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PubMed2003

The presence of the antigliadin antibodies in autoimmune thyroid diseases.

AIMS: To investigate the presence of the antigliadin antibodies in the patients with Graves' disease and Hashimoto's thyroiditis. METHODOLOGY: Four hundred patients with autoimmune thyroid disease (280 Graves' disease and 120 Hashimoto's thyroiditis ) were included in the study. The patients with celiac sprue patients were excluded. For the diagnosis of autoimmune thyroiditis, blood levels of thyrotropin (TSH), free thyroxine (FT4), and the titration of thyroid autoantibodies (TgAb and TmAb) were measured, and the thyroid gland was ultrasonographycally evaluated. After the diagnosis of autoimmune thyroid disease was established, the titration of antigliadin antibodies (Ig A and B) were routinely detected. RESULTS: Twenty two patients (5.5 per cent) with autoimmune thyroiditis had positive antigliadin antibodies. Polyglandular endocrine syndrome was diagnosed in most of these patients. CONCLUSIONS: We claim that polyglandular endocrine syndrome is the commonest cause of positivity of antigliadin antibodies in the patients with autoimmune thyroid disease.

Antibodies↗
PubMed2003

Surgery versus pharmacotherapy of benign thyroid diseases.

Surgical management of benign thyroid diseases (BTDs) has been a topic of interest and confusion for many years. Almost 80% of thyroidectomies at an average endocrine surgical unit are carried out for BTDs. Resistance to surgical intervention in BTDs has been based on the belief that increased complication rate is inherent in its use, this is despite the potential advantages in terms of confirming the benign nature of the lesion, controlling the disease, and relieving local symptoms of large neck mass. Benign thyroid diseases are more likely to occur in middle-aged women living in iodine deficient areas, or have a family history of goiter, or in patients taking iodine-containing drugs, like amoidarone, or in patients with previous history of x-ray exposure. However, the physician must be careful in making the diagnosis of BTDs in patients at the extremes of age or in the presence of positive history of radiation, or in patients with family history of thyroid or colon cancer. In this article we will review the etiology, epidemiology, diagnostic methodologies and the recent trends in the surgical and medical management of BTDs.

Goiter, Nodular↗
PubMed2005

[Detection of cytokeratin 19 and thyroperoxidase expressions in the diagnosis of thyroid diseases].

OBJECTIVE: To investigate the value of detecting cytokeratin 19(CK19) and thyroperoxidase (TPO) expression in the diagnosis of thyroid diseases including thyroid carcinoma, multinodular goiter, adenoma and Hashimoto thyroiditis. METHODS: SP immunohistochemistry was used to detect the expressions of CK19 and TPO in paraffin-embedded thyroid tissue specimens obtained from 62 patients with thyroid carcinoma (30 with papillary carcinomas, 22 with follicular variant of papillary carcinomas, and 10 with follicular carcinomas) and 44 with benign thyroid diseases (including 22 with multinodular goiters, 14 with adenoma, and 8 with Hashimoto thyroiditis). RESULTS: CK19 expression was detected in 96.8% of the thyroid carcinomas and in 4.5% of benign thyroid diseases, demonstrating a significant difference in CK19 expression between the two thyroid diseases (P<0.01). TPO expression was found in 100% of benign thyroid disease and in 3.2% of thyroid carcinoma, showing also a significant difference between them (P<0.01). CONCLUSION: CK19 and TPO can be important molecular markers for diagnosing thyroid carcinoma.

Adenoma↗
PubMed2003

Expression of human pendrin in diseased thyroids.

We examined pendrin expression in various diseased thyroid tissues by immunohistochemistry (IHC) using antiserum raised against human pendrin and by real-time quantitative RT-PCR. In normal thyroids the antiserum reacted with the apical membrane of follicular cells and its immunoreactivity was faint. In Graves' thyroids, the IHC expression of pendrin appeared in a pattern similar to that of normal thyroids but it was more extensive and stronger, especially in areas showing marked proliferation of follicular cells. The immunoreactivities of pendrin in nodular goiters varied from case to case. In follicular adenomas, pendrin was localized in the follicle-forming parts of the tumor but was negative in trabecular parts. Pendrin was negative in all follicular carcinomas, papillary carcinomas, and in one case of medullary carcinoma. In quantitive mRNA analysis, the relative values of pendrin mRNA were significantly low in papillary carcinoma (p<0.01), whereas the values in other diseased thyroids were not significantly different from those in normal thyroids. These results suggest that pendrin may play a role in thyroid hormone production as the apical porter of chloride/iodide and investigation of pendrin leads to a better understanding of functional aspects of the iodine transportation system in thyroid diseases.

Carrier Proteins↗
PubMed1996

IDDM and autoimmune thyroid disease in the pediatric age group.

Diabetic patients have increased chances of developing autoimmune thyroid disease. Thyroid autoantibodies (Th-AAb) are more frequent in IDDM children than in the general population, ranging between 7 and 40%. As markers of thyroid autoimmunity, we assessed Th-AAb (MsA and TgA) cross-sectionally in 212 children and adolescents (93 girls and 119 boys) aged 1.2-21 years with IDDM from 0-18 years, and longitudinally in 90/212 (43 girls and 47 boys) at diagnosis and during a 3-10 year follow-up. In the cross-sectional study Th-AAb were found in 22/93 girls (23.7%) and 13/119 boys (10.9%). In the longitudinal study Th-AAb were observed at diagnosis in 6 patients, and during the follow-up in 9 girls. In 11/15 Th-AAb positive patients anti-nuclear antibodies were also present. Hormonal assessment revealed hypothyroidism in 3 girls (afterwards on replacement therapy), thyroid ultrasonography showed abnormal patterns in 5 girls, fine needle aspiration biopsy confirmed Hashimoto's thyroiditis in 9 (8 girls and 1 boy), with a higher frequency than that reported among healthy subjects (1-2%). Thyrotoxicosis also occurs with increased frequency in diabetic children than in the general population. We observed Graves' disease in only 1/212 IDDM patients, a 13 year-old boy in whom thyrotoxicosis developed 4 years after diabetes was diagnosed. The high prevalence of thyroid autoimmunity in our patients, particularly in females, suggests that diabetic children and adolescents should be screened for thyroid autoimmunity even if asymptomatic for hypo- or hyperthyroidism. Patients with IDDM and autoimmune thyroid disease should be evaluated for autoantibodies against other organs, such as adrenal glands and gastric mucosa. It is known that patients affected by type 1 (insulin-dependent) diabetes mellitus (IDDM) may have autoantibodies against different organs, such as thyroid, adrenal glands, gastric mucosa, parathyroid, with or without evident dysfunction of the target organ /1-8/. Among organ-specific disorders, autoimmune thyroid disease (ATD) is frequently associated with IDDM and the presence of thyroid autoantibodies (Th-AAb) has been considered a risk factor for the development of hypo- or hyperthyroidism /9/.

Adolescent↗
PubMed2002

ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 37, August 2002. (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy.

Because thyroid disease is the second most common endocrine disease affecting women of reproductive age, obstetricians often care for patients who have been previously diagnosed with alterations in thyroid gland function. In addition, both hyperthyroidism and hypothyroidism may initially manifest during pregnancy. Obstetric conditions, such as gestational trophoblastic disease or hyperemesis gravidarum, may themselves affect thyroid gland function. This document will review the thyroid-related pathophysiologic changes created by pregnancy and the maternal-fetal impact of thyroid disease.

Female↗
PubMed2024

Epigenome-wide Association Study Shows Differential DNA Methylation of MDC1, KLF9, and CUTA in Autoimmune Thyroid Disease.

CONTEXT: Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto disease (HD), which often run in the same family. AITD etiology is incompletely understood: Genetic factors may account for up to 75% of phenotypic variance, whereas epigenetic effects (including DNA methylation [DNAm]) may contribute to the remaining variance (eg, why some individuals develop GD and others HD). OBJECTIVE: This work aimed to identify differentially methylated positions (DMPs) and differentially methylated regions (DMRs) comparing GD to HD. METHODS: Whole-blood DNAm was measured across the genome using the Infinium MethylationEPIC array in 32 Australian patients with GD and 30 with HD (discovery cohort) and 32 Danish patients with GD and 32 with HD (replication cohort). Linear mixed models were used to test for differences in quantile-normalized &#x3b2; values of DNAm between GD and HD and data were later meta-analyzed. Comb-p software was used to identify DMRs. RESULTS: We identified epigenome-wide significant differences (P < 9E-8) and replicated (P < .05) 2 DMPs between GD and HD (cg06315208 within MDC1 and cg00049440 within KLF9). We identified and replicated a DMR within CUTA (5 CpGs at 6p21.32). We also identified 64 DMPs and 137 DMRs in the meta-analysis. CONCLUSION: Our study reveals differences in DNAm between GD and HD, which may help explain why some people develop GD and others HD and provide a link to environmental risk factors. Additional research is needed to advance understanding of the role of DNAm in AITD and investigate its prognostic and therapeutic potential.

Humans↗
PubMed1996

[Morphology and clinical features of autoimmune thyroid diseases].

The aetiopathogenesis of autoimmune thyroid diseases is the subject of various partly contradicting hypotheses and theories. Morphologically, these illnesses are associated with a broad spectrum of overlapping changes. Thus, pathology either can not serve as the logical basis for a new classification of autoimmune thyroid diseases. This overview therefore makes use of the conventional nomenclature of clinically established entities and includes recently defined lesions. Besides histological characteristics details of differential diagnostic value are presented in the context of clinical and laboratory data relevant for pathological typing.

Autoantibodies↗
PubMed1989

[Standardization of diagnostic studies in thyroid diseases].

Standardized diagnosis of thyroid diseases includes 3 levels of diagnostic investigation proper based on the syndromic approach and distributed by 3 levels of providing medical care to population. At the 1st level of primary health care the use of "active" detectability ensures timely detection of symptomless thyroid cancer at early stages and early detection of the syndrome of its disturbance and makes it possible to start the prevention of functional and organic changes. At the second level of providing specialized medical care the role of adjuvant diagnostic methods acquires more importance (ultrasound investigations, radioimmunoassay, diagnostic puncture, thyroid lymphography) which are characterized by minimum dose formation, sufficient simplicity, reliability, low cost, a possibility to be widely employed in clinical practice, and safety. The 3rd level (scanning, endoscopy, angiography, CT, NMR) depends on the availability of expensive equipment employed in specialized clinical and diagnostic centers. The proposed algorithms of investigation can be changed in case of the appearance of new more informative and efficient diagnostic methods.

Algorithms↗
PubMed1987

Autoimmune thyroid disease: an expanding spectrum.

Autoimmune thyroid disease classically has included Hashimoto's thyroiditis and Graves' disease. Hashimoto's thyroiditis probably also includes focal thyroiditis, fibrous thyroiditis, primary myxedema, and Hashitoxicosis as variants. Graves' disease is associated with ophthalmopathy and dermopathy, and recent evidence suggests that these manifestations are autoimmune phenomena as well. Other associated autoimmune disorders include idiopathic thrombocytopenic purpura and antigen-antibody complex nephritis. Nonthyroid endocrine autoimmune deficiency disorders also have been classified as part of the spectrum of thyroid autoimmune disease. With the recent recognition of the spectrum of autoimmune mechanisms and antibody types and methods to distinguish antibody functions or types, our understanding of postpartum and neonatal thyroid disorders has been advanced considerably. The spectrum of neonatal thyroid disorders in the infants of women with autoimmune disease relates to the levels and types of antithyroid antibodies acquired from the mother. Finally, there is suggestive evidence that nonspecific goiter, including simple adolescent goiter and multinodular goiter as well as some cases of sporadic cretinism, may be part of an even more expanded spectrum of autoimmune thyroid disease.

Autoimmune Diseases↗
PubMed2003

Autoimmune thyroid disease: propagation and progression.

Autoimmune thyroid disease is the archetype for organ-specific autoimmune disorders. Progress in treating these disorders lies in improvements of our understanding of the predisposing factors responsible, the mechanisms responsible for progression of disease, and the interaction between thyroid antigens and the immune system at the level of the T cell and antibody. In common with other autoimmune diseases, genetic, environmental and endogenous factors are required in an appropriate combination to initiate thyroid autoimmunity. At present the only genetic factors which have been confirmed lie in the HLA complex and CTLA-4 or a closely linked gene. Identifying other predisposing genes will require large-scale family studies, or further insights into likely candidate genes. A number of environmental factors are known to predispose to autoimmune thyroid disease, including smoking, stress and iodine intake, while immunomodulatory treatments are revealing new pathways for disease emergence. The thyroid cell itself appears to play a major role in disease progression, interacting with the immune system through expression of a number of immunologically active molecules including HLA class I and II, adhesion molecules, cytokines, CD40 and complement regulatory proteins. New techniques, in particular phage display libraries, are providing the methods with which to identify autoantibody diversity in autoimmune thyroid disease and to provide tools for mapping autoantigenic epitopes. Application of these techniques is likely to lead to an understanding of how TSH receptor antibodies interact with the receptor to cause Graves' disease and also to the identification of novel orbital autoantigens in thyroid-associated ophthalmopathy.

Disease Progression↗
PubMed1989

[Scleroderma and thyroid diseases].

The authors report a prospective study of the thyroid function of 18 consecutive patients with systemic scleroderma and 7 patients with morphea. A history was taken and patients were examined for thyroid disease. The patients were tested for free thyroxin, TSH, cholesterolemia, circulating TeBG, anti-microsomial and anti-thyroglobulin antibodies and had a TRH test. The incidence of thyroid diseases was correlated with an age and sex-matched control population consisting of 2,534 subjects of the Loire department. None of the patients with morphea had a history of thyroid pathology and the thyroid screenings were within normal limits. A familial history of thyroid disease was found in 7 out of 18 patients with systemic scleroderma, and 8 out of 18 patients had a thyreopathy (one Hashimoto's disease, one Graves' disease, one toxic adenoma, one hypothyroidism, two euthyroid goiters, two nodular thyroids). The TRH test only revealed a toxic adenoma. A thyroid disease preceded systemic scleroderma in 5 out of 18 cases with delays ranging from 1 to 38 years. In 3 cases, the thyroid disease occurred within two years after the onset of systemic scleroderma. The prevalence of thyroid disease was significantly higher than in a comparable population sample of subjects from the same geographic region (p less than 0.01). The authors review the literature and discuss the physiopathologic relationships between the two clinical entities. The authors suggest to perform a thyroid screening (ultrasensitive TSH assay) on all patients with systemic sclerosis and especially on those whose clinical follow-up is atypical and on those with a familial and/or personal history of thyroid disease.

Aged↗
PubMed2001

Histocompatibility leucocyte antigens and closely linked immunomodulatory genes in autoimmune thyroid disease.

OBJECTIVES: Associations between autoimmune thyroid disease and antigens of the major histocompatibility complex (MHC) have long been recognized. Graves' disease (GD) is associated with the histocompatibility leucocyte antigen (HLA) haplotype A*01-B*0801-DRB1*0301-DQA1*0501-DQB1*0201 (or B8/DR3) whereas autoimmune hypothyroidism (AIH) has been weakly associated with HLA DRB1*03, *04 and *11/*12 alleles (or DR3, DR4 and DR5). However, the presence of important immunoregulatory genes within the HLA Class II and III regions raises the possibility that these genes harbour the primary susceptibility locus. This study examines genetic variation across the MHC in UK Caucasoid subjects with autoimmune thyroid disease. PATIENTS AND METHODS: DNA extracted from venous blood samples from 215 patients with autoimmune thyroid disease (GD 135, AIH 77) and 267 control subjects was analysed. Genotyping was performed using polymerase chain reaction and sequence specific primers for HLA Class I and II alleles and polymorphisms within the TAP1, TAP2, tumour necrosis factor (TNF), lymphotoxin alpha (LTalpha), heat shock protein (HSP)70-1, HSP70-2 and HSP70-Hom genes. RESULTS: For GD, the strongest association was with DRB1*03 [56% patients positive vs. 24% controls, P = 2 x 10(-10), odds ratio (OR) 4.0]. Positive associations were also seen for DRB1*03 linked alleles, B*0801, DRB3*01/02, DQA1*05, DQB1*02 and DPB1*0101 (OR 2.3-3.4). Specific TNF and LTalpha alleles were strongly associated with GD (Pc = 3 x 10(-5) and 0.001) and weak associations were seen for HSP70-1 + 190C and HSP70-2 + 1267G polymorphisms (Pc = 0.05 and 0.01). These associations were not significant when DRB1*03 status was considered. Patients with AIH showed only a weak association with DQB1*03 (P = 0.02). CONCLUSIONS: These results show that, of the polymorphisms tested within the MHC, GD is most strongly associated with DRB1*03, and associations with other immunoregulatory genes previously described in Caucasian subjects most likely reflect linkage disequilibrium. AIH differs from GD, being less influenced by the MHC region.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Clinical perspectives in the diagnosis of thyroid disease.

BACKGROUND: The wide array of available thyroid diagnostic tests can help provide accurate diagnoses for most cases of thyroid disease but can be confusing and costly when used inappropriately. METHODS: Published articles were reviewed and combined with the author's clinical experience and data collected from patients. RESULTS: The discussions focus on confusing aspects of thyroid diagnostic tests, the use and limitations of the thyrotropin test to screen for thyroid dysfunction, biological factors that complicate the interpretation of this and other thyroid diagnostic tests, and a combined clinical and laboratory approach to (a) thyroid diseases with only one important dimension ("simplex" conditions) and (b) thyroid diseases with several important dimensions ("multiplex" conditions). CONCLUSION: The optimal use of thyroid diagnostic tests is patient-specific and depends on the patient's specific thyroid disease, the stage of disease, and coexisting medical conditions.

Clinical Laboratory Techniques↗
PubMed1988

Needle biopsy of nodular thyroid disease.

To evaluate nodular thyroid disease, 150 patients underwent 169 fine needle biopsies (FNB) and recently 28 have also had core needle biopsies (CNB). Multiple biopsies were required in 19 patients because of multiple lesions, reaccumulation of cysts, follow-up of nodules failing to regress, or inadequate material. Adequate material was obtained in 97 per cent of FNB and 92 per cent of CNB. FNB and CNB agreed in 20 of 28 cases. There were no complications with FNB and one patient (4%) hemorrhaged with CNB. Forty nine patients underwent thyroidectomy. Postoperative diagnoses include papillary carcinoma (9), follicular carcinoma (2), lymphoma (2), medullary carcinoma (1), metastatic carcinoma (1), benign nodular goiter (14), follicular neoplasm (15), and thyroiditis (5). Sixty per cent of patients avoided surgery, 61 per cent of operated specimens contained neoplasia and 31 per cent contained malignancy. Eighty seven per cent of malignancies were identified at the initial evaluation. FNB had 86 per cent sensitivity for neoplasia and 44 per cent specificity for neoplasm (94% for papillary carcinoma). CNB had 89 per cent sensitivity and 67 per cent specificity for neoplasm. FNB and CNB are useful means of assessing thyroid nodules for the presence of cancer. They can decrease the need for diagnostic thyroidectomy. However, clinical evaluation must still be used in conjunction when determining the need for thyroidectomy.

Biopsy, Needle↗
PubMed1988

Radiation and thyroid disease.

External irradiation of the thyroid causes the subsequent development of thyroid malignancies at an approximate rate of 5 per rad per million people per year. There is no certain lower threshold, but possibly doses above 3000 rads are less effective. The tumours produced are primarily differentiated malignancies typical of non-irradiated patients, and the clinical course is similar. Most radiation-associated malignancies followed treatment given for enlarged thymic glands, enlargement of the tonsils or adenoids, and acne. Currently patients are seen with radiation-associated thyroid disease following treatment of malignant tumours in the neck. Diagnostic manoeuvres are similar to those used in non-irradiated individuals, but multinodularity is probably an indication for operation. Because of the high incidence of multicentricity, we prefer near-total thyroidectomy if cancer is found. Prophylactic thyroid hormone administration is of uncertain value in preventing the development of tumours. X-ray to the thyroid also can induce other histologic abnormalities, including a high incidence of adenomas and hypothyroidism, and is associated with an increased incidence of autoimmune thyroid disease and possibly the development of exophthalmos and Graves' disease. In contrast to the obvious effects of external irradiation, 131I diagnostic tests and treatments have not been associated with a clearly increased incidence of thyroid malignancy.

Humans↗
PubMed2005

Thyroid disease and increased cardiovascular risk.

The effects of thyroid dysfunction are thought to be reversible on restoration of euthyroidism, but postmortem and epidemiologic data suggest that subclinical or treated thyroid disease is associated with increased vascular risk. In order to determine the extent of this risk, and to explore whether the nature and/or treatment of thyroid disease are critical in this relationship, we used medical record linkage to match patients with treated thyroid disease of various etiologies with routinely collected national inpatient and daycase hospital discharge records and death records, and assessed the number of hospitalizations from cardiovascular or cerebrovascular disease or death in patients with thyroid disease and control patients. Patients treated for Graves' disease had more hospitalizations from cardiovascular disease than controls (relative risk, 1.42; 95% confidence interval, 1.20 to 1.67; p < 0.001). Toxic multinodular goiter was also associated with significantly higher rates of cardiovascular disease (relative risk, 1.50; 95% confidence interval, 1.11 to 2.02; p = 0.008). Patients with Hashimoto's thyroiditis aged over 50 years had a threefold increase in cardiovascular admissions compared to controls (23.5% and 6.5%, respectively; 95% confidence interval for difference, 6.0% to 27.9%; p = 0.003). Thus, different forms of thyroid disease were associated with increased long-term vascular risk despite restoration of euthyroidism. The mechanisms that mediate this risk are unclear but may not involve thyroid hormone abnormality.

Adult↗
PubMed2005

Significant clinical differences in primary hyperparathyroidism between patients with and those without concomitant thyroid disease.

PURPOSE: We evaluated the differences in diagnosis and treatment for primary hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid disease. METHODS: One hundred and ten patients with pHPT underwent parathyroid localization and thyroid examination by ultrasonography (US) and sestamibi scintigraphy (MIBI). The clinical and biochemical findings, parathyroid localization, and operations performed were compared in 49 patients without thyroid disease and 61 patients with thyroid disease. RESULTS: Asymptomatic hypercalcemia was significantly more prevalent in patients with concomitant thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P < 0.01). The mean serum calcium was significantly higher and the inorganic phosphate level was significantly lower in patients without concomitant thyroid disease than in those with concomitant thyroid disease (P < 0.05, P < 0.01, respectively). The pathologic parathyroid gland was identified significantly more often in patients without concomitant thyroid disease than in those with concomitant thyroid disease both by US and MIBI (P < 0.05). Unilateral exploration was performed more often in patients without thyroid disease than in those with thyroid disease (P < 0.01). CONCLUSION: Primary hyperparathyroidism was diagnosed at an earlier stage in patients with concomitant thyroid disease. Thyroid disease concomitant with pHPT influenced parathyroid localization as well as the indication for minimally invasive parathyroidectomy.

Adult↗