Endocrine Abstracts

Thyroid hormone (T3) is essential for skeletal development and maintenance of bone mineralisation. T3 actions are mediated by two receptors, TRalpha and TRbeta. Mutations in TRbeta cause autosomal dominant resistance to thyroid hormone (RTH) due to dominant negative activity of the mutant receptor. Short stature and abnormal skeletal development are prominent features of RTH, whereas TRalpha mutations have not been described and are postulated to result in no phenotype or to b...

The generation of a knockout mouse lacking all POMC-derived peptides by Yaswen et al provided further support for the importance of the melanocortin system in regulating body weight. POMC-null mice have a greater food intake than wild-type littermates on both low fat and high fat diets, resulting in increased body weight. In addition to obesity, these mice have altered pigmentation and defective adrenal development.The hypothalamo-pituitary-thyroid axis (HPT) in the...

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)...

Radioidine (RI) has been implicated as an adverse factor causing deterioration of Thyroid-Associated Ophthalmopathy (TAO). Oral steroids administered after RI appear to protect patients' eyes, and this practice is now widespread. Two factors may confound the controversy surrounding the effects of RI on TAO. Firstly hypothyroidism, which is common after RI and is independently detrimental to the eyes, and secondly studying patients who are in different phases of the natural his...

The prognosis of differentiated thyroid cancers is influenced by their ability to accumulate iodine and hence their sensitivity to ablative 131I therapy. Radioiodine concentration is mediated by the sodium-iodide symporter (NIS). We have previously identified PTTG and fibroblast growth factor-2 (FGF-2) as potential prognostic indicators for differentiated thyroid cancers. Furthermore, we demonstrated that FGF-2 reduces iodide uptake in FRTL5 cells and primary human ...

Calcium sensing receptor (CaSR) mutations may result in either hypocalciuric hypercalcaemia or hypocalcaemic hypercalciuria due to a loss or gain of function, respectively. It has also been postulated that some gain of function CaSR mutations may result in idiopathic (i.e. normocalcaemic) hypercalciuria (IH). We reasoned that such CaSR mutations would lead to an early onset of IH and have sought for them in 12 unrelated children who were normocalcaemic and developed IH nephrol...

Mutations of parafibromin, which is a 531 amino acid protein, are associated with the hyperparathyroidism-jaw tumour (HPT-JT) syndrome. HPT-JT is an autosomal dominant disease that is characterised by the occurrence of parathyroid tumours, which are commonly malignant, and ossifying fibromas of the jaw bones. To date 13 different inactivating germline mutations (3 nonsense, 9 frameshift and one missense altering the initiation codon) of PARAFIBROMIN have been identified in HPT...

SEMDs are a heterogeneous group of skeletal disorders characterised by defective growth and modelling of the spine and long bones. Genetic defects in two inherited SEMDs have been identified and these involve abnormalities of the collagen type II gene located on chromosome 12q12-q13.2, and an ATP sulfurylase/APS kinase gene located on 10q23-34. These are not the cause of the Missouri variant (SEMDMO), which occurs as an autosomal dominant trait in a unique four-gene...