasing T3 availability triggers the onset of cell differentiation and correlat...