Endocrine Abstracts

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 ...

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...

FGFs and T3 are required for skeletal development. Activating mutations of FGF receptor-1 (FGFR-1) and FGFR-2 cause craniosynostosis, whilst FGFR-3 is a negative regulator of chondrocyte proliferation and activating mutations cause achondroplasia. Childhood hypothyroidism causes delayed ossification and growth retardation, whereas thyrotoxicosis accelerates bone development, induces premature growth plate and skull suture closure and causes short stature and craniosynostosis. ...

T3 and fibroblast growth factors (FGFs) are critical regulators of chondrocyte proliferation during bone formation and we identified recently that T3 modulates skeletal FGF receptor-1 (FGFR1) activity. FGFRs signal via several routes including mitogen-activated protein kinase (MAPK), STAT and phospholipase C gamma pathways. Mechanisms determining which pathways are activated by FGFRs are poorly understood but include alternative splicing of exons encoding variable domains with...

In humans only thyroid hormone (T3) receptor (TR) beta1 and beta2 mRNAs have been identified, whereas alternative splicing generates recently characterised beta3 and deltabeta3 transcripts in rat and further N-terminal isoforms in other species. We investigated whether additional transcripts arise from the human TRbeta gene by 5'-RACE. Five distinct TRbeta1 transcripts were isolated, including the previously described TRbeta1 mRNA and four novel 5'-untranslated region (5'-UTR)...

A 53 year old man with ANCA-positive glomerulonephritis was referred with a 3-month history of hypercalcaemia. There was no significant family history and treatment consisted of Maxepa concentrated fish oils 5g/day for glomerulonephritis and lansoprazole plus Bisodol (proprietary indigestion preparation containing calcium, magnesium and sodium bicarbonate) for a hiatus hernia. Investigations revealed a corrected calcium concentration of 3.06 mmol/l, phosphate 1.27 mmol/l, crea...

Plasma homocysteine is now regarded as a graded risk factor for vascular disease comparable to smoking, high cholesterol and raised blood pressure. In diabetes homocysteine values have correlated with microalbuminuria and are thought to contribute to vascular damage. Folic acid is an essential co-factor for homocysteine metabolism and folic acid supplementation has been shown to reduce plasma homocysteine by about 30%.In this study patients with Type II ...

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 individuals. Rapid detection by neonatal screening and T4 administration is essential to prevent severe mental retardation and impaired growth. About one third of CH is due to mutations in known genes including the thyrotropin receptor (TSHR).Two Welsh male siblings with CH were detected, both had normally sized and located thyroid glands, no iodide uptake and were negative for thyroid bloc...

Background: Lipocalin 2 (NGAL) is considered a pro-inflammatory adipokine. Noting the conflicting reports as to the role of Lipocalin 2 in metabolic disease, it remains unclear whether an acute or chronic state affects its impact on adipocyte function. In an attempt to address this our current studies investigated for the first time in humans, whether Lipocalin 2 in abdominal subcutaneous adipose tissue (AT) may influence mitochondrial function and browning of adipocytes, as c...