Abstract:
BACKGROUND:Graves' Ophthalmopathy (GO) is a complex eye and orbital disorder that is uniquely linked to Graves' Hyperthyroidism (GH) and has traditionally been considered a cross-reactive immune response against the thyroid stimulating hormone receptor (TSHR) in orbital tissue. However, because there is no direct evidence, such as specific TSHR antibodies or T lymphocytes targeting the orbital tissues in patients with GO compared to those without eye disease, it is important to consider alternative hypotheses for the pathogenesis of GO. The aim of this study was to identify differentially expressed genes within the thyroid of patients with GO and GH as a possible explanation for a thyroid initiated orbital autoimmunity. METHODS:RNA was extracted from thyroid glands of patients with GO (n = 10) and GH (n = 8) post-total thyroidectomy. RNA samples were arrayed on Illumina® Human Ref-8 Expression BeadChips™ representing 20,589 genes. Microarray results of selected genes were validated by quantitative PCR (qPCR) and levels of protein translation measured by Western blot analysis. FINDINGS:Two hundred and ninety-five genes were differentially expressed between patients with GO and GH. Of these, the cardiac calsequestrin gene (CASQ2) was the most highly expressed gene in GO (2.2-fold increase, P < 0.05). The succinate dehydrogenase flavoprotein subunit gene (SDHA) was also significantly up-regulated in GO (P < 0.05), 1.4-fold, while genes encoding the thyroid antigens thyroglobulin, thyroid peroxidase and TSHR were not differentially expressed. qPCR verified up-regulation of CASQ2 and down-regulation BMP7, CD80, IGFBP5, and MYD88 genes in GO. Western blot analysis showed that the average CASQ/GAPDH protein expression ratios for GH and GO were 1.04 and 1.03, respectively. t-Test analysis of data generated a P-value of 0.26, therefore no significant difference was found for CASQ protein expression in thyroid tissue between GH and GO. INTERPRETATION:The skeletal and cardiac calsequestrin proteins share 68.4% amino acid homology. Previous work has shown that RNA levels of skeletal muscle calsequestrin are 4.7 times higher in extraocular muscle (EOM) than in masticatory skeletal muscle (jaw), and cardiac calsequestrin is expressed 2.7 times more in EOM. We postulate that up-regulation of casq2 gene in the thyroid of patients with GH may lead to the production of autoantibodies and sensitized T-lymphocytes, which cross-react with calsequestrin in the EOM of patients who develop ophthalmopathy.
journal_name
Clin Endocrinol (Oxf)journal_title
Clinical endocrinologyauthors
Wescombe L,Lahooti H,Gopinath B,Wall JRdoi
10.1111/j.1365-2265.2009.03753.xsubject
Has Abstractpub_date
2010-10-01 00:00:00pages
522-8issue
4eissn
0300-0664issn
1365-2265pii
CEN3753journal_volume
73pub_type
杂志文章abstract:BACKGROUND:Metadherin (MTDH) protein, also called astrocyte elevated gene-1 (AEG-1) is over expressed in a variety of malignant tumours, and is closely related to tumour invasion and the poor prognosis. OBJECTIVE:This study tries to explore the clinical pathological significance of MTDH expression in a large cohort of...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.12683
更新日期:2015-10-01 00:00:00
abstract::Six girls and one boy with precocious puberty were treated with a superactive LHRH analogue (D-TRP6-LHRH) for periods ranging from 1 year to 2 years and 3 months. In the first phase of the treatment it was administered in combination with cyproterone acetate (CyA) to counteract an early stimulatory effect until inhibi...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1984.tb03433.x
更新日期:1984-04-01 00:00:00
abstract::After administration of intravenous metoclopramide, a dopaminergic receptor blocking agent, no rise in thyroid stimulating hormone (TSH) could be found in patients with chronic renal failure, in contrast to non-uraemic controls. Basal TSH values were normal in the uraemic patients but the TSH response to thyrotrophin-...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1981.tb00687.x
更新日期:1981-11-01 00:00:00
abstract:OBJECTIVE:To compare the outcome of different treatment options used in several cases of non-islet cell tumour hypoglycaemia (NICTH). PATIENTS:Eight cases of NICTH were referred for diagnosis and monitoring following either surgical or medical treatment. METHODS:Serum samples collected throughout the time-course of e...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2004.01989.x
更新日期:2004-04-01 00:00:00
abstract:OBJECTIVE:To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome. DESIGN:An evaluation of the standard clinical practice at one institution. PATIENTS:Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adr...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1991.tb03517.x
更新日期:1991-08-01 00:00:00
abstract:OBJECTIVE:We explored the possibility of a genetic anomaly in the sex determining region of the Y chromosome, SRY gene, known to be equated to the testis determining region. PATIENTS:Four patients with bilateral congenital anorchia, absence of testicular tissue, elevated FSH and a lack of testosterone response to huma...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1993.tb00993.x
更新日期:1993-02-01 00:00:00
abstract:OBJECTIVE:The metabolites of steroidal hormones, including sulphate, glucuronide, and fatty acid (FA) ester derivatives, have received little attention, although these steroid derivatives are essential components in the global assessment of steroid metabolism. The study of FA-derivatives could, in obesity, contribute s...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1999.00669.x
更新日期:1999-02-01 00:00:00
abstract:OBJECTIVE:Little is known about the dose-response relationship of potential, unwanted, effects of inhaled beclomethasone (BDP) on the hypothalamo-pituitary-adrenal (HPA) axis, particularly in nonspecialist clinic settings. The purpose of our study was to investigate the dose-response relationship of inhaled BDP on the ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1997.2391059.x
更新日期:1997-09-01 00:00:00
abstract:OBJECTIVE:Mutations in the GH releasing hormone receptor (GHRH-R) have recently been shown to cause autosomal recessive isolated GH deficiency (IGHD). Patients who are homozygous for GHRH-R mutations have a subnormal GH response to pharmacological agents that stimulate GH secretion and an appropriate response to exogen...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2001.01273.x
更新日期:2001-05-01 00:00:00
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journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.12593
更新日期:2015-01-01 00:00:00
abstract::The case reported is of a 46-year-old woman who had congenital adrenal hyperplasia due to a 21-hydroxylase deficiency, and in whom there was the development of an ACTH secreting pituitary tumour. The patient was untreated with glucocorticoids until the age of 32 years when she presented with infertility. She next pres...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1982.tb01613.x
更新日期:1982-11-01 00:00:00
abstract::Long-term bromocriptine treatment was discontinued in thirty-seven women with hyperprolactinaemic amenorrhoea. After cessation of therapy thirty of the thirty-seven women became hyperprolactinaemic again with amenorrhoea or anovulatory bleeding. Seven of the women continued to have regular ovulatory menstruation but o...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1982.tb03175.x
更新日期:1982-06-01 00:00:00
abstract:OBJECTIVE:Use of the antithyroid drugs (ATDs) thiamazole (MMI) and propylthiouracil (PTU) is associated with a high frequency of side effects. When patients experience side effects with one (the 1st) ATD, it is usually discontinued and another is administered (the 2nd ATD). We investigated side effects associated with ...
journal_title:Clinical endocrinology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2265.2012.04365.x
更新日期:2012-08-01 00:00:00
abstract:CONTEXT:Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIG...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.14367
更新日期:2020-11-11 00:00:00
abstract:OBJECTIVE:To examine the factors influencing the levels of sex hormone-binding globulin (SHBG) in normal postmenopausal women by assessing the relationship between SHBG and measured anthropometric, metabolic and hormonal variables. DESIGN:Cross-sectional, observational study. SUBJECTS AND METHODS:Seventy normal postm...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.2001.01183.x
更新日期:2001-01-01 00:00:00
abstract:OBJECTIVES:Associations between calcium-sensing receptor (CaSR) polymorphisms and serum calcium, PTH and bone mineral density (BMD) have been reported by six studies. However, three other studies have failed to detect such associations. We therefore further investigated three CaSR coding region polymorphisms (Ala986Ser...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2006.02634.x
更新日期:2006-11-01 00:00:00
abstract:UNLABELLED:A diagnosis of bilateral pheochromocytoma warrants exclusion of hereditary pheochromocytoma. OBJECTIVE:To describe the first case of a bilateral pheochromocytoma associated with V804M mutation in the RET proto-oncogene. PATIENTS:The index case was a 54-year-old man with bilateral adrenal masses discovered ...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2007.02830.x
更新日期:2007-07-01 00:00:00
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journal_title:Clinical endocrinology
pub_type: 杂志文章,meta分析
doi:10.1111/cen.13853
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVE:We determined the effects of physiological (non-hypotensive) increments of plasma atrial natriuretic factor (ANF) on the vasopressin and hypothalamic-pituitary-adrenal response to insulin induced hypoglycaemia. DESIGN:Single blind, placebo controlled, randomized study of the effect of vehicle alone or ANF (2...
journal_title:Clinical endocrinology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2265.1993.tb00991.x
更新日期:1993-02-01 00:00:00
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journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.13447
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Macroadenomas represent 50% of pituitary tumours and are often (30%) nonfunctioning. Their immunophenotype suggests differentiation toward a specific pituitary cell line. A substantial proportion of tumours with particularly aggressive behaviour are so called 'silent subtype 3 adenoma'. Its diagnosis require...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2008.03514.x
更新日期:2009-07-01 00:00:00
abstract::In a prospective study of the incidence of thyrotoxicosis sera from 216 thyrotoxic patients in seven English towns were assayed for TSH-receptor antibodies. The incidence of antibody negative thyrotoxicosis correlated closely with the previous prevalence of endemic goitre in the towns (r = 0.9) indicating a high curre...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1985.tb00225.x
更新日期:1985-09-01 00:00:00
abstract::The excretion of FSH, LH, oestrogens and pregnanediol was monitored once weekly in urine samples collected from eight peri-menopausal women aged 44-55 years (median, 52 years). Observations were commenced between 5 and 15 weeks before the menopause and were continued for 22-30 weeks after final menstruation. Amenorrho...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1982.tb01616.x
更新日期:1982-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The rarity of pituitary apoplexy renders it a difficult subject for audit; hence there are no evidence-based standards of optimum care for such patients. The key controversy in management relates to the role of acute neurosurgical intervention. In recent years we have adopted a relatively conse...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2004.02162.x
更新日期:2004-12-01 00:00:00
abstract::The possible relationship between plasma androgenic activity and acne vulgaris was investigated. Plasma testosterone and sex hormone binding globulin (SHBG) levels were determined in healthy girls during different stages of puberty, in healthy adult women and in women with acne vulgaris. Testosterone increase during p...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1982.tb00713.x
更新日期:1982-03-01 00:00:00
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journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/cen.13150
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND/OBJECTIVES:Acylation-stimulating protein (ASP) is an adipose tissue-derived hormone, which stimulates glucose and free fatty acid (FFA) uptake into adipocytes. Changes in ASP metabolism are associated with alterations in lipid metabolism. As postnatal catch-up growth has been associated with dyslipidaemia in...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.2010.03771.x
更新日期:2010-06-01 00:00:00
abstract::Polyglandular syndromes have been described for many years but only one case of panhypopituitarism with adrenal and thyroid insufficiencies has been documented. We present a 69-year-old woman with the initial diagnosis of idiopathic primary hypopituitarism. An associated primary adrenal disease was suspected on low pl...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1111/j.1365-2265.1994.tb03023.x
更新日期:1994-05-01 00:00:00
abstract:OBJECTIVE:Genotype and phenotype heterogeneity in patients with GH insensitivity syndrome suggests that partial defects exist in the GH receptor. Children with partial GH resistance would be expected to have short stature, elevated GH levels and relatively low levels of IGF-I and IGFBP-3. Provocation tests of the GH-IG...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1998.00407.x
更新日期:1998-06-01 00:00:00
abstract:OBJECTIVE:The importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oes...
journal_title:Clinical endocrinology
pub_type: 杂志文章
doi:10.1046/j.1365-2265.1998.00614.x
更新日期:1998-12-01 00:00:00