Endocrine Abstracts

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...

The immune dysregulation, polyendocrinopathy and enteropathy, X-linked syndrome (IPEX), is a rare and devastating condition of male infants. Immune mediated diabetes and enteropathy occur before 6 months of age and other manifestations include hypothyroidism, recurrent infections and eczema. In 2001, IPEX was mapped to Xp11, an orthologous region to that for the murine model of T cell dysregulation, scurfy, and mutations in the forkhead transcription factor gene, FOXP3,...

The thyroid hormones, L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), are essential for skeletal development and regulate bone mineralisation in the adult. T4 is a pro-hormone that is converted to active T3 by the type I and II 5'-iodothyronine deiodinase enzymes (D1 and D2). T4 and T3 are substrates for the type III 5-deiodinase enzyme (D3) which catalyses the irreversible production of inactive metabolites. The deiodinases are expressed widely in T3-target tissues and the...

Does Iodide Modulate The Biological Outcome of Activating Thyrotropin Receptor Mutations?Dr. F. Al-Khafaji and Dr. M. LudgateHyperthyroidism is caused by pathogenic activation of the thyrotropin receptor (TSHR) either by the thyroid stimulating antibodies of Graves' disease (GD) or activating TSHR mutations. These produce nodular goitre or familial hyperthyroidism. The pathogenic mechanism predominating varies according to the iodide intake, with nodular goitre account...

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 individuals. Rapid detection and treatment by neonatal screening and administration of T4, is essential to prevent severe mental retardation and impaired growth.We report on two Welsh siblings, detected by neonatal screening, which had normal sized and placed glands but negative isotope uptake. Mutations resulting in CH are known to occur in 11 known genes, given the clinical presentation, we investigated the...

Background:In thyroid autoimmune conditions such as Graves' disease, thyroid cells die by apoptosis (programmed cell death).Dysregulation of pro- and anti-apoptotic genes may be critical to the induction of the destructive process via the activation of a sequence of caspases (proteases). Conventionally, apoptosis occurs via 2 main pathways: the Intrinsic pathway mediated by mitochondria and the Extrinsic pathway mediated by the activation of death receptors (Fas and TN...

When cultured in serum-free conditions, primary cultures of human thyroid cells display TSH-dependent iodide uptake and organification and iodide-dependent thyroid hormone synthesis. High iodide concentrations (>1 microM) inhibit thyroid hormone synthesis but iodide (0.1 microM) is obligatory for thyroid hormone secretion into the medium. We have performed in vitro studies examining the regulation of iodide transport and organification in cells preincubated in varying conce...

Background : The aim of this study was to investigate trends in incidence, mortality and survival for thyroid cancer, in Scotland.Methods : Thyroid cancer registration data (for the period 1960-1997) were obtained from the Scottish Cancer Registry and death registration data (1960-1999) were provided by the General Register Office, Scotland. Trends were examined using rate calculations and relative survival analysis.Results : During the period 1960-1997, the age-standa...

Normal pregnancy is associated with significant but reversible changes in thyroid function. However, maternal thyroid dysfunction during early pregnancy has been associated with neuro-intellectual impairment of the child. The CATS study, a randomised controlled study, has been initiated in order to ascertain if screening for abnormalities in thyroid function in early pregnancy (8 - 16 weeks gestation), with thyroxine replacement in appropriate cases, would be effective in redu...

Background: Abnormalities of cardiac autonomic function may contribute to excess vascular mortality reported in treated hyperthyroidism.Aim: To evaluate cardiac autonomic function in hyperthyroidism before and after effective anti-thyroid therapy.Methods: 405 consecutive unselected patients with hyperthyroidism were recruited with 405 age- and sex-matched euthyroid controls for matched comparisons; all had 24-hour Holter monitoring. Patients were reassessed when render...

The autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis (HT), are thought to be caused by complex interactions between genetic and environmental factors, which result in an organ-specific autoimmune response being directed against the thyroid gland. GD and HT, although clinically distinct, share many immunological and histological features. Several potential susceptibility genes for AITD have been investigated, although to date only the HLA an...

Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the initiation and regulation of the cytokine cascade during an inflammatory response and is, therefore, a good candidate for involvement in the development of autoimmune disease. The TNF-alpha gene has been mapped to chromosome 6p21.3 and many single nucleotide polymorphisms (SNPs) have been detected within the gene that could affect its function. The allele frequencies of these SNPs and their relationship to...

Objective: Many patients receiving thyroid hormone replacement therapy complain of persistent lethargy and related symptoms even with normal TSH levels. However, it remains unclear whether this is related to thyroxine replacement or coincidental psychological morbidity.Design: Using general practice computer records, 961 patients on thyroxine (minimum of 4 months) and their age- and sex-matched controls were identified and sent a two-page questionnaire, comprising the shor...

Objective: To investigate a possible association of DRB1, DQA1 and DQB1 alleles with the chronic autoimmune thyroiditis (AT) development in patients with diabetes mellitus type 1 (DM1) manifested between 18 to 40 years of age. Patients and methods: In 118 patients with DM1 (age at DM1 diagnosis 28.0 (6.9) years, duration of DM1 14.0 (6.3) years) HLA-DRB1, -DQA1 and -DQB1 alleles were analysed by sequence specific oligonucleotide probes and sequence specific primers. AT was pre...

The high prevalence of thyroid disease necessitates efficient and effective monitoring. We expanded a hospital-based register to a managed clinical network for almost 10,000 patients with thyroid disease. Evaluation of our network compared to register data from 1991 demonstrates changing trends in treatment of hyperthyroidism. Use of radio-iodine significantly increased (58 percent v 44 percent; p less than 0.001) with a reduction in thyroid surgery (34 percent v 47 percent; p...

Introduction: Somatostatins are physiological down regulatory proteins that act via 5 different transmembrane receptors (SSTR1-5, including isoforms SSTR-2a & 2b) via GTP binding proteins. The aim of this study was to determine the distribution of somatostatin receptors in thyrocytes of different thyroid pathologies.Method: Formalin fixed paraffin embedded sections from archival tissue were immunostained. Sections underwent dewaxing and rehydration before microwave ant...

Patient information is increasingly well provided, but little is known of patients' actual understanding of their conditions. The aim of this study was to determine the level of knowledge about thyrotoxicosis and its treatment among patients attending the endocrine clinic. Consecutive patients who had received antithyroid drugs were identified from the clinic database and asked to respond to a postal questionnaire. Ethical approval was obtained for the study.Questionnaires...

The relationship between serum TSH and thyroid autoantibodies is frequently used to classify thyroid disease both overt and subclinical. Further debate has centred on the validity of the cutoff point for serum TSH elevation (generally between 4-5 mU/l) which it has been suggested is inappropriately high. The significance of the presence of thyroid autoantibodies (hereafter termed antibody positivity) in extrathyroidal disease is unclear but an increased prevalence has been rep...

Objective : To determine whether simultaneous ultrasonography at the time of scintigraphy affects the diagnosis or diagnostic confidence in patients with hyperthyroidism.Method Used: A retrospective study was carried out involving 100 patients who attended for investigation of hyperthyroidism between 01/07/01 and 31/03/02. All patients ( 15 male, 85 female) had simultaneous radioisotope scanning and ultrasound of their thyroid glands performed and reported. Subsequently th...

Radioactive iodine scanning and ablative radioactive therapy (RAI) are mainstays of follow-up and therapy in patients with differentiated thyroid carcinoma. TSH levels of 30 or greater are recommended as the levels required for effective use of RAI (see recent British Thyroid Association guidelines).To clarify our own practice we have studied 20 consecutive patients undergoing ablative RAI for thyroid carcinoma (10 papillary, 8 follicular and 2 mixed). The fourteen who had...

BackgroundPropylthiouracil treatment of Graves' disease has been postulated to provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, particularly myeloperoxidase (MPO)-ANCA, however it is unclear whether the abnormal immune environment of autoimmine thyroid disease influences the development of ANCA.MethodsThe occurrence of ANCA and the relationship to thionamide treatment was investigated in 407 patients' with Graves' disease, 200 with Hashimo...

The functional interleukin-4 receptor is a heterodimeric complex composed of the IL-4 receptor alpha chain and the common cytokine gamma chain. The interleukin-4 receptor (IL-4R) gene is located on human chromosome 16p12.1-11.2. A polymorphism at codon 50 of the alpha chain alters the receptor response to the Th2 cytokine interleukin-4 (IL-4). The allele with the amino acid isoleucine at position 50 (Ile50) upregulates receptor activity in response to binding with IL-4 ...

Background: It has been proposed that in the acute, untreated phase of thyrotoxicosis analysis of the peripheral eosinophil to monocyte ratio is a useful parameter to help differentiate thyroiditis from other forms of thyrotoxicosis without the need for radioiodine uptake scanning. (1).Methodology: We performed a retrospective search of our thyroid database for patients who had had a full blood count and radioiodine uptake scan prior to the commencement of antithyroid medi...

High dose intravenous methylprednisolone therapy is used in patients with severe thyroid-associated ophthalmopathy (TAO) and other inflammatory disorders. Although in the short-term it appears to be safe, the acute metabolic effects of this regimen have not been studied in detail.We studied 15 patients with severe TAO, aged 59 ± 10 (mean ± SD) years. One patient was known to have type 2 diabetes. Each patient received 500 mg of iv methyprednisolone daily on t...

Hyperthyroidism is diagnosed in pregnancy in about 0.1 - 0.4% of patients. Graves' disease is the commonest cause of thyrotoxicosis in pregnant women. The natural course of Graves' disease in pregnancy is characterised by an exacerbation of symptoms in the first trimester and during the post partum period. Symptoms usually tend to improve in the second half of pregnancy.We describe a patient who was diagnosed with Graves' disease in the third trimester of pregnancy. A 32 y...

(i)Background (i): Treatment of Graves' disease involves a choice of several methods such as medical treatment, radioactive iodine and surgery. However, primary treatment of this condition remains controversial and shows considerable geographical variations worldwide.(i)Objective (i): In this study we examined the rate of complete remission (without relapse), relapse and complications of the different treatment modalities (carbimazole, radioactive iodine and subtotal thyro...

Background: Hyperhomocysteinemia is an independent risk factor foratherosclerosis (1,2). Elevated plasma total homocysteine(t-Hcy) levels havebeen described in primary hypothyroidism (3,4). Subclinical hypothyroidismhas also been found to be associated with atherosclerosis (5).Hypothyroidism decreases hepatic levels of enzymes involved in theremethylation pathway of homocysteine and renal excretion of t-Hcy (6,7).The present study evaluates t-Hcy in sub...