Thyroid Conditions : clipclip

Autoantibodies highly increased in patients with t...[Cell Mol Immunol. 2007] - PubMed Result

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clipped by chiroted Jul 09, 2007

antibodies antithyroid Graves's Hashimoto's

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Cell Mol Immunol. 2007 Jun;4(3):233-6.

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Autoantibodies highly increased in patients with thyroid dysfunction.

Wen WB , Liu FY .

First People's Hospital of Yuci District, Jinzhong, Shanxi, China.

To evaluate the significance of antithyroid antibodie levels, five hundred and twenty-six patients with thyroid diseases and 292 health subjects from Yuci District, Shanxi Province, China, were studied. Serum levels were determined for thyroid hormone receptor antibody (TRAb), microsomal antibody (TMAb) and thyroglobulin antibody (TGAb). Among patients, the percentages for nodular goiter and thyroid adenoma, Graves' disease, and Hashimoto's thyroiditis are 44.1%, 19.6% and 17.7%, respectively. The ratios of female to male were 2.0 to 15.6. Antibody-positive patients for TMAb, TGAb and TRAb were detectable as 94.6%, 76.3% and 20.4% for Hashimoto's thyroiditis, and 40.0%, 30.0% and 90.3% for Graves's disease. In conclusion, the high levels of the TRAb in Graves' disease, and those of the TGAb/TMAb in Hashimoto's thyroiditis and idiopathic hypothyroidism are meaningful for characterizing the epidemiological basis of the diseases and for using as prognostic indicators for the relapse in individual patients.

[Significance of combining tests of thyroid autoan...[Zhonghua Yi Xue Za Zhi. 2003] - PubMed Result

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clipped by chiroted Jul 09, 2007

autoantibodies Graves's Hashimoto's hyperthyroid hypothryoid

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Zhonghua Yi Xue Za Zhi. 2003 Jun 10;83(11):940-2. Links

[Significance of combining tests of thyroid autoantibodies in differential diagnosis between Graves's disease and Hashimoto's hyperthyroidism]

[Article in Chinese]

Hu YM , Liu W , Lu GH .

Department of Internal Medicine, Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China.

OBJECTIVE: To investigate the differential diagnosis between Graves's disease and Hashimoto's hyperthyroidism to improve positive diagnostic rate in Hashimoto's hyperthyroidism, to facilitate proper management. METHODS: Cytological examination was conducted by fine needle biopsy (FNB) on the thyroids of patients with hyperthyroidism diagnosed by clinical data, including 22 cases of Hashimoto's hyperthyroidism, 5 males and 17 females, aged 39 +/- 12, and 49 cases of Graves's disease, 20 males and 29 females, aged 41 +/- 11. Thyroid auto-antibodies-thyroid peroxidase antibody (TPOAb), thyroid microsomal antibody (TMA), thyroglobulin antibody (TGA), thyroid-stimulating hormone receptor antibody (TRAb), and free serum triiodothyronine (FT3), free thyroxin (FT4), and serum thyroid-stimulating hormone (S-TSH) were tested. The correlation between the pathology of thyroid and different autoantibodies and thyroid hormone was analyzed. RESULTS: TRAb was 42.28 +/- 75.89 in Graves disease group, significantly higher than that in Hashimoto's hyperthyroidism group (5.77 +/- 12.69, P < 0.001). FT3 was 16.13 +/- 9.95, significantly higher than that in Hashimoto's hyperthyroidism group (9.54 +/- 6.76, P < 0.01). In Graves's disease group the positive rates for TRAb, TPOAb, TMA, and TGA were 83.67%, 75.51%, 57.14% and 48.98% respectively. In Hashimoto's hyperthyroidism group, the positive rate for TRAb was 13.64%, and the positive rates for the rest autoantibodies were all 86.36%. The double positive rate of TPOAb and TGA was 86.36% in Hashimoto's hyperthyroidism group, significantly higher than that in Graves's disease group (48.98%). There was a positive association between TRAb and FT3, and between diffuse and symmetric increased size of thyroid and FT3 TRAb. CONCLUSION: Comprehensive analysis of TRAb, TPOAb, TGA, and FT3 is helpful to the differential diagnosis between Graves's disease and Hashimoto's hyperthyroidism.

[The relationship between serum thyroid autoantibo...[Zhonghua Nei Ke Za Zhi. 2006] - PubMed Result

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clipped by chiroted Jul 09, 2007

autoantibodies graves Hashimoto's hyperthyroid hypothyroid Thyroid

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Zhonghua Nei Ke Za Zhi. 2006 Feb;45(2):95-9. Links

[The relationship between serum thyroid autoantibodies, iodine intake, development and prognosis of Graves' disease]

[Article in Chinese]

Chen W , Man N , Li YS , Shan ZY , Teng WP .

Endocrinology Department, Endocrinology Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.

OBJECTIVE: To investigate the relationship of thyroid autoantibodies including serum thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody (TSBAb) and iodine intake with the development and prognosis of Graves' hyperthyroidism. METHODS: A total of 63 subjects with overt hyperthyroidism were screened out from 3 Chinese rural communities with different iodine intakes at first survey. Serum TSAb, TSBAb, thyrotropin binding inhibitory immunoglobulin (TBII), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) were detected. The patients were followed up 2 years later. TSAb and TSBAb were measured with recombinant human thyrotropin receptor (rhTSHR)-Chinese hamster ovary cell (rhTSHR-CHO cell) bioassay. RESULTS: At the first survey, the prevalences of positive TSAb, TBII and TSBAb were found in 80.9%, 61.7% and 6.4% of the patients with Graves' disease respectively. TSAb and/or TBII were positive in 91.5% of the patients. The consistent rate of TSAb and TBII was 59.6% in the cases. All indexes mentioned above were higher in the patients than in healthy controls. Positive correlations were found between TSAb and TBII (r = 0.407), TSAb and thyroglobulin (r = 0.301), TSAb and thyroid volume (r = 0.317) respectively. The prevalence of positive TSAb (91.7%) in Graves' patients in iodine excessive area are significantly higher than those in iodine mildly deficient area (66.7%). The positive rates and the titers of TBII, TPOAb and TGAb were not different statistically among the patients in the three communities. At follow-up, the patients with Graves' hyperthyroidism were classified into euthyroid group (G1) and hyperthyroid group (G2) according to their outcomes of the disease. The TSAb titers and the thyroid volume in the cases of G1 decreased significantly, whereas the patients with highly positive TPOAb titers in the first survey and the follow-up were hard to become euthyroid and TSAb may be the secondary factor influencing the thyroid as compared with TPOAb. CONCLUSION: TSAb is more significant than TBII in diagnosing and predicting the outcomes of Graves' hyperthyroidism. The application of both TSAb and TBII could raise the positive rates of thyrotrophin receptor antibody tests. TSAb, TPOAb titers and thyroid volume were factors influencing the prognosis of Graves' hyperthyroidism.

Congenital hypothyroidism with goitre caused by ne...[Clin Endocrinol (Oxf). 2007] - PubMed Result

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clipped by chiroted Jul 03, 2007

goiter hypothyroid

Notes by chiroted: DNA: all known and unknown inactivating TG mutations of the thyroglobulin gene, plus iodine. Do w/DNA damage repair gene's and proteins to correct the nucleotide insertion mutation in the TG gene

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Clin Endocrinol (Oxf). 2007 May 28; [Epub ahead of print] Links

Congenital hypothyroidism with goitre caused by new mutations in the thyroglobulin gene.

Caputo M , Rivolta CM , Esperante SA , Gruñeiro-Papendieck L , Chiesa A , Pellizas CG , González-Sarmiento R , Targovnik HM .

Laboratorio de Biología Molecular, Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Context Thyroid dyshormonogenesis is associated with mutations in the thyroglobulin (TG) gene and characterized by normal organification of iodide and low serum TG. These mutations give rise to congenital goitrous hypothyroidism, transmitted in an autosomal recessive mode. Objectives The aim of this study was to identify new mutations in the TG gene in an attempt to increase the understanding of the molecular basis of this disorder. Three unrelated patients with marked impairment of TG synthesis were studied. Methods The promoter and the complete coding regions of the TG gene, along with the flanking intronic regions, were analysed by direct DNA sequencing. Results Four different inactivating TG mutations, three novel mutations (c.548G>A, p.C164Y; c.759-760insA, p.L234fsX237; c.6701C>A, p.A2215D) and one previously identified mutation (c.886C>T, p.R277X) were identified. Multiple sequence alignment study revealed that the wild-type cysteine residue at position 164 is strictly conserved in the TG of all the species analysed, whereas the wild-type alanine residue at position 2215 is well conserved in the TG and acetylcholinesterase (AChE) of all the species analysed except in rabbit AChE, in which it is substituted by glutamic acid. Conclusions We report three patients with congenital hypothyroidism with goitre caused by two compound heterozygous mutations, p.C164Y/p.L234fsX237 and p.R277X/p.A2215D, and one homozygous mutation, p.R277X, in the TG gene. To our knowledge this is the first report of the presence of a nucleotide insertion mutation in the TG gene.

Candida & Thyroid Disease

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clipped by chiroted May 30, 2007

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Am J Hum Genet. 2001 Oct;69(4):791-803. Epub 2001 Aug 21.

Celiac Disease, Thyroidectomy, Gluten-free diet

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clipped by chiroted Mar 22, 2007

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Ann Endocrinol (Paris). 2006 Sep;67(4):357-9.

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[Celiac disease revealed by hypocalcemia complicating total thyroidectomy: a case report]

[Article in French]

Service Endocrinologie-Diabetologie, Hopital La Rabta, 1007 Tunis, Tunisia.

In order to illustrate a particular circumstance of diagnosis of celiac disease, we report the case of 54-year-old women with a history of thyroid enlargement with normal thyroid function and positive anti-peroxidase antibodies. Immediately after total thyroidectomy with preservation of the parathyroid glands, she developed tetany with total serum calcium level at 50mg/l. Intravenous calcium infusion increased the calcium level and led to resolution of hypocalcemia-induced signs but there was no result when calcium and vitamin D were taken orally. The diagnosis of malabsorption was very probable in light of the family history of celiac disease, the anemia and the hypoalbuminemia. The diagnosis was confirmed by antibodies assay and endoscopy. The PTH level was less than 1 pg/l and radiography showed signs of hyperparathyroidism. Gluten-free diet, calcium and vitamin D led to an improvement of serum calcium.

Thyroid disorders In pts with Celiac Disease

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clipped by chiroted Mar 22, 2007

Celiac disease Gluten Thyroid

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J Clin Gastroenterol. 2006 Jan;40(1):33-6.

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Thyroid disorders in Brazilian patients with celiac disease.

Gastroenterology Service, Cajuru Hospital, Pontifical Catholic University of Parana, Brazil. loretekotze@hotmail.com

INTRODUCTION/AIM: Patients with celiac disease (CD) can develop a gluten related autoimmune disorder that affects not only the small intestine but other tissues as well. An increased prevalence of autoimmune diseases has been reported, particularly autoimmune thyroiditis. The aim of this study was to characterize thyroid disorders in patients with CD. PATIENTS/METHODS: Fifty-two patients with CD (43 female, 9 male; mean age, 41.1 years) were studied. Nine were on a gluten-free diet (GFD). They were divided into four groups: Group 1, without thyroid involvement (n=30); Groups 2A-C, with thyroid involvement (n=22); Group 2A, subclinical hypothyroidism (n=11); Group 2B, clinical hypothyroidism (n=10); and Group 2C, other thyroid disorders (n=1). CD was confirmed by serologic and histologic criteria. Thyroid involvement was detected by measurement of thyroid stimulating hormone (TSH) and anti-thyroperoxidase antibodies (anti-TPO). RESULTS: Increased levels of TSH and/or anti-TPO levels were detected in Groups 2A (21.1%) and 2B (19.2%). The patients of Group 2B presented clinical symptoms of hypothyroidism before the diagnosis of CD, and 5 of these patients were receiving levothyroxine. One woman (Group 2C; 1.92%) had a medullary carcinoma. There was statistical significance between the age when thyroid disease was diagnosed (current age) and the age of CD diagnosis between Groups 1 and 2B. Patients with thyroid involvement presented associated diseases such as diabetes mellitus (2), Down's syndrome (2), ulcerative colitis (1), and dermatitis herpetiformis (2). CONCLUSIONS: Our findings demonstrated an increased prevalence of thyroid disorders (hypothyroidism, 19.2%; and subclinical hypothyroidism, 21.2%), and other associated diseases in celiac patients, even on a GFD, increasing with the age of the patients. Screening for associated diseases is recommended for patients with CD, independent of age at diagnosis or treatment duration.

Graves Regulating Role of endocrine and Immune Systems

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clipped by chiroted Jan 26, 2007

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Exp Clin Endocrinol Diabetes. 1996;104(2):172-6. Links

Parameters of respiratory burst and arachidonic acid metabolism in polymorphonuclear granulocytes from patients with various thyroid diseases.

First Department of Medicine, University Medical School, Debrecen, Hungary.

The oxidative processes (oxygen consumption, superoxoid anion generation, arachidonic acid cascade) of human polymorphonuclear granulocytes (PMNs) obtained from patients suffering from thyroid disorders of autoimmune origin (Graves' disease and Hashimoto's thyroiditis), and non autoimmune origin (toxic adenoma) were investigated. All Graves' and toxic adenoma patients were hyperthyroid. Hashimoto's thyroiditis patients were euthyroid. Healthy age and sex matched volunteers served as controls. The results are as follows: 1) In PMNs from both hyperthyroid groups (Graves' disease and toxic adenoma), independently from the autoimmune origin of the disease, a significantly increased Antimycin A sensitive mitochondrial oxygen consumption and a slightly increased superoxide anion generation were detected. 2) In both autoimmune thyroid disease groups (Graves' disease and Hashimoto's thyroiditis)--depending on the functional state of the thyroid gland--a significantly altered intracellular killing activity was measured. 3) An increased arachidonic acid cascade--triggered by opsonized zymozan (OZ)--was detected in both autoimmune thyroid diseases. The increased arachidonic acid cascade was sensitive to phospholipase A2 inhibiting Mepacrin treatment. 4) The PMNs from both autoimmune thyroid diseases produced large amount of leukotriens (LTs)--LTC4 and LTB4--after stimulation through their Fc receptors but the synthesis of prostagalandins (PGs) has not changed. There are no data indicating local, specific effects of circulating leukotriens in the thyroid gland itself, but based on authors' data, their general, regulating role on both the endocrine-- as well as on the immune system--seems to be plausible.

Graves Disease Protein and Yeast Mitochondrial carrier Leu5p

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clipped by chiroted Jan 26, 2007

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Mol Cell Biol. 2001 Feb;21(4):1089-97.

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The yeast mitochondrial carrier Leu5p and its human homologue Graves' disease protein are required for accumulation of coenzyme A in the matrix.

Institut fur Zytobiologie und Zytopathologie der Philipps-Universitat Marburg, 35033 Marburg, Germany.

The transport of metabolites, coenzymes, and ions across the mitochondrial inner membrane is still poorly understood. In most cases, membrane transport is facilitated by the so-called mitochondrial carrier proteins. The yeast Saccharomyces cerevisiae contains 35 members of the carrier family, but a function has been identified for only 13 proteins. Here, we investigated the yeast carrier Leu5p (encoded by the gene YHR002w) and its close human homologue Graves' disease protein. Leu5p is inserted into the mitochondrial inner membrane along the specialized import pathway used by carrier proteins. Deletion of LEU5 (strain Deltaleu5) was accompanied by a 15-fold reduction of mitochondrial coenzyme A (CoA) levels but did not affect the cytosolic CoA content. As a consequence, the activities of several mitochondrial CoA-dependent enzymes were strongly decreased in Deltaleu5 cells. Our in vitro and in vivo analyses assign a function to Leu5p in the accumulation of CoA in mitochondria, presumably by serving as a transporter of CoA or a precursor thereof. Expression of the Graves' disease protein in Deltaleu5 cells can replace the function of Leu5p, demonstrating that the human protein represents the orthologue of yeast Leu5p. The function of the human protein might not be directly linked to the disease, as antisera derived from patients with active Graves' disease do not recognize the protein after expression in yeast, suggesting that it does not represent a major autoantigen. The two carrier proteins characterized herein are the first components for which a role in the subcellular distribution of CoA has been identified.

Grave's Etiology

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clipped by chiroted Jan 26, 2007

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Thyroid. 2003 Mar;13(3):233-8.

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A major role for non-major histocompatibility complex genes but not for microorganisms in a novel murine model of Graves' hyperthyroidism.

Department of Pharmacology 1, Nagasaki University School of Medicine, Nagasaki, Japan. nagayama@net.nagaski-u.ac.jp

The etiology of Graves' disease is multifactorial. We investigated the role of genetic and environmental factors on the susceptibility to Graves' hyperthyroidism using a new murine model. Intramuscular injection of recombinant adenovirus expressing the thyrotropin receptor (AdCMVTSHR) induces Graves'-like hyperthyroidism (thyrotropin receptor [TSHR] antibodies, elevated thyroxine, and diffuse goiter) in more than 50% of female BALB/c mice. The relative contributions of major histocompatibility complex (MHC) and non-MHC genes on the susceptibility to hyperthyroidism were studied by immunizing BALB/c (H-2d), BALB.K (H-2k), and DBA/2J (H-2d) mice with AdCMVTSHR. Hyperthyroidism developed in approximately 50% of BALB/c and BALB.K mice but only 5% of DBA/2J mice, indicating a major role for non-MHC genes in disease development. The effect of environmental microorganisms was evaluated by comparing disease incidence in BALB/c mice maintained in pathogen-free conditions versus those in nonsterile, conventional housing, as well as by coadministering microorganism components (Escherichia coli lipopolysaccharide or yeast zymosan A) as adjuvants with AdCMVTSHR. Neither type of exposure to environmental pathogens influenced disease induction. In conclusion, non-MHC genes, but not infectious organisms, play a major role in the etiology of this novel murine model of Graves' disease.

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