Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report.

PubMed

Marzuillo, Pierluigi; Grandone, Anna; Perrotta, Silverio; Ruggiero, Laura; Capristo, Carlo; Luongo, Caterina; Miraglia Del Giudice, Emanuele; Perrone, Laura

2016-06-18

In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation. A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months. Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.

Immunological Mechanisms Implicated in the Pathogenesis of Chronic Urticaria and Hashimoto Thyroiditis.

PubMed

Berghi, Nicolae Ovidiu

2017-08-01

Autoimmunity represents the attack of the immune system of an organism against its own cells and tissues. Autoimmune diseases may affect one organ (Hashimoto thyroiditis) or can be systemic (chronic urticaria). Many factors are implicated in the pathogenesis of autoimmunity (white cells, cytokines, chemokines). Hashimoto thyroiditis has been associated with chronic urticaria in the last 3 decades in a number of clinical studies. Anti-thyroid antibodies have been documented in a proportion ranging from 10% to 30% in chronic urticaria patients in different countries from 3 continents. Two of the factors involved in the mechanism of autoimmunity are present both in the pathophysiology of Hashimoto thyroiditis and chronic urticaria. According to recent studies, IL6 is implicated in the pathogenesis of both diseases. TregsCD4+CD25+Foxp3+ cells have also been implicated in the pathological mechanisms of these 2 entities. This review offers an explanation of the clinical and statistical association between these two diseases from the pathophysiological point of view.

Thyroid Autoimmunity in Girls with Turner Syndrome.

PubMed

Witkowska-Sędek, Ewelina; Borowiec, Ada; Kucharska, Anna; Chacewicz, Karolina; Rumińska, Małgorzata; Demkow, Urszula; Pyrżak, Beata

2017-01-01

Turner syndrome is associated with increased incidence of autoimmune diseases, especially those of the thyroid gland. The aim of this study was to assess the prevalence of thyroid autoimmunity among pediatric patients with Turner syndrome. The study was retrospective and included 41 girls with Turner syndrome aged 6-18 years. Free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO-Ab) antibodies, anti-thyroglobulin (TG-Ab) antibodies, and karyotype were investigated. The correlation between karyotype and incidence of thyroid autoimmunity was also examined. Eleven patients (26.8%) were positive for TPO-Ab and/or TG-Ab. Three girls from that subgroup were euthyroid, 5 had subclinical hypothyroidism, and 3 were diagnosed with overt hypothyroidism. Out of these 11 patients affected by thyroid autoimmunity, 6 girls had mosaic karyotype with X-isochromosome (n = 4) or with deletions (n = 2), and 5 had the 45,X karyotype. The study findings confirmed a high incidence of thyroid autoimmunity in girls with Turner syndrome, but we failed to observe an association between the incidence of thyroid autoimmunity and karyotype. We conclude that it is important to monitor thyroid function in patients with Turner syndrome because they are prone to develop hypothyroidism.

The Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease.

PubMed

Norström, Fredrik; van der Pals, Maria; Myléus, Anna; Hammarroth, Solveig; Högberg, Lotta; Isaksson, Anders; Ivarsson, Anneli; Carlsson, Annelie

2018-01-25

Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. However, data are lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1,695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid stimulating hormone and free thyroxine. TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were: 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicate that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

Thyroid consequences of the Chernobyl nuclear accident.

PubMed

Pacini, F; Vorontsova, T; Molinaro, E; Shavrova, E; Agate, L; Kuchinskaya, E; Elisei, R; Demidchik, E P; Pinchera, A

1999-12-01

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid antibodies not associated with significant thyroid dysfunction. This finding is consistent with the short period of follow-up, but it is highly likely that these children will develop clinical thyroid autoimmune diseases in the future. Therefore, screening programmes for this at-risk population should focus, not only on the detection of thyroid nodules and cancer, but also on the development of thyroid autoimmune diseases.

Clinic-cytologic study of conjunctivochalasis and its relation to thyroid autoimmune diseases: prospective cohort study.

PubMed

de Almeida, Sandra Flavia Fiorentini; de Sousa, Luciene B; Vieira, Luis A; Chiamollera, Maria I; Barros, Jeison de N

2006-08-01

To determine the prevalence of conjunctivochalasis in patients with immune thyroid diseases, to determine whether there is any association between the 2 diseases, and to determine cytologic study of conjunctivochalasis through the cytology impression test. A clinical prospective cohort study carried out by the External Diseases Department in the Ophthalmology Sector and the Thyroid Department in the Endocrinology Sector at Federal University of Sao Paulo (UNIFESP). The patients included were divided into 2 groups following these inclusion criteria: a control group of 25 patients without thyroid diseases, confirmed after clinical and laboratory examinations (thyroid hormones), or any other ocular diseases. The study group consisted of 31 patients with thyroid diseases, the diagnosis of which was confirmed by the Endocrinology Sector. The thyroidopathies included were autoimmune diseases but excluded nonautoimmune diseases. A protocol endorsed by the UNIFESP was followed, using clinical and ophthalmological history, biomicroscopy, and impression cytology. Fifty-two percent of patients without thyroid diseases and 88% of patients with thyroid diseases presented with conjunctivochalasis. The risk ratio was 1.705 (Pr > chi(2) = 0.0038), indicating that there is an association between them. For the impression cytology in inferior bulbar conjunctiva, there was an association between the result of the impression cytology and conjunctivochalasis (Pearson chi(2) = 10.1190 Pr = 0.006). The prevalence of conjunctivochalasis in patients with autoimmune thyroid diseases was 88%. Patients with autoimmune thyroidopathy presented higher percentages of conjunctivochalasis than the control group, confirming the association between them. The cytologic study showed the highest prevalence of abnormal surface features in eyes with conjunctivochalasis.

Autoimmune Thyroid Disorders

PubMed Central

Iddah, M. A.; Macharia, B. N.

2013-01-01

Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice. PMID:23878745

Real-time shear wave elastography may predict autoimmune thyroid disease.

PubMed

Vlad, Mihaela; Golu, Ioana; Bota, Simona; Vlad, Adrian; Timar, Bogdan; Timar, Romulus; Sporea, Ioan

2015-05-01

To evaluate and compare the values of the elasticity index as measured by shear wave elastography in healthy subjects and in patients with autoimmune thyroid disease, in order to establish if this investigation can predict the occurrence of autoimmune thyroid disease. A total of 104 cases were included in the study group: 91 women (87.5%), out of which 52 (50%) with autoimmune thyroid disease diagnosed by specific tests and 52 (50%) healthy volunteers, matched for age and gender. For all the subjects, three measurements were performed on each thyroid lobe and a mean value was calculated. The data were expressed in kPa. The investigation was performed with an Aixplorer system (SuperSonic Imagine, France), using a linear high-resolution 15-4 MHz transducer. The mean value for the elasticity index was similar in the right and the left thyroid lobes, both in normal subjects and in patients with autoimmune thyroid disease: 19.6 ± 6.6 vs. 19.5 ± 6.8 kPa, p = 0.92, and 26.6 ± 10.0 vs. 25.8 ± 11.7 kPa, p = 0.71, respectively. This parameter was significantly higher in patients with autoimmune thyroid disease than in controls (p < 0.001). For a cut-off value of 22.3 kPa, which resulted in the highest sum of sensitivity and specificity, the elasticity index assessed by shear wave elastography had a sensitivity of 59.6% and a specificity of 76.9% (AUROC = 0.71; p < 0.001) for predicting the presence of autoimmune thyroid disease. Quantitative elasticity index measured by shear wave elastography was significantly higher in autoimmune thyroid disease than in normal thyroid parenchyma and may predict the presence of autoimmune thyroid disease.

Autoimmune hyperthyroidism due to secondary adrenal insufficiency: resolution with glucocorticoids.

PubMed

Skamagas, Maria; Geer, Eliza B

2011-01-01

To describe the course of autoimmune hyperthyroid disease in a patient with corticotropin (ACTH) deficiency treated with glucocorticoids. We report the clinical presentation, laboratory data, imaging studies, and management of a patient with weight loss, fatigue, apathy, hallucinations, and arthritis. Autoimmune hyperthyroidism (positive thyroperoxidase and thyroglobulin antibodies and borderline positive thyrotropin receptor antibody) was diagnosed in a 71-year-old woman. New psychotic symptoms prompted brain magnetic resonance imaging, which revealed a partially empty sella. Undetectable morning cortisol, undetectable ACTH, and failure to stimulate cortisol with synthetic ACTH (cosyntropin 250 mcg) secured the diagnosis of long-standing secondary adrenal insufficiency. Hydrocortisone replacement improved the patient's symptoms, resolved the thyroid disease, and decreased thyroid antibody titers. In retrospect, the patient recalled severe postpartum hemorrhage requiring blood transfusion at age 38 years. A Sheehan event probably occurred 33 years before the patient presented with corticotropin deficiency. Hyperthyroidism accelerated cortisol metabolism and provoked symptoms of adrenal insufficiency. The hypocortisolemic state may precipitate hyperimmunity and autoimmune thyroid disease. Rapid resolution of hyperthyroidism and decreased thyroid antibody titers with glucocorticoid treatment support this hypothesis.

Thyroid storm and warm autoimmune hemolytic anemia.

PubMed

Moore, Joseph A; Gliga, Louise; Nagalla, Srikanth

2017-08-01

Graves' disease is often associated with other autoimmune disorders, including rare associations with autoimmune hemolytic anemia (AIHA). We describe a unique presentation of thyroid storm and warm AIHA diagnosed concurrently in a young female with hyperthyroidism. The patient presented with nausea, vomiting, diarrhea and altered mental status. Laboratory studies revealed hemoglobin 3.9g/dL, platelets 171×10 9 L -1 , haptoglobin <5mg/dL, reticulocytosis, and positive direct antiglobulin test (IgG, C3d, warm). Additional workup revealed serum thyroid stimulating hormone (TSH) <0.01μIU/mL and serum free-T4 (FT4) level 7.8ng/dL. Our patient was diagnosed with concurrent thyroid storm and warm AIHA. She was started on glucocorticoids to treat both warm AIHA and thyroid storm, as well as antithyroid medications, propranolol and folic acid. Due to profound anemia and hemodynamic instability, the patient was transfused two units of uncrossmatched packed red blood cells slowly and tolerated this well. She was discharged on methimazole as well as a prolonged prednisone taper, and achieved complete resolution of the thyrotoxicosis and anemia at one month. Hyperthyroidism can affect all three blood cell lineages of the hematopoietic system. Anemia can be seen in 10-20% of patients with thyrotoxicosis. Several autoimmune processes can lead to anemia in Graves' disease, including pernicious anemia, celiac disease, and warm AIHA. This case illustrates a rarely described presentation of a patient with Graves' disease presenting with concurrent thyroid storm and warm AIHA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical Value of Thyrotropin Receptor Antibodies for the Differential Diagnosis of Interferon Induced Thyroiditis.

PubMed

Benaiges, D; Garcia-Retortillo, M; Mas, A; Cañete, N; Broquetas, T; Puigvehi, M; Chillarón, J J; Flores-Le Roux, J A; Sagarra, E; Cabrero, B; Zaffalon, D; Solà, R; Pedro-Botet, J; Carrión, J A

2016-01-01

The clinical value of thyrotropin receptor antibodies for the differential diagnosis of thyrotoxicosis induced by pegylated interferon-alpha remains unknown. We analyzed the diagnostic accuracy of thyrotropin receptor antibodies in the differential diagnosis of thyrotoxicosis in patients with chronic hepatitis C (CHC) receiving pegylated interferon-alpha plus ribavirin. Retrospective analysis of 274 patients with CHC receiving pegylated interferon-alpha plus ribavirin. Interferon-induced thyrotoxicosis was classified according to clinical guidelines as Graves disease, autoimmune and non- autoimmune destructive thyroiditis. 48 (17.5%) patients developed hypothyroidism, 17 (6.2%) thyrotoxicosis (6 non- autoimmune destructive thyroiditis, 8 autoimmune destructive thyroiditis and 3 Graves disease) and 22 "de novo" thyrotropin receptor antibodies (all Graves disease, 2 of the 8 autoimmune destructive thyroiditis and 17 with normal thyroid function). The sensitivity and specificity of thyrotropin receptor antibodies for Graves disease diagnosis in patients with thyrotoxicosis were 100 and 85%, respectively. Patients with destructive thyroiditis developed hypothyroidism in 87.5% of autoimmune cases and in none of those with a non- autoimmune etiology (p<0.001). Thyrotropin receptor antibodies determination cannot replace thyroid scintigraphy for the differential diagnosis of thyrotoxicosis in CHC patients treated with pegylated interferon. © Georg Thieme Verlag KG Stuttgart · New York.

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study

PubMed Central

Zulfiqar, AA; Andres, E

2017-01-01

Objective: To investigate the association between pernicious anemia and other autoimmune diseases. Methods: This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. Results: A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. Conclusion: We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b. PMID:29362601

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study.

PubMed

Zulfiqar, A A; Andres, E

2017-01-01

To investigate the association between pernicious anemia and other autoimmune diseases. This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

The immune system which adversely alter thyroid functions: a review on the concept of autoimmunity.

PubMed

Mansourian, Azad Reza

2010-08-15

The immune system protect individual from many pathogens exists within our environment and in human body, by destroying them through molecular and cellular mechanism of B and T cells of immune system. Autoimmunity is an adverse relation of immune system against non- foreign substances leaving behind either alters the normal function or destroying the tissue involved. Autoimmunity occur in genetically predispose persons with familial connections. The autoimmunity to the thyroid gland mainly consists of Hashimato thyroiditis and Grave's disease, the two end of spectrum in thyroid function of hypo and hyperactivity, respectively. The thyroid stimulating hormone receptor, thyroglobuline, enzymes of thyroid hormones synthesis are targeted by autoantibodies and cell- mediated reactions. The aim of this review is to explore the studies reported on the autoimmunity to the thyroid gland.

Thyroid autoimmunity and function among Ugandan children and adolescents with type-1 diabetes mellitus.

PubMed

Muhame, Rugambwa Michael; Mworozi, Edison Arwanire; McAssey, Karen; Lubega, Irene

2014-01-01

Up to 30% of type-1 diabetes mellitus (T1DM) patients have co-existent thyroid autoimmunity with up to 50% of them having associated thyroid dysfunction. Routine screening for thyroid autoimmunity and dysfunction is recommended in all T1DM patients. However, this was not currently practiced in Ugandan paediatric diabetes clinics. There was also paucity of data regarding thyroid autoimmunity and dysfunction in African children and adolescents with diabetes mellitus. The objective of this study was to quantify the magnitude of thyroid autoimmunity and dysfunction in Ugandan children with TIDM. This was a cross sectional descriptive study to determine the prevalence of thyroid autoantibodies and describe thyroid function among children and adolescents aged 1-19 years with diabetes mellitus attending the paediatric diabetes clinic at Mulago National Referral Hospital, Kampala, Uganda. Following enrollment, we obtained details of clinical history and performed physical examination. Blood (plasma) was assayed to determine levels of antibodies to thyroid peroxidase (antiTPO), free thyroxine (FT4) and thyrotropin (TSH). The prevalence of thyroid autoimmunity was 7.3% (5/69). All antiTPO positive subjects were post pubertal, aged between 13-17 years with females comprising 3/5 of the antiTPO positive subjects. All study subjects were clinically euthyroid; however, 7.3% (5/69) of the study subjects had subclinical hypothyroidism. These data strengthen the argument for routine screening of all diabetic children and adolescents for thyroid autoimmunity (particularly anti-TPO) as recommended by international guidelines. We also recommend evaluation of thyroid function in diabetic children and adolescents to minimize the risk of undiagnosed thyroid dysfunction.

Thyroid dysfunction and thyroid autoimmunity in euthyroid women in achieving fertility.

PubMed

Medenica, S; Nedeljkovic, O; Radojevic, N; Stojkovic, M; Trbojevic, B; Pajovic, B

2015-01-01

Thyroid disease is the second most common endocrine condition in women of childbearing age. Thyroid hormones are involved in control of menstrual cycle and in achieving fertility affecting the actions of follicle-stimulating hormone and luteinizing hormone on steroid biosynthesis by specific triiodothyronine sites on oocytes; therefore, affect all aspects of reproduction. It remains controversial if pregnant women should be screened for thyroid dysfunction. Purpose of this review was to examine recent studies on the assessment of thyroid dysfunction in pregnancy, its treatment and newly perspective of thyroid autoimmunity in pregnant euthyroid women in achieving fertility. An electronic search was conducted using the internet medical databases: Medline/PubMed, EMBASE, EBSCO, and the Cochrane library. Thyroid gland faces great challenge in pregnancy when many hormonal changes occur. Precondition for normal follicular development and ovulation is pulsate gonadothropin realizing hormone secretion. Thyroid dysfunction in pregnancy is classified as forms of hypothyroidism (positivity of thyroid autoantibody, isolated hypothyroidism, and subclinical or overt hypothyroidism), hyperthyroidism, and autoimmune disease, but also thyroid nodules and cancer, iodine insufficiency and postpartum thyroiditis. These conditions can cause adverse effects on mother and fetus including pregnancy loss, gestational hypertension, or pre-eclampsia, pre-term delivery, low birth weight, placental abruption and postpartum hemorrhage. There is an evidence that thyroid autoimmunity, in thyroid dysfunction adversely affects conception and pregnancy outcomes, but it is unclear what impact has isolated eumetabolic thyroid autoimmunity in achieving fertility, especially in women undergoing in vitro fertilization. Treatment of euthyroid pregnant women with positive thyroid peroxides antibodies is still controverse, but not few studies show that levothyroxine substitution is able to lower the chance of miscarriage and premature delivery. Further randomized trials are needed to expand our knowledge of physiologic changes in thyroid function during the pregnancy and to reveal mechanisms by which thyroid autoimmunity in euthyroid women affect fertility, especially the success of assisted reproductive technology in achieving the same and validity of levothyroxine administration in thyroid autoimmunity positive women.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders.

PubMed

Ordookhani, Arash; Burman, Kenneth D

2017-04-01

There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders

PubMed Central

Ordookhani, Arash; Burman, Kenneth D.

2017-01-01

Context There are contradictory results on the effect of hypothyroidism on the changes in hemostasis. Inadequate population-based studies limited their clinical implications, mainly on the risk of venous thromboembolism (VTE). This paper reviews the studies on laboratory and population-based findings regarding hemostatic changes and risk of VTE in hypothyroidism and autoimmune thyroid disorders. Evidence Acquisition A comprehensive literature search was conducted employing MEDLINE database. The following words were used for the search: Hypothyroidism; thyroiditis, autoimmune; blood coagulation factors; blood coagulation tests; hemostasis, blood coagulation disorders; thyroid hormones; myxedema; venous thromboembolism; fibrinolysis, receptors thyroid hormone. The papers that were related to hypothyroidism and autoimmune thyroid disorder and hemostasis are used in this review. Results Overt hypothyroidism is more associated with a hypocoagulable state. Decreased platelet count, aggregation and agglutination, von Willebrand factor antigen and activity, several coagulation factors such as factor VIII, IX, XI, VII, and plasminogen activator-1 are detected in overt hypothyrodism. Increased fibrinogen has been detected in subclinical hypothyroidism and autoimmune thyroid disease rendering a tendency towards a hypercoagulability state. Increased factor VII and its activity, and plasminogen activator inhibitor-1 are among several findings contributing to a prothrombotic state in subclinical hypothyroidism. Conclusions Overt hypothyroidism is associated with a hypocoagulable state and subclinical hypothyroidism and autoimmune thyroid disorders may induce a prothrombotic state. However, there are contradictory findings for the abovementioned thyroid disorders. Prospective studies on the risk of VTE in various levels of hypofunctioning of the thyroid and autoimmune thyroid disorders are warranted. PMID:29026409

Age impact on autoimmune thyroid disease in females

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

Differential expression of connexin 43 in human autoimmune thyroid disease.

PubMed

Jiang, Xiao-Yan; Feng, Xiao-Hong; Li, Guo-Yan; Zhao, Qian; Yin, Hui-Qing

2010-05-01

Gap junctions provide a pathway for cell-to-cell communication. Reduced thyroid epithelial cell-cell communication has been reported in some animal models of autoimmune thyroid disease. In order to assess whether this change was similar to human autoimmune thyroid disease, we identified some connexin proteins and their corresponding mRNA in human thyroid gland. The aim of our study was to explore the expression of connexin 43 (Cx43) in the thyroid gland from normal and diseased human thyroid tissue by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). The expression levels of Cx43 in Grave's disease were significantly increased in comparison with those of normal thyroid tissue. There was a significant decrease in expression of Cx43 in Hashimoto's thyroiditis, compared with normal thyroid tissue. These data indicate that changes of Cx43 expression in human autoimmune thyroid disease were associated with variations in thyroid function and hormone secretion. 2009 Elsevier GmbH. All rights reserved.

Conversion of autoimmune hypothyroidism to hyperthyroidism

PubMed Central

2014-01-01

Background Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. Case presentation We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. Conclusion High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone. PMID:25086829

Thyroid autoimmunity in bipolar disorder: A systematic review.

PubMed

Barbuti, Margherita; Carvalho, André F; Köhler, Cristiano A; Murru, Andrea; Verdolini, Norma; Guiso, Giovanni; Samalin, Ludovic; Maes, Michael; Stubbs, Brendon; Perugi, Giulio; Vieta, Eduard; Pacchiarotti, Isabella

2017-10-15

Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. The samples, study design and outcomes were heterogeneous. Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of autoimmune thyroid disease in melasma.

PubMed

Rostami Mogaddam, Majid; Iranparvar Alamdari, Manouchehr; Maleki, Nasrollah; Safavi Ardabili, Nastaran; Abedkouhi, Selma

2015-06-01

Melasma is one of the most frequently acquired hyperpigmentation disorders clinically characterized by symmetrical brown patches on sun-exposed areas. To date, few studies have been conducted about the relationship between thyroid autoimmun-ity and melasma. To evaluate the thyroid dysfunction and autoimmunity in nonpregnant women with melasma. A total of 70 women with melasma and 70 age-matched healthy women with no history of melasma were enrolled in the study. We studied the thyroid hormone profile in both groups. The statistical analysis was performed using SPSS software. Patients with melasma had 18.5% frequency of thyroid disorders, and 15.7% had positive anti-TPO, while subjects from the control group had a 4.3% frequency of thyroid abnormalities, and only 5.7% had positive anti-TPO. There was a significantly higher prevalence of thyroid dysfunction in women with melasma compared with control group (P = 0.008). This study suggests that there is a relationship between thyroid autoimmunity and melasma. However, to make recommendations on screening for thyroid disease in patients with melasma, future research of good methodological quality is needed. © 2015 Wiley Periodicals, Inc.

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

PubMed Central

2014-01-01

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

Thyroid dysfunction: an autoimmune aspect.

PubMed

Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

2015-01-01

Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins.

A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders

PubMed Central

Gwizdek, Katarzyna; Michalski, Marek; Wojnicz, Romuald

2016-01-01

The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the Herpesviridae virus family. EBV infection can cause infectious mononucleosis (IM) in the lytic phase of EBV’s life cycle. Past EBV infection is associated with lymphomas, and may also result in certain allergic and autoimmune diseases. Although potential mechanisms of autoimmune diseases have not been clearly elucidated, both genetic and environmental factors, such as infectious agents, are considered to be responsible for their development. In addition, EBV modifies the host immune response. The worldwide prevalence of autoimmune diseases shows how common this pathogen is. Normally, the virus stays in the body and remains dormant throughout life. However, this is not always the case, and a serious EBV-related illness may develop later in life. This explains the chronic course of autoimmune diseases that is often accompanied by exacerbations of symptoms. Based on the present studies, EBV infection can cause autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), Sjögren’s syndrome, and autoimmune hepatitis. The EBV has also been reported in patients with autoimmune thyroid disorders. Although EBV is not the only agent responsible for the development of autoimmune thyroid diseases, it can be considered a contributory factor. PMID:27833448

A possible link between the Epstein-Barr virus infection and autoimmune thyroid disorders.

PubMed

Dittfeld, Anna; Gwizdek, Katarzyna; Michalski, Marek; Wojnicz, Romuald

2016-01-01

The Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a member of the Herpesviridae virus family. EBV infection can cause infectious mononucleosis (IM) in the lytic phase of EBV's life cycle. Past EBV infection is associated with lymphomas, and may also result in certain allergic and autoimmune diseases. Although potential mechanisms of autoimmune diseases have not been clearly elucidated, both genetic and environmental factors, such as infectious agents, are considered to be responsible for their development. In addition, EBV modifies the host immune response. The worldwide prevalence of autoimmune diseases shows how common this pathogen is. Normally, the virus stays in the body and remains dormant throughout life. However, this is not always the case, and a serious EBV-related illness may develop later in life. This explains the chronic course of autoimmune diseases that is often accompanied by exacerbations of symptoms. Based on the present studies, EBV infection can cause autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), Sjögren's syndrome, and autoimmune hepatitis. The EBV has also been reported in patients with autoimmune thyroid disorders. Although EBV is not the only agent responsible for the development of autoimmune thyroid diseases, it can be considered a contributory factor.

Melkersson-Rosenthal syndrome with Hashimoto thyroiditis in a 9-year-old girl: an autoimmune disorder.

PubMed

Lee, Yun-Jin; Cheon, Chong Kun; Yeon, Gyu Min; Kim, Young Mi; Nam, Sang Ook

2014-05-01

Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patient's symptoms had completely disappeared. The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity. Copyright © 2014 Elsevier Inc. All rights reserved.

Autoimmune mechanisms in pernicious anaemia & thyroid disease.

PubMed

Osborne, David; Sobczyńska-Malefora, Agata

2015-09-01

Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Skin findings in autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls.

PubMed

Takir, Mümtaz; Özlü, Emin; Köstek, Osman; Türkoğlu, Zafer; Mutlu, Hasan Hüseyin; Uzunçakmak, Tuğba Kevser; Akdeniz, Necmettin; Karadağ, Ayşe Serap

2017-06-12

Thyroid disorders are associated with a wide variety of skin disorders that respond to treatment of hormone imbalance in most cases and thus are of vital importance to dermatologists. This study aimed to evaluate skin findings associated with autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls. A total of 300 consecutive patients with either autoimmune (n = 173) or nonautoimmune (n = 127) thyroid disease and 100 healthy control subjects were included in this cross-sectional study. Data on patient demographics, thyroid function tests, and skin findings were recorded for patient and control groups. Compared to control subjects, patients had higher proportions in populations with alopecia (P < 0.001), nail thinning (P = 0.02), brittle nails (P = 0.001), pruritus (P < 0.001), diffuse hyperhidrosis (P = 0.01), flushing (P = 0.001), and xerosis (P < 0.001). Onycholysis (P = 0.02), yellow skin (P = 0.04), periorbital edema (P = 0.03), psoriasis (P = 0.001), and palmoplantar hyperkeratosis (P = 0.007) were significantly more common in patients with autoimmune than nonautoimmune thyroid disease. A significantly higher percentage of patients with autoimmune rather than nonautoimmune thyroid disease had overall skin findings (P = 0.03) among the hyperthyroid patients.Conclusions: Our findings indicate that the presence of skin findings in a majority of thyroid patients significantly differs for certain cutaneous manifestations with respect to controls, autoimmune etiology, and thyroid functional status.

High salt intake does not exacerbate murine autoimmune thyroiditis

PubMed Central

Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

2014-01-01

Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

[Sub-acute encephalopathy that responds to steroids without any evidence of autoimmune thyroid disease: a case of non-vasculitic autoimmune meningoencephalitis].

PubMed

López-Ariztegui, N; Lobato-Casado, P; Muñoz-Escudero, F; Polo-Martín, M; Montes-Gonzalo, M C; Alvarez-Tejerina, A

To report a case of sub-acute encephalopathy with all the extension study negative and with response to steroid therapy. The study involves a 22-year-old female with no relevant past history who presented symptoms of sub-acute encephalopathy consisting in behavioural disorders, generalised seizures and bradypsychia, which gradually progressed to a state of low-level consciousness. While she was in hospital all kinds of diagnostic tests were conducted, the results of which were either normal or negative; the electroencephalogram was repeatedly abnormal and detection of protein 14-3-3 in cerebrospinal fluid was positive. Empirical corticoid therapy was begun with clinical and electrophysiological improvements and the patient recovered completely without any sequelae. With no evidence of autoimmune thyroid disease, although non-specific autoimmunity was present, the patient was diagnosed as having non-vasculitic autoimmune meningoencephalitis.

Autoimmune Alternating Hypo- and Hyperthyroidism in Children

PubMed Central

Mathew, Revi P.; Moore, Daniel J.

2013-01-01

Two children presented with autoimmune alternating hypo- and hyperthyroidism related to the presence of blocking and stimulating thyroid antibodies. It was difficult to control their thyroid function adequately with an appropriate single drug regimen, and both children underwent total thyroidectomy with subsequent stable management with levothyroxine replacement therapy postsurgically. Although this phenomenon is well described in adults, this report is the first of such occurrence in children. The possible mechanism for the variation in the type of clinical presentation and options for management are discussed. PMID:21700620

Expression of immunoregulatory molecules by thyrocytes protects nonobese diabetic-H2h4 mice from developing autoimmune thyroiditis.

PubMed

Nakahara, Mami; Nagayama, Yuji; Saitoh, Ohki; Sogawa, Rintaro; Tone, Shigenobu; Abiru, Norio

2009-03-01

One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2(h4) mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 x 10(10) particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-gamma and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4(+)Foxp3(+) regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2(h4) mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases.

Familial clustering of juvenile thyroid autoimmunity: higher risk is conferred by human leukocyte antigen DR3-DQ2 and thyroid peroxidase antibody status in fathers.

PubMed

Segni, Maria; Pani, Michael A; Pasquino, Anna Maria; Badenhoop, Klaus

2002-08-01

Thyroid autoimmunity is one of the most common immune disorders in females, and its polygenic background remains to be elucidated. The human leukocyte antigen (HLA) DQ region of chromosome 6 has been shown to confer susceptibility to thyroid autoimmune disease. The aim of our present investigation was to determine whether the transmission of high risk HLA DQ to patients with thyroid autoimmunity differs when transmission is from fathers as opposed to when transmission is from mothers. We studied 91 juvenile patients with chronic lymphocytic thyroiditis (68 females and 23 males; mean age, 10.5 +/- 3.9 yr), 12 patients with Graves' disease (all females; mean age, 8.8 +/- 4.0 yr), 53 healthy siblings, and their parents for thyroid function, antibodies, ultrasound, and DNA typing for HLA DQ susceptibility alleles. We observed an increased rate of transmission for the DQA1*0501-DQB1*0201 (DQ2) haplotype [35 of 53 transmitted (66%); P = 0.02]. This allele was preferentially transmitted by fathers [21 of 27 (78%); P < 0.004], whereas the maternal DQ2 haplotypes were not transmitted more often than expected. Subsequently, families were stratified as follows according to the parental thyroid peroxidase antibody (TPOAb) status: no parent, only mothers, only fathers, and both parents positive. There was no significant maternal transmission disequilibrium in any subset, but the paternal HLA DQ2 was preferentially transmitted [11 of 14 cases (79%); P = 0.03] in the group of TPOAb-positive mothers, and we observed a similar trend in the group of TPOAb- positive fathers (P = 0.08). Also, the portion of offspring affected by Graves' disease was significantly higher in TPOAb-positive than in TPOAb-negative fathers (P < 0.02). In conclusion, our findings demonstrate a significant effect of paternal HLA DQ alleles as well as antibody status on susceptibility to thyroid autoimmune disease in juvenile patients.

Development of Grave's disease seven months after Hashimoto's thyroiditis: a rare occurrence.

PubMed

Bravo-Llerena, Wilfredo Eddy; Valderrabano-Wagner, Rodrigo J; Quevedo-Quevedo, Juan; Reyes-Ortiz, Luis M

2010-01-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two opposite poles in the spectrum of autoimmune thyroid disease. On one extreme, HT or Chronic Lymphocytic thyroiditis (CLT) courses, as its name implies, with lymphocytic infiltrates replacing thyroid follicles, resulting in a loss of hormone-producing cells and, thus, primary hypothyroidism. On the other extreme, GD is characterized by primary hyperthyroidism due to stimulating autoantibodies against thyroid-stimulating hormone receptors (TSHRs) localized on thyrocytes' membranes of intact thyroid follicles. The presence of HT after GD or the concomitant combination of these two autoimmune entities ending in HT-depending hypothyroid state is well known. However, occurrence of GD after primary hypothyroidism due to CLT is very rare since thyrocytes with their TSHRs are promptly lost. We report a case in which hyperthyroidism occurred seven months after presentation of primary hypothyroidism and discuss potential mechanisms involved.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

PubMed

Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

2018-04-19

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

Organ specificity in autoimmune diseases: thyroid and islet autoimmunity in alopecia areata.

PubMed

Noso, Shinsuke; Park, Choongyong; Babaya, Naru; Hiromine, Yoshihisa; Harada, Takeshi; Ito, Hiroyuki; Taketomo, Yasunori; Kanto, Kousei; Oiso, Naoki; Kawada, Akira; Suzuki, Tamio; Kawabata, Yumiko; Ikegami, Hiroshi

2015-05-01

Multiple autoimmune diseases, such as autoimmunity against the thyroid gland and pancreatic islets, are often observed in a single patient. Although alopecia areata (AA) is one of the most frequent organ-specific autoimmune diseases, the association of AA with other autoimmune diseases and the genetic basis of the association remain to be analyzed. The aim of this study was to clarify the similarities and differences in HLA and clinical characteristics of thyroid and islet autoimmunity in patients with AA. A total of 126 patients with AA were newly recruited. Anti-islet and antithyroid autoantibodies were tested, and genotypes of HLA genes were determined. Among the autoimmune diseases associated with AA, autoimmune thyroid disease was most frequent (10.0%), followed by vitiligo (2.7%) and rheumatoid arthritis (0.9%) but not type 1 diabetes (0.0%). The prevalence of thyroid-related autoantibodies in patients with AA was significantly higher than that in controls (TSH receptor antibody [TRAb]: 42.7% vs 1.2%, P = 1.6 × 10(-46); thyroid peroxidase antibody: 29.1% vs 11.6%; P = 1.7 × 10(-6)), whereas the prevalence of islet-related autoantibodies was comparable between patients with AA and control subjects. The frequency of DRB1*15:01-DQB1*06:02, a protective haplotype for type 1 diabetes, was significantly higher in TRAb-positive (12.8%, P = .0028, corrected P value [Pc] = .02) but not TRAb-negative (7.1%, not significant) patients with AA than in control subjects (4.5%). The frequency of DRB1*04:05-DQB1*04:01, a susceptible haplotype for type 1 diabetes, was significantly lower in patients with AA (TRAb-positive: 8.5%; TRAb-negative: 11.9%) than in those with type 1 diabetes (29.5%, Pc < .0003 and Pc < .0008, respectively). AA was associated with thyroid autoimmunity but not islet autoimmunity, which correlated with class II HLA haplotypes susceptible or resistant to each autoimmune disease.

[Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease].

PubMed

Milosević, Dragoslav P; Djurica, Snezana; Davidović, Mladen; Stević, Radmila; Rajić, Miodrag; Marković, Natasa

2005-10-01

Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

[Maternal autoimmune thyroid disease: relevance for the newborn].

PubMed

Temboury Molina, M Carmen; Rivero Martín, M José; de Juan Ruiz, Jesús; Ares Segura, Susana

2015-04-08

Autoimmune thyroid disease is amongst the most frequent endocrine disorders during pregnancy. It is associated with an increase in perinatal morbidity, congenital defects, neurological damage, fetal and neonatal thyroid dysfunction. Maternal thyroid hormones play a key role in child neurodevelopment. We aimed to evaluate the thyroid function and the clinical course of neonates born from mothers with autoimmune thyroid disease during the first months of life in order to define the follow-up. We monitored thyroid function and clinical status during the first months in 81 newborns of mothers with autoimmune thyroid disease; 16 had Graves disease and 65 autoimmune thyroiditis. A percentage of 4.93 newborns had congenital defects, and 8.64% neonates showed an increase in thyrotropin (TSH) (>9.5 μUI/mL 2 times) and required thyroxin within the first month of life. A 85.7% of these showed a negative newborn screening (due to a later increase of TSH). A higher TSH value in the newborn was related to an older age of the mother, higher levels of thyroid peroxidase (TPO) antibody during pregnancy and lower birth weight. A higher free thyroxine (FT4) value in the newborn was related to fewer days of life and mothers with Graves disease. We recommend the evaluation of TSH, T4 and TPO antibodies before 10 weeks in all pregnant women with follow-up if maternal thyroid autoimmunity or disorders is detected. It is also recommended to test children's serum TSH and FT4 at 48 h of life in newborns of mothers with autoimmune thyroid disease and repeat them between the 2nd and 4th week in children with TSH>6 μUI/mL. Careful endocrine follow-up is advised in pregnant women and children if hyperthyroidism is detected. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto

PubMed Central

Weetman, Anthony P

2013-01-01

Hakaru Hashimoto described 4 patients with a hitherto unknown cause for goitre, struma lymphomatosa, a century ago. He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. Although the cause of the lymphocytic infiltration was unknown to Hashimoto, we now know through the pioneering studies of N.R. Rose and E. Witebsky [J Immunol 1956;76:417–427] that this condition is the archetype for autoimmune destruction as a disease mechanism. In the last two decades in particular, there has been huge interest in unravelling the genetic basis for this and related autoimmune disorders. The list of polymorphisms associated with autoimmune thyroid disease grows each year, and in the case of vitiligo, which is frequently found in association with thyroid autoimmunity, we know that 27 separate susceptibility loci account for less than 20% of the heritability of this condition. Environmental and existential factors may turn out to be just as complex in number and in interactions. We can thus imagine a ‘Swiss cheese’ model for the causation of autoimmune thyroid disease, in which the effects of cumulative weaknesses line up – like the holes in slices of cheese – to allow the catastrophic event of autoimmune destruction to occur. PMID:24783026

Serum Anti-TPO and TPO Gene Polymorphism as a Predictive Factor for Hidden Autoimmune Thyroiditis in Patient with Bronchial Asthma and Allergic Rhinitis.

PubMed

El Shabrawy, Reham M; Atta, Amal H; Rashad, Nearmeen M

2016-01-01

Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones T3 and T4. Autoimmune thyroiditis is a common disorder affecting 10% of population worldwide. A key feature of autoimmune thyroiditis is the presence of anti TPO antibodies, and some mutation of the TPO gene. Association between autoimmune thyroiditis and other autoimmune disorders has been reported but little is known about association with allergic diseases. In this study, we aimed to evaluate frequency of hidden autoimmune thyroiditis among allergic patient and examine possible relationship between anti-TPO levels and polymorphism at the TPO gene A2173/C exon 12 and different types of allergens. The study included 50 adult Egyptian patients with allergic rhinitis and /or bronchial asthma and 50 controls. For each subject, thyroid stimulating hormone (TSH), thyroxin 4 (T4) and Triiodothyronine (T3) hormones were measured. Anti-thyroid peroxidase (anti-TPO) level was detected by ELISA; and TPO gene polymorphism 2173A>C exon 12 was analyzed using restriction fragment length polymorphism (RFLP). Skin prick test was done to assess allergic response in patients. Serum levels of T3, T4 and TSH did not show any statistical significant difference between patients and groups. However, mean serum anti-TPO level was statistically higher in patients than controls, and correlated positively with body mass index, age, diastolic blood pressure, suggesting higher prevalence of hidden autoimmune thyroiditis in allergic patients than in control group. 2173A>C Genotyping revealed that the frequency of C allele is increased in the patient group. C allele represents a risk factor with odds ratio of 2.37 (1.035-5.44) and a significant P value <0.05. It is concluded that TPO 2173A>C polymorphism may be considered as a risk factor for developing autoimmune thyroiditis in patients with allergic rhinitis and asthma and that these patients should regularly be checked for hidden thyroiditis. Copyright© by the Egyptian Association of Immunologists.

Thyroid Stimulating Hormone Receptor Antibodies in Thyroid Eye Disease-Methodology and Clinical Applications.

PubMed

Diana, Tanja; Kahaly, George J

2018-05-02

Thyroid stimulating hormone receptor antibodies (TSHR-Ab) cause autoimmune hyperthyroidism and are prevalent in patients with related thyroid eye disease (TED). To provide a historical perspective on TSHR-Ab and to present evidence-based recommendations for clinical contemporary use. The authors review the recent literature pertaining to TSHR-Ab in patients with TED and describe the various immunoassays currently used for detecting TSHR-Ab and their clinical applications. We provide a historical summary and description of the various methods used to detect TSHR-Ab, foremost, the functional TSHR-Ab. Increasing experimental and clinical data demonstrate the clinical usefulness of cell-based bioassays for measurements of functional TSHR-Ab in the diagnosis and management of patients with autoimmune TED and in the characterization of patients with autoimmune-induced hyperthyroidism and hypothyroidism. Thyroid stimulating hormone receptor antibodies, especially the functional stimulating antibodies, are sensitive, specific, and reproducible biomarkers for patients with autoimmune TED and correlate well with clinical disease activity and clinical severity. Unlike competitive-binding assays, bioassays have the advantage of indicating not only the presence of antibodies but also their functional activity and potency. Measurement of TSHR-Ab (especially stimulating antibodies) is a clinically useful tool for the management of patients with TED.

Thyroid nodules and thyroid autoimmunity in the context of environmental pollution.

PubMed

Benvenga, Salvatore; Antonelli, Alessandro; Vita, Roberto

2015-12-01

Evidence suggests that in most industrialized countries autoimmune disorders, including chronic lymphocytic thyroiditis, are increasing. This increase parallels the one regarding differentiated thyroid cancer, the increment of which is mainly due to the papillary histotype. A number of studies have pointed to an association between chronic lymphocytic thyroiditis and differentiated thyroid cancer. The upward trend of these two thyroid diseases is sustained by certain environmental factors, such as polluting substances acting as endocrine disrupting chemicals. Herein we will review the experimental and clinical literature that highlights the effects of environmental and occupational exposure to polluting chemicals in the development of autoimmune thyroid disease or differentiated thyroid cancer. Stakeholders, starting from policymarkers, should become more sensitive to the consequences for the thyroid resulting from exposure to EDC. Indeed, the economic burden resulting from such consequences has not been quantified thus far.

Recombinant Protein Production from TPO Gen Cloning and Expression for Early Detection of Autoimmune Thyroid Diseases

NASA Astrophysics Data System (ADS)

Aulanni'am, Aulanni'am; Kinasih Wuragil, Dyah; Wahono Soeatmadji, Djoko; Zulkarnain; Marhendra, Agung Pramana W.

2018-01-01

Autoimmune Thyroid Disease (AITD) is an autoimmune disease that has many clinical symptoms but is difficult to detect at the onset of disease progression. Most thyroid autoimmune disease patients are positive with high titre of thyroid autoantibodies, especially thyroid peroxidase (TPO). The detection AITD are still needed because these tests are extremely high cost and have not regularly been performed in most of clinical laboratories. In the past, we have explored the autoimmune disease marker and it has been developed as source of polyclonal antibodies from patient origin. In the current study, we develop recombinant protein which resulted from cloning and expression of TPO gene from normal person and AITD patients. This work flows involves: DNA isolation and PCR to obtain TPO gene from human blood, insertion of TPO gene to plasmid and transformation to E. coli BL21, Bacterial culture to obtain protein product, protein purification and product analysis. This products can use for application to immunochromatography based test. This work could achieved with the goal of producing autoimmune markers with a guaranteed quality, sensitive, specific and economically. So with the collaboration with industries these devices could be used for early detection. Keywords: recombinant protein, TPO gene, Autoimmune thyroid diseases (AITD)ction of the diseases in the community.

Autoimmune Abnormalities of Postpartum Thyroid Diseases

PubMed Central

Di Bari, Flavia; Granese, Roberta; Le Donne, Maria; Vita, Roberto; Benvenga, Salvatore

2017-01-01

The year following parturition is a critical time for the de novo appearance or exacerbation of autoimmune diseases, including autoimmune thyroid disease. The vast majority of postpartum thyroid disease consists of postpartum thyroiditis (PPT) and the minority by Graves’ disease and non-autoimmune thyroiditis. PPT has a worldwide prevalence ranging from 1 to 22% and averaging 5% based on a review published in 2012. Several factors confer risk for the development of PPT. Typically, the clinical course of PPT is characterized by three phases: thyrotoxic, hypothyroid, and euthyroid phase. Approximately half of PPT women will have permanent hypothyroidism. The best humoral marker for predictivity, already during the first trimester of gestation, is considered positivity for thyroperoxidase autoantibodies (TPOAb), though only one-third to half of such TPOAb-positive pregnant women will develop PPT. Nutraceuticals (such as selenium) or omega-3-fatty acid supplements seem to have a role in prevention of PPT. In a recent study on pregnant women with stable dietary habits, we found that the fish consumers had lower rates of positivity (and lower serum levels) of both TPOAb and thyroglobulin Ab compared to meat eaters. Finally, we remind the reader of other diseases that can be observed in the postpartum period, either autoimmune or non-autoimmune, thyroid or non-thyroid. PMID:28751877

Autoimmune thyrotoxicosis: diagnostic challenges.

PubMed

Ponto, Katharina A; Kahaly, George J

2012-09-01

Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.

Risk profile analysis and complications after surgery for autoimmune thyroid disease.

PubMed

Thomusch, O; Sekulla, C; Billmann, F; Seifert, G; Dralle, H; Lorenz, K

2018-05-01

Surgical approaches to autoimmune thyroid disease are currently hampered by concerns over postoperative complications. Risk profiles and incidences of postoperative complications have not been investigated systematically, and studies with sufficient power to show valid data have not been performed. A prospective multicentre European study was conducted between July 2010 and December 2012. Questionnaires were used to collect data prospectively on patients who had surgery for autoimmune thyroid disease and the findings were compared with those of patients undergoing surgery for multinodular goitre. Logistic regression analysis was used to evaluate risk factors for thyroid surgery-specific complications, transient and permanent recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism. Data were available for 22 011 patients, of whom 18 955 were eligible for analysis (2488 who had surgery for autoimmune thyroid disease and 16 467 for multinodular goitre). Surgery for multinodular goitre and that for autoimmune thyroid disease did not differ significantly with regard to general complications. With regard to thyroid surgery-specific complications, the rate of temporary and permanent vocal cord palsy ranged from 2·7 to 6·7 per cent (P = 0·623) and from 0·0 to 1·4 per cent (P = 0·600) respectively, whereas the range for temporary and permanent hypoparathyroidism was 12·9 to 20·0 per cent (P < 0·001) and 0·0 to 7·0 per cent (P < 0·001) respectively. In logistic regression analysis of transient and permanent vocal cord palsy, autoimmune thyroid disease was not an independent risk factor. Autoimmune thyroid disease, extent of thyroid resection, number of identified parathyroid glands and no autotransplantation were identified as independent risk factors for both transient and permanent hypoparathyroidism. Surgery for autoimmune thyroid disease is safe in comparison with surgery for multinodular goitre in terms of general complications and RLN palsy. To avoid the increased risk of postoperative hypoparathyroidism, special attention needs to be paid to the parathyroid glands. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

Autoimmune disease, familial clustering and thyroid carcinoma coexistent with autoimmune thyroiditis in children and adolescence: A cross-sectional study from the Czech Republic.

PubMed

Pomahacova, Renata; Zamboryova, Jana; Paterova, Petra; Fiklik, Karel; Cerna, Zdenka; Lad, Vaclav; Skalicka, Eva; Huml, Michal; Sykora, Josef

2018-06-07

The prevalence of autoimmune thyroiditis (AIT), as the most common autoimmune disease (AD) and papillary thyroid cancer (PTC) is steadily rising in children. The aim of this study was to determine the coexistence of other AD and thyroid carcinoma (TC) in AIT. The cross-sectional study conducted at a tertiary center comprised AIT children (< 19 years). Data on age/sex, thyroid function and ultrasound, autoantibodies, associated AD, familial occurence of AD and the occurence of TC for each child were collected. In total, 231 eligible patients (77% females) were included. The most common onset (66%) was during adolescence. At onset, hypothyroidism was detected in 59.3%; hashitoxicosis in 1.3%. The positivity of both autoantibodies was present in 60.6%, the negativity was in 3,5%. We confirmed a high frequency (44.6%) of AD with AIT predominance in parents and/or grandparents of patients and in siblings (7.4%). 15.2% had at least 1 comorbid AD, of which type 1 diabetes mellitus was the most common (8.5%). Over a period of 7 years TC was diagnosed in 16 patients (mean age 13.5 years) with predominance of PTC in 15 (94%) patients. AIT had concurrently 69% patients. 56% of patients had metastases (89% in AIT subjects). An invasive PTC was present in 44% (86% in AIT subjects). The prevalence rate of AD in AIT and first-degree relatives is high, and several new associations have been reported. Providers should be aware of comorbidities and TC in AIT as this would help in early diagnoses and timely interventions.

Autosomal-dominant non-autoimmune hyperthyroidism presenting with neuromuscular symptoms.

PubMed

Elgadi, Aziz; Arvidsson, C-G; Janson, Annika; Marcus, Claude; Costagliola, Sabine; Norgren, Svante

2005-08-01

Neuromuscular presentations are common in thyroid disease, although the mechanism is unclear. In the present study, we investigated the pathogenesis in a boy with autosomal-dominant hyperthyroidism presenting with neuromuscular symptoms. The TSHr gene was investigated by direct sequencing. Functional properties of the mutant TSHr were investigated during transient expression in COS-7 cells. Family members were investigated by clinical and biochemical examinations. Sequence analysis revealed a previously reported heterozygous missense mutation Glycine 431 for Serine in the first transmembrane segment, leading to an increased specific constitutive activity. Three additional affected family members carried the same mutation. There was no indication of autoimmune disorder. All symptoms disappeared upon treatment with thacapzol and L-thyroxine and subsequent subtotal thyroidectomy. The data imply that neuromuscular symptoms can be caused by excessive thyroid hormone levels rather than by autoimmunity.

Conversion of autoimmune hypothyroidism to hyperthyroidism.

PubMed

Furqan, Saira; Haque, Naeem-ul; Islam, Najmul

2014-08-03

Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

Is selenium supplementation in autoimmune thyroid diseases justified?

PubMed

Winther, Kristian H; Bonnema, Steen J; Hegedüs, Laszlo

2017-10-01

This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves' disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves' orbitopathy. The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves' disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.

In children with autoimmune thyroiditis CTLA4 and FCRL3 genes--but not PTPN22--are overexpressed when compared to adults.

PubMed

Wojciechowska-Durczynska, Katarzyna; Krawczyk-Rusiecka, Kinga; Zygmunt, Arkadiusz; Stawerska, Renata; Lewinski, Andrzej

2016-01-01

Numerous genetic studies revealed several susceptibility genes of autoimmune thyroid diseases (AITD), including CTLA4, PTPN22 and FCRL3. These immune-modulating genes are involved in genetic background of AITD among children and adult patients. However, possible age-related differences in overexpression of these genes remain unclear. The goal of this single centre cohort study was evaluation of expression levels of three (3) genes CTLA4, PTPN22 and FCRL3 in adult patients and children with autoimmune thyroiditis. A total of 47 patients--24 adults (mean age--47.7 years) and 23 children (mean age--12.4 years) with autoimmune thyroiditis were assessed for the level of expression of CTLA4, PTPN22 and FCRL3 genes, utilizing ABI PRISM' 7500 Sequence Detection System (Applied Biosystem, Foster City, CA, USA). The overexpression of PTPN22 (mean RQ = 2.988) and FCRL3 (mean RQ = 2.544) genes were confirmed in adult patients with autoimmune thyroiditis, at the same time the expression level of CTLA4 gene was significantly decreased (mean RQ = 0.899) (p < 0.05). Similar discrepancies were not observed in children with autoimmune thyroiditis in whom overexpression of all three genes--CTLA4, PTPN22 and FCRL3--was observed. Differences in CTLA4 and FCRL3 genes expression levels in patients with autoimmune thyroiditis were found depending on the age, with increased expression levels of CTLA4 (mean RQ = 3.45 1) and FCRL3 (mean RQ = 7.410) in children when compared to adults (p < 0.05) (Mann-Whitney's U-test). There were moderate negative linear correlations between two genes in question (CTLA4 and FCRL3) expression level and patients' age [correlation coefficient (r) = -0.529 (p < 0.0002) and -0.423 (p < 0.0032), respectively; Spearman's rank correlation test]. Our results are consistent with the hypothesis that there are few age-dependent genetic differences as regards autoimmune thyroiditis in adults and children. Accordingly, CTLA4 and FCRL3 genes overexpression may play an important role in children suffering from autoimmune thyroiditis.

Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

PubMed Central

Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

2012-01-01

Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

[100 years of Hashimoto thyroiditis, still an intriguing disease].

PubMed

Baretić, Maja

2011-12-01

In 1912 Japanese physician Hashimoto Hakaru described 4 patients with chronic thyroid disease. The histopathology findings exactly 100 years ago described lymphocyte infiltration, fibrosis, parenchymal atrophy and eosinophilic changes of some acinar cells. Those findings are typical for the autoimmune thyroid disease named by the author Hashimoto thyroiditis or lymphocytic thyroiditis. Hashimoto thyroiditis: The pathophysiology of thyroid autoimmunity during the past decades was described in details. Many thyroid antigens were identified (thyroid - stimulating hormone or TSH, thyroglobulin, thyreoperoxidase) and antibodies are directed towards them. Thyreocyte is also able to function as antigen presenting cell. It presents antigen on its surface and expresses MHC class II and class I molecules. Etiology of autoimmune thyroiditis combines genetic and environmental factors. Genetic factors dominate, and influence with about 80% on the occurrence of immunity. Some HLA genes (HLA-DR3, HLA-DR4, HLA-DR5 and HLA-DQA) and some non-HLA genes (cytotoxic T-lymphocyte antigen 4 -CTLA-4, CD40 gene, gene for protein tyrosine phosphatase 22 -PTPN22, thyroglobulin and TSH gene) are involved. 20% of etiology is attributed to environmental factors (smoking, iodine intake, selenium deficiency, pollution, infectious conditions, physical and emotional stress) and physiological states (puberty, rapid growth, pregnancy, menopause, aging, female gender). Although Hashimoto thyroiditis is known for many years, it is still sometimes presented with surprisingly diverse clinical entities and frequently astonishes many physicians. A case of a female patient with long-standing hypothesis (fine needle aspiration showed lymphocytic infiltration, thyreoperoxidase antibodies were positive) is presented. During the postpartum period, complicated with septic endometritis a new onset of hyperthyreosis appeared. The etiology of hyperthyroidism was unclear, with three possible explanations. The first one was that residual placental mass could cause prolonged exposure to beta- HCG. Beta- HCG causes hyperthyroidism mimicking action of TSH. The second explanation was that sepsis changes the nature of antibodies directed to the TSH receptor - thyrotrophin binding inhibitory antibodies become thyroid stimulating antibodies. The last explanation pointed to the pregnancy as a trigger itself that influenced on the immune events. Hyperthyreosis was followed by hypothyreosis and substitution with previous dosage of levothyroxine was continued. The answer of the sudden hyperthyreosis was given in subsequent pregnancy that happened 2,5 years later. The following one was free of complications, but postpartum hyperthyroidism occurred again. Further course of disease suited to lymphocytic thyroiditis with hypothyroidism, and she is substituted with levothyroxine until now. During normal pregnancy it is expected to have decreased ratio of CD4+/CD8+ lymphocyte subpopulation. Studies showed that women who developed postpartum thyroiditis had a higher ratio of CD4+/CD8+ and they were generally anti-TPO positive. It is considered that the lack of the expected suppression of immune function during pregnancy leads to postpartum thyroiditis. In this case Hashimoto thyroiditis showed two different faces: it was presented with long term hypothyroidism, but in postpartum period it converted to hyperthyroidism - a typical picture of postpartum thyroiditis. Pregnancy as a trigger can reveal till then unrecognized autoimmune disorder, or modify its course from hypothyroidism to hyperthyroidism. Hashimoto disease even 100 years after the discovery may surprise with one of its many faces.

Correlation between thyroidal and peripheral blood total T cells, CD8+ T cells, and CD8+ T- regulatory cells and T-cell reactivity to calsequestrin and collagen XIII in patients with Graves' ophthalmopathy.

PubMed

Al-Ansari, Farah; Lahooti, Hooshang; Stokes, Leanne; Edirimanne, Senarath; Wall, Jack

2018-05-22

Purpose/aim of the study: Graves' ophthalmopathy (GO) is closely related to the thyroid autoimmune disorder Graves' disease. Previous studies have suggested roles for thyroidal CD8 +  T cells and autoimmunity against calsequestrin-1 (CASQ)-1 in the link between thyroidal and orbital autoimmune reactions in GO. A role for autoimmunity against CollXIII has also been suggested. In this study, we aimed to investigate correlations between some thyroidal and peripheral blood T-cell subsets and thyroidal T-cell reactivity against CASQ1 and CollXIII in patients with GO. Fresh thyroid tissues were processed by enzyme digestion and density gradient to isolate mononuclear cells (MNCs). Peripheral blood MNCs were also isolated using density gradient. Flow-cytometric analysis was used to identify the various T-cell subsets. T -cell reactivity to CASQ1 and CollXIII was measured by a 5-day culture of the MNCs and BrdU uptake method. We found a positive correlation between thyroidal CD8 +  T cells and CD8 +  T-regulatory (T-reg) cells in patients with GO. Thyroidal T cells from two out of the three patients with GO tested (66.7%) showed a positive response to CASQ1, while thyroidal T cells from none of the six Graves' Disease patients without ophthalmopathy (GD) tested showed a positive response to this antigen. Thyroidal T cells from these patient groups however, showed no significant differences in their response to CollXIII. Our observations provide further evidence for a possible role of thyroidal CD8 +  T cells, CD8 +  T-reg cells and the autoantigen CASQ1 in the link between thyroidal and orbital autoimmune reactions of GO.

Oxidative Stress and Immune System in Vitiligo and Thyroid Diseases

PubMed Central

Colucci, Roberta; Dragoni, Federica

2015-01-01

Vitiligo is an acquired dermatological disease frequently associated with autoimmune thyroid disorders. Several theories have been proposed so far to unravel the complex vitiligo pathogenesis. Currently, the autocytotoxic and the autoimmune theories are the most accredited hypothesis, since they are sustained by several important clinical and experimental evidences. A growing body of evidences shows that autoimmunity and oxidative stress strictly interact to finally determine melanocyte loss. In this scenario, associated thyroid autoimmunity might play an active and important role in triggering and maintaining the depigmentation process of vitiligo. PMID:25838868

Enhanced Autoimmunity Associated with Induction of Tumor Immunity in Thyroiditis-Susceptible Mice

PubMed Central

Kari, Suresh; Flynn, Jeffrey C.; Zulfiqar, Muhammad; Snower, Daniel P.; Elliott, Bruce E.

2013-01-01

Background: Immunotherapeutic modalities to bolster tumor immunity by targeting specific sites of the immune network often result in immune dysregulation with adverse autoimmune sequelae. To understand the relative risk for opportunistic autoimmune disorders, we studied established breast cancer models in mice resistant to experimental autoimmune thyroiditis (EAT). EAT is a murine model of Hashimoto's thyroiditis, an autoimmune syndrome with established MHC class II control of susceptibility. The highly prevalent Hashimoto's thyroiditis is a prominent autoimmune sequela in immunotherapy, and its relative ease of diagnosis and treatment could serve as an early indicator of immune dysfunction. Here, we examined EAT-susceptible mice as a combined model for induction of tumor immunity and EAT under the umbrella of disrupted regulatory T cell (Treg) function. Methods: Tumor immunity was evaluated in female CBA/J mice after depleting Tregs by intravenous administration of CD25 monoclonal antibody and/or immunizing with irradiated mammary adenocarcinoma cell line A22E-j before challenge; the role of T cell subsets was determined by injecting CD4 and/or CD8 antibodies after tumor immunity induction. Tumor growth was monitored 3×/week by palpation. Subsequent EAT was induced by mouse thyroglobulin (mTg) injections (4 daily doses/week over 4 weeks). For some experiments, EAT was induced before establishing tumor immunity by injecting mTg+interleukin-1, 7 days apart. EAT was evaluated by mTg antibodies and thyroid infiltration. Results: Strong resistance to tumor challenge after Treg depletion and immunization with irradiated tumor cells required participation of both CD4+ and CD8+ T cells. This immunity was not altered by induction of mild thyroiditis with our protocol of Treg depletion and adjuvant-free, soluble mTg injections. However, the increased incidence of mild thyroiditis can be directly related to Treg depletion needed to achieve strong tumor immunity. Moreover, when a subclinical, mild thyroiditis was induced with soluble mTg and low doses of interleukin-1, to simulate pre-existing autoimmunity in patients subjected to cancer immunotherapy, mononuclear infiltration into the thyroid was enhanced. Conclusions: Our current findings indicate that genetic predisposition to autoimmune disease could enhance autoimmunity during induction of tumor immunity in thyroiditis-susceptible mice. Thus, HLA genotyping of cancer patients should be part of any risk assessment. PMID:23777580

A case report of neonatal thyrotoxicosis due to maternal autoimmune hyperthyroidism.

PubMed

Markham, Lori A; Stevens, Debra L

2003-12-01

A case of neonatal thyrotoxicosis secondary to maternal autoimmune hyperthyroidism is reported in an infant born at 34 weeks gestation who presented with tachycardia, jitteriness, diarrhea, and a small goiter. Propranolol and oxygen were used to treat high-output cardiac failure and transient persistent pulmonary hypertension. The infant's response to propylthiouracil therapy, gradual resolution of cardiac and systemic symptoms, and normaliziation of thyroid studies are described. Thyroid physiology and function and the special considerations in a premature infant are reviewed. An overview of maternal autoimmune hyperthyroidism and the implications for the developing fetus and neonate are presented. The risk factors for, and clinical presentation of, hyperthyroidism are outlined and treatment strategies highlighted. The nursing care of infants with hyperthyroidism is carefully described with an emphasis on the surveillance for and management of multisystem manifestations.

[Thyroiditis].

PubMed

Buffet, Camille; Groussin, Lionel

2013-02-01

The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

Necrobiosis lipoidica associated with Hashimoto's thyroiditis and positive detection of ANA and ASMA autoantibodies.

PubMed

Borgia, Francesco; Russo, Giuseppina T; Villari, Provvidenza; Guarneri, Fabrizio; Cucinotta, Domenico; Cannavò, Serafinella P

2015-07-01

Necrobiosis lipoidica (NL) is a rare idiopathic cutaneous condition exceptionally associated with autoimmune thyroiditis. We describe the first case of NL, Hashimoto's thyroiditis and positive detection of autoantibodies. Appropriate screening for NL in patients with autoimmune thyroiditis may clarify its real incidence and the existence of a common pathogenetic pathway.

Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

PubMed

Hogendorf, Anna; Pietrzak, Iwona; Antosik, Karolina; Borowiec, Maciej; Młynarski, Wojciech

2016-01-01

We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes. © Polish Society for Pediatric Endocrinology and Diabetology.

Environmental Issues in Thyroid Diseases.

PubMed

Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro; Benvenga, Salvatore

2017-01-01

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves' disease and Graves' ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction.

Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

NASA Astrophysics Data System (ADS)

Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

1985-04-01

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

Myxedema Coma due to Hashimoto Thyroiditis: A Rare but Real Presentation of Failure to Thrive in Infancy.

PubMed

Heksch, Ryan A; Henry, Rohan K

2018-05-04

Hashimoto thyroiditis (HT) is uncommon in infancy, and myxedema coma (MC) is even less common. While prior reports have documented these entities separately, to our knowledge, MC in combination with HT has not been reported before in this age group. A 10-month-old female presented with ptosis, lethargy, dysphagia, and failure to thrive (FTT). She developed hypotension, bradycardia, hypothermia, and apnea requiring intubation. Initial thyroid-stimulating hormone was 422 μIU/mL, and free thyroxine was < 0.5 ng/dL, despite the presence of a normal thyroid newborn screen (NBS). Of note, sepsis workup was unremarkable. With the diagnosis of MC, treatment with intravenous levothyroxine was initiated, although after hydrocortisone administration to avert the possibility of an adrenal crisis, despite a random cortisol of 16.4 μg/dL. Based on positive thyroid antibodies suggesting HT, autoimmune workup later revealed positive acetylcholinesterase antibodies consistent with a diagnosis of ocular myasthenia gravis. MC may be a cause of altered mental status in infancy and may simultaneously be associated with FTT on presentation. With the presence of a normal thyroid NBS, autoimmunity should be entertained as the etiology of profound hypothyroidism, as positive thyroid antibodies may prompt an exploration for coexisting diseases which may explain other presenting features. © 2018 S. Karger AG, Basel.

A Case of a TSH-secreting Pituitary Adenoma Associated with Evans' Syndrome.

PubMed

Yasuda, Atsushi; Seki, Toshiro; Oki, Masayuki; Takagi, Atsushi; Inomoto, Chie; Nakamura, Naoya; Atsumi, Hideki; Baba, Tanefumi; Matsumae, Mitsunori; Sasaki, Noriko; Suzuki, Yasuo; Fukagawa, Masafumi

2015-06-20

We present a case of a TSH-secreting pituitary adenoma (TSHoma) associated with Evans' syndrome. A 30-year-old woman was referred to our hospital due to purpura and ecchymoses on her limb and body and epistaxis. Evans' syndrome was diagnosed based on idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She had a history of malocclusion and thyroid gland enlargement 4 years prior to admission. Endocrinological tests and magnetic resonance imaging also revealed that this patient had hyperthyroidism due to the TSHoma and that this adenoma concomitantly secreted GH. Recently, several cases of Evans' syndrome were associated with hyperthyroidism caused by autoimmune thyroid disease, such as Graves' disease, suggesting that these 2 conditions may have a common immunological basis. To the best of our knowledge, there is no case report of Evans' syndrome associated with hyperthyroidism due to TSHoma. Our report suggests that the excess of thyroid hormone itself promotes autoimmunity in Evans' syndrome. Thus, early treatment for hyperthyroidism is necessary in TSHomas because of the possibility that thyroid hormone normalization may prevent the development of Evans' syndrome.

Histopathologic study of the so called 'palpation thyroiditis'.

PubMed Central

Hwang, T. S.; Park, S. H.

1988-01-01

We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis. PMID:3079564

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

PubMed

Imaizumi, Misa; Ohishi, Waka; Nakashima, Eiji; Sera, Nobuko; Neriishi, Kazuo; Yamada, Michiko; Tatsukawa, Yoshimi; Takahashi, Ikuno; Fujiwara, Saeko; Sugino, Keizo; Ando, Takao; Usa, Toshiro; Kawakami, Atsushi; Akahoshi, Masazumi; Hida, Ayumi

2017-07-01

The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study. Copyright © 2017 Endocrine Society

Evolution, immunity and the emergence of brain superautoantigens

PubMed Central

Nataf, Serge

2017-01-01

While some autoimmune disorders remain extremely rare, others largely predominate the epidemiology of human autoimmunity. Notably, these include psoriasis, diabetes, vitiligo, thyroiditis, rheumatoid arthritis and multiple sclerosis. Thus, despite the quasi-infinite number of "self" antigens that could theoretically trigger autoimmune responses, only a limited set of antigens, referred here as superautoantigens, induce pathogenic adaptive responses. Several lines of evidence reviewed in this paper indicate that, irrespective of the targeted organ (e.g. thyroid, pancreas, joints, brain or skin), a significant proportion of superautoantigens are highly expressed in the synaptic compartment of the central nervous system (CNS). Such an observation applies notably for GAD65, AchR, ribonucleoproteins, heat shock proteins, collagen IV, laminin, tyrosine hydroxylase and the acetylcholinesterase domain of thyroglobulin. It is also argued that cognitive alterations have been described in a number of autoimmune disorders, including psoriasis, rheumatoid arthritis, lupus, Crohn's disease and autoimmune thyroiditis. Finally, the present paper points out that a great majority of the "incidental" autoimmune conditions notably triggered by neoplasms, vaccinations or microbial infections are targeting the synaptic or myelin compartments. On this basis, the concept of an immunological homunculus, proposed by Irun Cohen more than 25 years ago, is extended here in a model where physiological autoimmunity against brain superautoantigens confers both: i) a crucial evolutionary-determined advantage via cognition-promoting autoimmunity; and ii) a major evolutionary-determined vulnerability, leading to the emergence of autoimmune disorders in Homo sapiens. Moreover, in this theoretical framework, the so called co-development/co-evolution model, both the development (at the scale of an individual) and evolution (at the scale of species) of the antibody and T-cell repertoires are coupled to those of the neural repertoires (i.e. the distinct neuronal populations and synaptic circuits supporting cognitive and sensorimotor functions). Clinical implications and future experimental insights are also presented and discussed. PMID:28529699

Glycyrrhizin, a Direct HMGB1 Antagonist, Ameliorates Inflammatory Infiltration in a Model of Autoimmune Thyroiditis via Inhibition of TLR2-HMGB1 Signaling.

PubMed

Li, Chenyan; Peng, Shiqiao; Liu, Xin; Han, Cheng; Wang, Xinyi; Jin, Ting; Liu, Shanshan; Wang, Weiwei; Xie, Xiaochen; He, Xue; Zhang, Hanyi; Shan, Ling; Fan, Chenling; Shan, Zhongyan; Teng, Weiping

2017-05-01

High mobility group box-1 (HMGB1), a non-histone protein, plays an important role in autoimmune diseases. However, the significance of HMGB1 in the pathogenesis of autoimmune thyroiditis has not been reported. The purpose of this study was to explore whether HMGB1 participates in the pathogenesis of autoimmune thyroiditis, and whether glycyrrhizin (GL), a direct inhibitor of HMGB1, attenuates the severity of thyroid inflammatory infiltration in a murine model of autoimmune thyroiditis. A total of 80 male NOD.H-2 h4 mice were randomly divided into a control or iodine supplement (NaI) group at four weeks of age, and the control group was fed with regular water, whereas the NaI group was supplied with 0.005% sodium iodine water. Another 24 male NOD.H-2 h4 mice were also randomized into three groups (eight mice per group) as follows: control, NaI, and GL treatment after iodine supplementation (NaI + GL). The NOD.H-2 h4 mice were fed with 0.005% sodium iodide water for eight weeks to enhance autoimmune thyroiditis. After iodine treatment, the mice received intraperitoneal injections of GL for four weeks. The severity of lymphocytic infiltration in the thyroid gland was measured by histopathological studies. The serum levels of HMGB1, tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, and thyroglobulin antibody titers were measured using an enzyme-linked immunosorbent assay. HMGB1 expression was measured by immunohistochemical staining and real-time polymerase chain reaction. TLR2, HMGB1, MyD88, and nuclear transcription factor κB were measured by Western blot. The mRNA expression of HMGB1 was significantly higher at 8 and 16 weeks in the NaI group than it was in the control group. Serum levels of thyroglobulin antibodies, HMGB1, tumor necrosis factor alpha, IL-6, and IL-1β were significantly increased in the NaI group, but they were dramatically attenuated with GL injection. The prevalence of thyroiditis and the infiltration of lymphocytes were significantly decreased in the NaI + GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and nuclear transcription factor κB in the thyroid gland and attenuated the severity of thyroiditis. HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. GL effectively attenuated thyroiditis in the iodine-induced NOD.H-2 h4 mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.

[Post-partum thyroiditis].

PubMed

Neves, Celestino; Alves, Marta; Delgado, Luís; Medina, J Luís

2009-01-01

In the post-partum period the immune alterations are associated with the multiple autoimmune diseases relapse. After birth, immune-tolerance variation slowly disappear, and is observed a return to a normal state - after an exacerbation period - of autoimmune reactivity, during which a great increase in T cells and autoantibodies is observed. In this period - 3 to 9 months after birth - the thyroid autoimmune disease relapses or reappears. The reactivation of the immune system in the post-partum period unchains an acute phase of celular destruction which characterizes the post-partum thyroiditis.

Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland?

PubMed

Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

2013-01-01

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD.

Radiation-related thyroid autoimmunity and dysfunction

PubMed Central

Nagayama, Yuji

2018-01-01

Abstract The thyroid gland is vulnerable not only to external radiation but also to internal radiation, because the thyroid cells can incorporate radioactive iodine when synthesizing thyroid hormones. Since radiation-induction of thyroid neoplasia, including thyroid cancer, is well recognized, the data on radiation-related thyroid autoimmunity and dysfunction are summarized and reviewed. High-dose irradiation, irrespective of being external or internal, is strongly associated with a risk of hypothyroidism (with the prevalence ranging from 2.4% to 31%) and of Graves’ hyperthyroidism (with the prevalence being up to 5%). It is easy to understand that high-dose irradiation induces hypothyroidism with some frequency, because high-dose irradiation destroys the thyroid gland. On the other hand, the basis for development of hyperthyroidism is mechanistically unclear, and it is merely speculative that autoantigens may be released from damaged thyroid glands and recognized by the immune system, leading to the development of anti-thyrotropin receptor antibodies and Graves’ hyperthyroidism in subjects who are immunologically predisposed to this ailment. In contrast, the data on moderate to low-dose irradiation on thyroid autoimmunity and dysfunction are inconsistent. Although it is difficult to draw a definitive conclusion, some data may suggest a transient effect of moderate- to low-dose irradiation on hypothyroidism and autoimmune thyroiditis, implying that the effect, if it exists, is reversible. Finally, no report has shown a statistically significant increase in the prevalence of moderate- to low-dose irradiation–induced Graves’ hyperthyroidism. PMID:29069397

Why is the thyroid so prone to autoimmune disease?

PubMed

Saranac, L; Zivanovic, S; Bjelakovic, B; Stamenkovic, H; Novak, M; Kamenov, B

2011-01-01

The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients. Copyright © 2011 S. Karger AG, Basel.

Celiac Disease and Thyroid Conditions

MedlinePlus

... whole body to slow down. This is called hypothyroidism. If your thyroid begins to over-produce hormones ... and Grave’s Disease are two common causes of hypothyroidism and hyperthyroidism (respectively). Both are autoimmune diseases: autoimmune ...

Hypothyrodism in male patients: a descriptive, observational and cross-sectional study in a series of 260 men.

PubMed

Iglesias, Pedro; Díez, Juan J

2008-10-01

Several aspects of thyroid dysfunction have not been fully characterized in large series of male patients. Our aim was to investigate the etiology and clinical features of hypothyroidism and assess the adequacy of replacement therapy in men attending an endocrinology clinic. We studied a group of 260 men (mean (+/-standard deviation) age 58.3 +/- 16.1 years) periodically seen because of thyroid hypofunction. We evaluated the etiology of hypothyroidism, presence or absence of goiter, time of evolution from diagnosis, current thyroid autoimmunity and thyroid functional status, and adequacy of disease control. Overt hypothyroidism was found in 182 (70.0%) and subclinical hypothyroidism in 78 (30.0%) patients. Autoimmune thyroiditis was the most frequent etiology (n = 107, 41.2%). Of these, 96 (89.7%) showed no goiter. Thyroid peroxidase antibodies were measured in 238 patients, being positive in 129 (54.2%) and negative in 109 (45.8%) patients. After excluding patients with thyroid carcinoma and those with recently diagnosed hypothyroidism, we found an adequate control of thyroid function, ie, normal thyrotropin and free thyroxine levels, in 95 patients (64.2%). Adequacy of treatment did not show any relationship with age, age at diagnosis, etiology, and autoimmune status. However, adequacy was significantly related to the degree of thyroid hypofunction (P < 0.001) and to the duration of disease (P < 0.01). We conclude that autoimmune thyroiditis, mainly the nongoitrous form, and postoperative hypothyroidism are the foremost causes of thyroid hypofunction in male patients. Adequacy of replacement treatment seems to be mainly related to the degree of thyroid hypofunction and the time from starting therapy.

Thyroiditis

MedlinePlus

... 12-18 months, 20% possibility of permanent hypothyroidism. Post partum thyroiditis Anti-thyroid antibodies, autoimmune disease Thyrotoxicosis followed by hypothyroidism. Thyroid function tests, thyroid antibody tests, radioactive iodine uptake (contraindicated if ...

Fetal microchimeric cells in autoimmune thyroid diseases

PubMed Central

Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

2013-01-01

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

Low levels of circulating platelet factor 4 (PF4, CXCL4) in subclinically hypothyroid autoimmune thyroiditis.

PubMed

Görar, S; Ademoğlu, E; Çarlıoğlu, A; Alioğlu, B; Bekdemir, H; Sağlam, B; Candan, Z; Üçler, R; Culha, C; Aral, Y

2016-02-01

Chemokines play an important role in the pathogenesis of autoimmune thyroid diseases. Platelet factor 4 (PF4, CXCL4) released from activated platelets is a chemokine. However, its clinical importance in autoimmune thyroiditis remains unknown. This study is intended to determine circulating levels of PF4 levels in patients with autoimmune thyroiditis (AIT). Circulating levels of PF4 were measured in 34 consecutive patients with newly diagnosed AIT and 18 euthyroid controls. Among AIT group, 16 patients were euthyroid and 18 had subclinic hypothyroidism. Controls and individuals with AIT were similar in terms of age. Serum levels of PF4 were comparable in patients with AIT and in controls. Among patients with AIT, PF4 was significantly lower in those with subclinical hypothyroidism than in euthyroid individuals (p = 0.001). In correlation analysis, PF4 was negatively correlated with TSH (r = -0.663, p = 0.000) and positively correlated with free T4 (r = 0.428, p = 0.012). There was not any significant correlation between PF4 and AbTPO, AbTg. The present study demonstrated for the first time that circulating PF4 levels are decreased in subclinically hypothyroid AIT. This result draws attention to the circulating PF4 levels in subclinically hypothyroid AIT and may shed light on further researches at this topic.

Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

PubMed

Ramos-Leví, Ana Maria; Marazuela, Mónica

2016-10-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs). Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Immunological Reactivity Using Monoclonal and Polyclonal Antibodies of Autoimmune Thyroid Target Sites with Dietary Proteins

PubMed Central

Herbert, Martha

2017-01-01

Many hypothyroid and autoimmune thyroid patients experience reactions with specific foods. Additionally, food interactions may play a role in a subset of individuals who have difficulty finding a suitable thyroid hormone dosage. Our study was designed to investigate the potential role of dietary protein immune reactivity with thyroid hormones and thyroid axis target sites. We identified immune reactivity between dietary proteins and target sites on the thyroid axis that includes thyroid hormones, thyroid receptors, enzymes, and transport proteins. We also measured immune reactivity of either target specific monoclonal or polyclonal antibodies for thyroid-stimulating hormone (TSH) receptor, 5′deiodinase, thyroid peroxidase, thyroglobulin, thyroxine-binding globulin, thyroxine, and triiodothyronine against 204 purified dietary proteins commonly consumed in cooked and raw forms. Dietary protein determinants included unmodified (raw) and modified (cooked and roasted) foods, herbs, spices, food gums, brewed beverages, and additives. There were no dietary protein immune reactions with TSH receptor, thyroid peroxidase, and thyroxine-binding globulin. However, specific antigen-antibody immune reactivity was identified with several purified food proteins with triiodothyronine, thyroxine, thyroglobulin, and 5′deiodinase. Laboratory analysis of immunological cross-reactivity between thyroid target sites and dietary proteins is the initial step necessary in determining whether dietary proteins may play a potential immunoreactive role in autoimmune thyroid disease. PMID:28894619

Subclinical Hypothyroidism: A Prospective Observational Study from Southern India.

PubMed

Sridhar, Mathrubootham; Mahadevan, Shriraam; Vishwanathan, Latha; Subbarayan, Anbezhil

2018-03-15

To assess the natural history and progression of subclinical hypothyroidism and to study factors which help predict evolution of subclinical hypothyroidism into overt hypothyroidism. Longitudinal study in 40 children (2-16 yrs) presenting with subclinical hypothyroidism in a tertiary care unit in Chennai, India. Patients showing evidence of overt hypothyroidism or thyroid stimulating hormone ≥15 mIU/mL during follow-up were started on thyroxine. Others were followed up with 3-monthly thyroid function tests up to one year. At the end of our study period 3 (7.5%) were overtly hypothyroid, 16 (40%) remained as subclinical hypothyroid, and 21 (52.5%) became euthyroid. Evidence of auto- immunity at baseline was a significant (P<0.05) risk factor for progression to overt hypothyroidism. Subclinical hypothyroidism in children, with thyroid stimulating hormone upto 15 mIU/L and irrespective of thyroid autoimmunity, needs only periodic clinical and biochemical follow up. Thyroid autoimmunity may point to an increased probability of progression to overt hypothyroidism.

Complicating autoimmune diseases in myasthenia gravis: a review

PubMed Central

Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

2015-01-01

Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

Importance of Delphian Lymph Node Evaluation in Autoimmune Thyroiditis: Fact or Fiction?

PubMed Central

Ormeci, Tugrul; Çolakoğulları, Mukaddes; Orhan, İsrafil

2016-01-01

Summary Background Our main objective was to evaluate the association between autoimmune thyroiditis and the Delphian lymph node during different stages of thyroiditis. Material/Methods The relationships between the ultrasonography (US) results of thyroiditis and characteristics of the Delphian lymph node in different stages of AT were evaluated. Thyroid hormone and antibody levels were assessed. A total of 126 patients were divided into four groups according to the thyroid US findings: Group 1: control cases; Group 2: indeterminate cases; Group 3: established thyroiditis cases; Group 4: advanced-late stage thyroiditis cases. Indeterminate cases attended a 1-year follow-up, and the cases with a sonographic finding matching thyroiditis formed Group 2. Results The rate of Delphian lymph node presence in Group 4 was significantly higher than in Groups 1 and 2 (p<0.01). In addition, its presence was significantly higher in Group 3 than in Group 1 (p<0.05). Although there was a difference in Delphian lymph node presence between Groups 2 and 3, it was not significant (p=0.052), nor was there a significant difference between Groups 1 and 2 (p>0.05). Both the long and short axis measurements were significantly higher in Groups 2, 3, and 4 compared to those in the control group. However, the same increase was not observed in the long/short axis ratio. Conclusions Both the presence and dimensions of the Delphian lymph node were highly correlated with the progress of autoimmune thyroiditis. Evaluating the Delphian lymph nodes might prevent missing a diagnosis of autoimmune thyroiditis. PMID:26985243

[Severe hyperlipidemia, secondary to hypothyroidism due to atrophic thyroiditis in a girl].

PubMed

Pacín, Mirta

2009-02-01

We present a 5 years 8 months old girl with severe hyperlipidemia (high total cholesterol, and low density lipoprotein values, and also, ectopic fat pericardial deposit). She was treated with diet and cholestyramine, without diagnosis of her disease etiology. Growth detention, weight loss, retarded bone age and clinical signs of hypometabolism were recorded. Thyroid profile confirms hypothyroidism diagnosis. Based on positive anti-thyroid antibodies and clearly reduced thyroid volume, a diagnosis of autoimmune atrophic thyroiditis was made, a very unusual pathology in early infancy. Linear growth was affected by late diagnosis.

Down syndrome, insulin-dependent diabetes mellitus and hyperthyroidism: a rare association

PubMed Central

Marques, Inês; Silva, Ana; Castro, Sofia; Lopes, Lurdes

2015-01-01

The association between Down syndrome (DS) and autoimmune endocrinopathies is well established. These disorders become increasingly frequent as children grow older and the onset of one often predisposes to the development of others. However, there are few cases in the literature reporting the simultaneous onset of type 1 diabetes mellitus and hyperthyroidism in children with DS. We describe a case of an 8-year-old girl with DS who presented at the emergency department with hyperglycaemia and ketosis as a primary manifestation of type 1 diabetes mellitus. During the initial investigation, hyperthyroidism was detected, with thyroid-stimulating hormone<0.01 µUI/mL, positive antithyroid antibodies and an increase in thyroid gland on ultrasound. The authors present this case to underline the usefulness of monitoring thyroid function at the diagnosis of diabetes, even without apparent clinical manifestations, and to alert for the possibility of autoimmune endocrine dysfunction in children with DS. PMID:26123455

[Sub-acute thyroiditis in a patient on immunosuppressive treatment].

PubMed

D'Amico, Giovanna; Di Crescenzo, Vincenzo; Caleo, Alessia; Garzi, Alfredo; Vitale, Mario

2013-01-01

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis.

PubMed

Maleki, N; Tavosi, Z

2015-02-01

To evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes and to investigate the frequency of postpartum thyroiditis in women with gestational diabetes. A total of 350 women with gestational diabetes and 350 healthy pregnant women were enrolled in the study. We studied the thyroid hormone profiles of the women in each group during pregnancy (at 24-28 weeks' gestation) and after delivery (at 6 weeks, 3, 6 and 9 months, and 1 year postpartum). A total of 342 women with gestational diabetes and 313 healthy pregnant women completed the follow-up during pregnancy and 1 year after delivery. Of the women with gestational diabetes, 16.6% had thyroid dysfunction, while of the healthy pregnant women, 6.1% had thyroid dysfunction. The prevalence of postpartum thyroiditis was higher in the women with a history of gestational diabetes (19.6%) than in the healthy pregnant women (10.2%), and this difference was statistically significant. According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes than in healthy women. We recommend that all women with gestational diabetes and women who have previous thyroid dysfunction should be screened for thyroid hormonal abnormalities during pregnancy and for 1 year after pregnancy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis.

PubMed

Winther, Kristian Hillert; Wichman, Johanna Eva Märta; Bonnema, Steen Joop; Hegedüs, Laszlo

2017-02-01

By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (≥18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta-analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well-powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis.

CCR5-Δ32 gene polymorphism is related to celiac disease and autoimmune thyroiditis coincidence in patients with type 1 diabetes.

PubMed

Słomiński, Bartosz; Ławrynowicz, Urszula; Myśliwska, Jolanta; Ryba-Stanisławowska, Monika; Skrzypkowska, Maria; Myśliwiec, Małgorzata; Brandt, Agnieszka

2017-03-01

The aim of the study was to assess the relationship between CCR5-Δ32 polymorphism and the coincidence of celiac and autoimmune thyroid diseases with type 1 diabetes mellitus (T1D) in children. 420 children with T1D aged 15.5±3.0years and 350 healthy controls were studied. Characterization of CCR5-Δ32 genotypes (rs333) was analyzed by polymerase chain reaction (PCR). The allele frequency was significantly different in diabetic children as compared to the healthy controls (p<0.0001). We found negative association between T1D and Δ32 allele (OR=0.383; 95% CI=0.268-0.549). Besides, we observed alterations in the frequencies of CCR5-Δ32 genotypes due to celiac and autoimmune thyroid diseases. The risk of celiac disease for patient carriers of the 32-bp deletion was more than threefold higher than for noncarriers (OR=3.490; 95% CI=1.357-8.859; p=0.009). Similar results were obtained in the case of autoimmune thyroiditis. The risk of autoimmune thyroiditis for patient carriers of the 32-bp deletion was also more than threefold higher than for noncarriers (OR=3.466; 95% CI=1.754-6.849; p=0.0004). The findings of our studies suggest that the CCR5-Δ32 polymorphism is associated with type 1 diabetes mellitus and the Δ32 allele increases the risk of celiac disease and autoimmune thyroid disorders in patients with T1D. Copyright © 2016 Elsevier Inc. All rights reserved.

Autoimmune thyroiditis in children and adolescents with type 1 diabetes mellitus is associated with elevated IgG4 but not with low vitamin D.

PubMed

Demir, Korcan; Keskin, Mehmet; Kör, Yilmaz; Karaoğlan, Murat; Bülbül, Özlem Gümüştekin

2014-01-01

To assess levels of vitamin D and of immunoglobulin G subclasses in children and adolescents with type 1 Diabetes Mellitus with or without autoimmune thyroiditis. Among 213 patients with type 1 diabetes, the cases with thyroid-specific autoantibodies formed Group 1 [n=19, M/F: 7/12, median age 13 years (10.1-14.7)]. Nineteen age-, gender-, and diabetes duration-matched cases with type 1 diabetes without any other systemic disease were designated as controls [Group 2, M/F: 7/12, median age 12.9 years (10.5-14.9)]. Levels of thyroid hormones, vitamin D, total IgG and IgG subclasses, as well as IgG subclasses/total IgG ratios were similar between the groups. Five cases (26%) in Group 1 had IgG4 levels > + 2 SDS, whereas there were no such cases in Group 2 (p=0.046). These five patients had similar clinical features but higher median IgG4 levels and IgG4/Total IgG ratios compared to the subjects with IgG4 levels < + 2 SDS in Group 1 and Group 2. There was no difference of vitamin D levels between the groups. Only a small percentage of patients with type 1 diabetes also having autoimmune thyroiditis had elevated serum IgG4 levels, revealing the heterogeneity of autoimmune thyroiditis and existence of IgG4 thyroiditis in the pediatric age group. Total IgG, the other IgG subclasses, and vitamin D levels did not differ in patients with autoimmune thyroiditis and type 1 diabetes compared to those suffering only from type 1 diabetes.

Thyroid Disorders Associated with Alopecia Areata in Egyptian Patients

PubMed Central

Bakry, Ola A; Basha, Mohamed A; El Shafiee, Maather K; Shehata, Wafaa A

2014-01-01

Context: Alopecia areata (AA) is a common form of localized, non-scarring hair loss. The etiopathogenesis of the disease is still unclear, but the role of autoimmunity is strongly suggested. AA is commonly associated with various autoimmune disorders; the most frequent among them is autoimmune thyroid disorders. Aim: To determine whether AA is associated with thyroid autoimmunity or thyroid function abnormalities in Egyptian patients. Materials and Methods: Fifty subjects with AA (37 males and 13 females) without clinical evidence of thyroid disorders were selected from Dermatology Outpatient Clinic, Menoufiya University Hospital, Menoufiya Governorate, Egypt, during the period from June 2009 to February 2010. They were divided into 3 groups according to severity of AA. Fifty age and sex-matched healthy volunteers (35 males and 15 females) were selected as a control group. Every case and control were subjected to history taking, complete general and dermatological examination. Venous blood samples were taken from cases and controls after taking their consents for measurement of thyroid stimulating hormone (TSH), free T3, freeT4 and detection of Anti-thyroglobulin Antibody (Tg-Ab) and Anti-thyroid Peroxidase Antibody (TPO-Ab). Results: Subclinical hypothyroidism was detected in 16% of cases. There were statistically significant differences between cases and controls regarding levels of TSH, free T3 and free T4. There were significant differences between cases and controls regarding the presence of Tg-Ab and TPO-Ab. Conclusions: Every patient with AA should be screened for thyroid functions and presence of thyroid autoantibodies even in absence of clinical manifestations suggestive of thyroid affection. PMID:24470660

Generalised pruritus as a presentation of Grave's disease.

PubMed

Tan, Ce; Loh, Ky

2013-01-01

Pruritus is a lesser known symptom of hyperthyroidism, particularly in autoimmune thyroid disorders. This is a case report of a 27-year-old woman who presented with generalised pruritus at a primary care clinic. Incidental findings of tachycardia and a goiter led to the investigations of her thyroid status. The thyroid function test revealed elevated serum free T4 and suppressed thyroid stimulating hormone levels. The anti-thyroid antibodies were positive. She was diagnosed with Graves' disease and treated with carbimazole until her symptoms subsided. Graves' disease should be considered as an underlying cause for patients presenting with pruritus. A thorough history and complete physical examination are crucial in making an accurate diagnosis. Underlying causes must be determined before treating the symptoms.

Estimation of Salivary Parameters among Autoimmune Thyroiditis Patients.

PubMed

Syed, Yasmeen Amthul; Reddy, Bh Satheesh; Ramamurthy, T K; Rajendra, Kavitha; Nerella, Narendra Kumar; Krishnan, Meenakshi; Ramesh, M V; Mohammed, Rezwana Begum

2017-07-01

Saliva is a complex secretion that protects and lubricates the oral cavity. Various systemic diseases and their treatment alter the salivary gland function; one such disease is Autoimmune Thyroid Disease (AITD). AITD has been postulated to exert its hormonal influence on the salivary glands, leading to reduced salivary output. There's a paucity of literature, verifying the stated conjunction in human subjects. The aim was to investigate the salivary profile in AITD patients and its comparison with controls. Descriptive cross-sectional comparative study was conducted using convenience sampling method for screening the presence of thyroid disorders. Two groups comprising of 30 patients in each group diagnosed with autoimmune hypothyroiditis (n=30) and hyperthyroiditis (n=30) respectively and thirty healthy volunteers who were age and sex matched were included as controls. Saliva was collected and evaluated for Unstimulated Salivary Flow Rate (USSFR), pH and buffer capacity. ANOVA and Tukey post-hoc test was performed to find the statistical significance and for pairwise comparison. Statistically significant difference was observed between autoimmune hypothyroiditis, autoimmune hyperthyroiditis and control group with respect to USSFR (p<0.007), pH (p<0.001) and buffer capacity (p<0.001). On pairwise comparisons statistically significant difference was observed between autoimmune hypothyroiditis and autoimmune hyperthyroiditis with respect to controls. We conclude that significant involvement of salivary glands may occur in cases of AITD. Our study showed significant reduction of sialometric values in AITD patients when compared to controls. A strong clinical suspicion of thyroid diseases should be considered when there is chronic hyposalivation; hence thyroid profile must also be done, if the known causes have been excluded.

Molecular basis for the autoreactivity against thyroid stimulating hormone receptor.

PubMed

Kohn, L D; Kosugi, S; Ban, T; Saji, M; Ikuyama, S; Giuliani, C; Hidaka, A; Shimura, H; Akamizu, T; Tahara, K

1992-01-01

The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)

Hashimoto thyroiditis associated with ataxia telangiectasia.

PubMed

Patiroglu, Turkan; Gungor, Hatice Eke; Unal, Ekrem; Kurtoglu, Selim; Yikilmaz, Ali; Patiroglu, Tahir

2012-01-01

Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

PubMed Central

Fröhlich, Eleonore; Wahl, Richard

2017-01-01

Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

[Hypothyreodism. From the latent functional disorder up to coma].

PubMed

Hintze, G; Derwahl, M

2010-05-01

An autoimmune thyroiditis represents the main reason of hypothyroidism, defined as a lack of thyroid hormone. This autoimmune process results in destruction of functioning thyroid follicles. While subclinical or latent hypothyroidism is defined on the basis of laboratory values (an elevation of TSH with normal peripheral hormone levels), the typical signs and symptoms are associated with hypothyroidism. In about 80% of cases antibodies against thyroid peroxidase can be measured, but only in about 40-50% of cases antibodies against thyroglobulin are detectable. If hypothyrodism has been diagnosed, substitution with levothyroxine should be initiated, with the therapeutic goal to decrease TSH level to the lower normal range. In cases of subclinical hypothyroidism, levothyroxine medication should be started in patients with a high TSH value, positive antibodies and/or the typical ultrasound of autoimmune thyroiditis. However, substitution with levothyroxine in any case of elevated TSH values should be avoided.

Anti‑livin antibodies in Hashimoto thyroiditis.

PubMed

Baumann-Antczak, Aleksandra; Kosowicz, Jerzy; Zamysłowska, Hanna; Ruchała, Marek

2012-01-01

Livin belongs to the family of apoptosis inhibitors. High livin expression is observed in malignancies of the gastrointestinal tract, lungs, breast, and kidneys, but it is not present in differentiated adult tissues. In some malignant processes, anti‑livin antibodies are present. The aim of the study was to evaluate the prevalence of anti‑livin antibodies in Hashimoto thyroiditis, a disease characterized by rapid and widespread thyrocyte apoptosis. The study comprised 65 women with Hashimoto thyroiditis and the control group of 40 healthy women. In the majority of the patients, clinical manifestations of hypothyroidism were observed; all patients had high levels of serum antithyroid peroxidase antibodies. A solid‑phase radioimmunoassay in livin‑coated polyethylene tubes using 125I-labeled protein A was used to determine anti-livin antibodies. Significant amounts of anti-livin antibodies were reported in 18 patients (26.8%); 3 patients (4.6%) had borderline antibody levels; while in controls only 1 patient was positive (2.5%, P <0.0001). In Hashimoto thyroiditis, an autoimmune process is more general and involves numerous autoantibodies including an antibody against apoptosis inhibitor - livin. Anti‑livin antibodies cannot serve only as a marker of malignancy because they are also present in autoimmune processes.

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

PubMed

Guaraldi, F; La Selva, R; Samà, M T; D'Angelo, V; Gori, D; Fava, P; Fierro, M T; Savoia, P; Arvat, E

2018-05-01

Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Impact of positive thyroid autoimmunity on pregnant women with subclinical hypothyroidism.

PubMed

López-Tinoco, Cristina; Rodríguez-Mengual, Amparo; Lara-Barea, Almudena; Barcala, Julia; Larrán, Laura; Saez-Benito, Ana; Aguilar-Diosdado, Manuel

2018-03-01

The impact of subclinical hypothyroidism (SH) and thyroid autoimmunity on obstetric and perinatal complications continues to be a matter of interest and highly controversial. To assess the impact of SH and autoimmunity in early pregnancy on the obstetric and perinatal complications in our population. A retrospective cohort study in 435 women with SH (TSH ranging from 3.86 and 10 μIU/mL and normal FT4 values) in the first trimester of pregnancy. Epidemiological and clinical parameters were analyzed and were related to obstetric and perinatal complications based on the presence of autoimmunity (thyroid peroxidase antibodies [TPO] > 34 IU/mL). Mean age was 31.3 years (SD 5.2). Seventeen percent of patients had positive TPO antibodies. Presence of positive autoimmunity was associated to a family history of hypothyroidism (P=.04) and a higher chance of miscarriage (P=.009). In the multivariate analysis, positive TPO antibodies were associated to a 10.25-fold higher risk of miscarriage. No statistically significant associations were found with all other obstetric and perinatal complications. In our region, pregnant women with SH and thyroid autoimmunity had a higher risk of miscarriage but not of other obstetric and perinatal complications. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Childhood Weight Gain and Thyroid Autoimmunity at Age 60–64 Years: The 1946 British Birth Cohort Study

PubMed Central

Kuh, Diana; Pierce, Mary; Franklyn, Jayne A.

2013-01-01

Background: Complex bidirectional relationships have been described between body weight, thyroid function, and risk of thyroid disorders, including thyroid autoimmunity. We used a life-course approach to examine the potential association of childhood or adult body weight with the risk of thyroid autoimmunity and other thyroid disorders at age 60–64 years in a large population-based birth cohort study. Methods: In the UK Medical Research Council 1946 British Birth Cohort study, at age 60–64 years, 1277 women and 1185 men (78% of the target sample) responded to a postal questionnaire, which included questions on thyroid disease and thyroid medication. Circulating antithyroid peroxidase antibodies, free T4, and TSH concentrations were measured in 1057 women and 997 men at a subsequent clinic visit. Birth weight was recorded, and height and weight were measured at ages 2, 4, 6, 7, 11, 15 years and also repeatedly in adulthood. Results: At age 60–64 years, 10.9% of women (139 of 1277) and 2.3% of men (27 of 1185) reported they were taking T4, and 11.5% of women (122 of 1057) and 3.3% of men (33 of 997) had positive anti-TPO antibodies (>100 IU/mL), consistent with thyroid autoimmunity. Among women, both T4 use and positive anti-TPO antibodies at age 60–64 years were positively associated with childhood body weight, childhood overweight, and adult body mass index. Childhood weight gain between 0 and 14 years of age was positively associated with later T4 use (odds ratio 1.21, 95% confidence interval 1.03–1.42) and positive anti-TPO antibodies (1.21, 1.00–1.47). Women who were overweight or obese at age 14 years (127 of 972) had a higher risk of later positive anti-TPO antibodies (2.05, 1.12–3.76). In men and women without any thyroid disorders, serum free T4 concentrations were inversely associated with concurrent body mass index (P = .002). Conclusions: Childhood weight gain and childhood overweight conferred an increased susceptibility to later hypothyroidism and thyroid autoimmunity, particularly in women. PMID:23436917

[Atypical subacute thyroiditis in combination with Grave's disease:Diagnostic difficulties in a case report].

PubMed

Koutouridou, Emmanouela; Planck, Tereza; Uddman, Erik; Lantz, Mikael

2018-04-13

Subacute thyroiditis is a common inflammatory disorder of the thyroid gland, possibly of viral etiology, that typically presents with neck pain, fever and tenderness on palpation of the thyroid gland. Graves' disease is an autoimmune thyroid disorder caused by stimulation of the thyroid gland by thyrotropin receptor antibodies (TRAb). The development of Graves´ disease and subacute thyroiditis simultaneously is an uncommon condition and only a few cases have been reported. In this article we present a case of a 46-year old woman diagnosed with Graves´ disease who was started on thiamazole and weeks later developed high fever. Several differential diagnoses were considered such as infection, lymphoma and vasculitis due to thiamazole. Finally, the fine needle aspiration of the thyroid gland displayed histopathological features of subacute thyroiditis. Remarkably, our patient did not have neck pain or tenderness on palpation of the thyroid gland and overall the clinical presentation of subacute thyroiditis was atypical. Thus, subacute thyroiditis may be considered as a potential cause of fever of unknown origin.

Mathematical model describing the thyroids-pituitary axis with distributed time delays in hormone transportation

NASA Astrophysics Data System (ADS)

Neamţu, Mihaela; Stoian, Dana; Navolan, Dan Bogdan

2014-12-01

In the present paper we provide a mathematical model that describe the hypothalamus-pituitary-thyroid axis in autoimmune (Hashimoto's) thyroiditis. Since there is a spatial separation between thyroid and pituitary gland in the body, time is needed for transportation of thyrotropin and thyroxine between the glands. Thus, the distributed time delays are considered as both weak and Dirac kernels. The delayed model is analyzed regarding the stability and bifurcation behavior. The last part contains some numerical simulations to illustrate the effectiveness of our results and conclusions.

Efficacy of a food supplement in patients with hashimoto thyroiditis.

PubMed

Nordio, M; Basciani, S

2015-01-01

Thyroid inflammation has been commonly seen in recent decades, due to a series of factors and is considered as the most frequent thyroid illness. It is characterized by some distinctive traits, which include morphological and hormonal modifications, often in association with an elevated anti-thyroid autoantibody title. The aim of the therapy is to improve symptoms as fast as possible, treating inflammation and subsequent hypothyroidism, when present. Therefore, we evaluated the efficacy of a Food Supplement (FS) containing enzymes which is commonly used in various inflammatory processes and is able to modulate immune reactions during inflammation in a very rapid and efficacious way. An open, controlled study was then designed and 45 patients with Hashimoto thyroiditis were enrolled and divided into 3 groups (FS alone; thyroid hormones alone; FS plus thyroid hormones). Blood, morphological and subjective parameters were considered. The results obtained indicate that the FS used in our study is efficacious and safe when used alone and/or in combination with thyroid hormones in the treatment of autoimmune thyroiditis, as documented by the improvement of the majority of the parameters considered. The efficacy was considered faster than thyroid hormones alone as far as subjective symptomatology is considered. In conclusion, the use of the food supplement evaluated herein during inflammation may be considered an additional tool in clinicians’ hands, when facing patients with autoimmune thyroiditis, especially in presence of subjective symptomatology, in order to rapidly alleviate it.

Estimation of Salivary Parameters among Autoimmune Thyroiditis Patients

PubMed Central

Reddy, BH Satheesh; Ramamurthy, TK; Rajendra, Kavitha; Nerella, Narendra Kumar; Krishnan, Meenakshi; Ramesh, MV; Mohammed, Rezwana Begum

2017-01-01

Introduction Saliva is a complex secretion that protects and lubricates the oral cavity. Various systemic diseases and their treatment alter the salivary gland function; one such disease is Autoimmune Thyroid Disease (AITD). AITD has been postulated to exert its hormonal influence on the salivary glands, leading to reduced salivary output. There’s a paucity of literature, verifying the stated conjunction in human subjects. Aim The aim was to investigate the salivary profile in AITD patients and its comparison with controls. Materials and Methods Descriptive cross-sectional comparative study was conducted using convenience sampling method for screening the presence of thyroid disorders. Two groups comprising of 30 patients in each group diagnosed with autoimmune hypothyroiditis (n=30) and hyperthyroiditis (n=30) respectively and thirty healthy volunteers who were age and sex matched were included as controls. Saliva was collected and evaluated for Unstimulated Salivary Flow Rate (USSFR), pH and buffer capacity. ANOVA and Tukey post-hoc test was performed to find the statistical significance and for pairwise comparison. Results Statistically significant difference was observed between autoimmune hypothyroiditis, autoimmune hyperthyroiditis and control group with respect to USSFR (p<0.007), pH (p<0.001) and buffer capacity (p<0.001). On pairwise comparisons statistically significant difference was observed between autoimmune hypothyroiditis and autoimmune hyperthyroiditis with respect to controls. Conclusion We conclude that significant involvement of salivary glands may occur in cases of AITD. Our study showed significant reduction of sialometric values in AITD patients when compared to controls. A strong clinical suspicion of thyroid diseases should be considered when there is chronic hyposalivation; hence thyroid profile must also be done, if the known causes have been excluded. PMID:28893031

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

PubMed

Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

2015-09-01

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap.

PubMed

Marta, Guilherme Nader; de Campos, Fernando Peixoto Ferraz

2015-01-01

Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 10(9)/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave's disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave's disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy.

Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

PubMed Central

de Campos, Fernando Peixoto Ferraz

2015-01-01

Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave’s disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy. PMID:26484334

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase.

PubMed

Sharma, Rajni; Di Dalmazi, Giulia; Caturegli, Patrizio

2016-08-01

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2(h4) mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. NOD-H2(h4) mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. This study shows that CTLA-4 blockade exacerbates the iodine-accelerated form of thyroiditis typical of the NOD-H2(h4) mouse. The study could also have implications for cancer patients who develop thyroiditis as an immune-related adverse event after CTLA-4 blockade.

Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis.

PubMed

Zivancevic-Simonovic, Snezana; Mihaljevic, Olgica; Majstorovic, Ivana; Popovic, Suzana; Markovic, Slavica; Milosevic-Djordjevic, Olivera; Jovanovic, Zorica; Mijatovic-Teodorovic, Ljiljana; Mihajlovic, Dusan; Colic, Miodrag

2015-08-01

Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); Th9-interleukin 9 (IL-9); and Th17-interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for human Th1/Th2/Th9/Th17/Th22. We found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity.

Novel insights in ultrasound evaluation of thyroid gland in children with papillary thyroid carcinoma.

PubMed

Janus, Dominika; Wojcik, Malgorzata; Kalicka-Kasperczyk, Anna; Drabik, Grazyna; Wyrobek, Lukasz; Wedrychowicz, Anna; Starzyk, Jerzy B

2017-10-01

The coincidence of autoimmune thyroiditis (AIT) in patients with papillary thyroid carcinoma (PTC) is ranging between 10 and 58% in the general population. In the present study retrospective ultrasound, clinical and autoimmune assessment of 24 patients diagnosed with papillary thyroid carcinoma between 2000-2016 was performed. The coexistence of PTC and AIT was found in 50% of patients with PTC. Patients were divided into two groups. PTC AIT (+) group involved 12 children at the mean age 14.9 years (range 11-20 years, 9 girls) and PTC AIT (-) 12 children at the mean age 12.9 years (range 7-18 years, 5 girls). Papillary thyroid microcarcinoma (PTMC) was diagnosed in 6 patients (in 5 with AIT). US characteristics of PTC was heterogenous: hypoechogenic with/without increased vascularisation, normoechogenic with halo, with/without microcalcifications. In 70% PTC AIT (+) and in all PTC AIT (-) patients ultrasound analysis revealed that the thyroid tissue of the whole gland was normoechogenic. Local metastases in lymph nodes were found in 40% of PTMC AIT (+). Lack of increased vascularization and microcalcifications and presence of``halo`in the nodule does not exclude malignancy. Due to the presence of lymph node involvement in PTMC in all children with PTC total thyroidectomy should be performed with lymph nodes verification.

Hyperthyroidism After Allogeneic Hematopoietic Stem Cell Transplantation: A Report of Four Cases

PubMed Central

Sağ, Erdal; Gönç, Nazlı; Alikaşifoğlu, Ayfer; Kuşkonmaz, Barış; Uçkan, Duygu; Özön, Alev; Kandemir, Nurgün

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves’ disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation. PMID:26777050

Down syndrome, insulin-dependent diabetes mellitus and hyperthyroidism: a rare association.

PubMed

Marques, Inês; Silva, Ana; Castro, Sofia; Lopes, Lurdes

2015-06-29

The association between Down syndrome (DS) and autoimmune endocrinopathies is well established. These disorders become increasingly frequent as children grow older and the onset of one often predisposes to the development of others. However, there are few cases in the literature reporting the simultaneous onset of type 1 diabetes mellitus and hyperthyroidism in children with DS. We describe a case of an 8-year-old girl with DS who presented at the emergency department with hyperglycaemia and ketosis as a primary manifestation of type 1 diabetes mellitus. During the initial investigation, hyperthyroidism was detected, with thyroid-stimulating hormone<0.01 µUI/mL, positive antithyroid antibodies and an increase in thyroid gland on ultrasound. The authors present this case to underline the usefulness of monitoring thyroid function at the diagnosis of diabetes, even without apparent clinical manifestations, and to alert for the possibility of autoimmune endocrine dysfunction in children with DS. 2015 BMJ Publishing Group Ltd.

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient.

PubMed

Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

2011-08-11

A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case.

Pegylated interferon de novo-induce autoimmune haemolytic anaemia in chronic hepatitis C patient

PubMed Central

Said, Ashraf; Elbahrawy, Ashraf; Alfiomy, Mohamed; Abdellah, Mohamed; Shahat, Khaled; Salah, Mohamed; Mostafa, Sadek; Elwassief, Ahmed; Aboelfotoh, Attef; Abdelhafeez, Hafez; El-Sherif, Assem

2011-01-01

A 55-year-old Egyptian woman with chronic hepatitis C undergoing treatment with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin was referred to our hospital on November 2010 with prolonged easy fatigability and an attack of syncope; she had no prior history of autoimmune disorders or allergy. Laboratory investigations documented the presence of Peg-IFN induced autoimmune haemolytic anaemia and autoimmune thyroiditis. Intravenous γ globulin (IVGG) failed to correct the autoimmune process; on the other hand steroid therapy dramatically corrected both haematological and thyroid values, and step down the immune process. Our report indicated that Peg-IFN de novo-induce autoimmune haemolysis, documenting a previous report. IVGG failed to step down the immune process in our case. PMID:22688484

Pathogenesis of Hyperthyroidism.

PubMed

Singh, Ishita; Hershman, Jerome M

2016-12-06

Hyperthyroidism is a form of thyrotoxicosis in which there is excess thyroid hormone synthesis and secretion. Multiple etiologies can lead to a common clinical state of "thyrotoxicosis," which is a consequence of the high thyroid hormone levels and their action on different tissues of the body. The most common cause of thyrotoxicosis is Graves' disease, an autoimmune disorder in which stimulating thyrotropin receptor antibodies bind to thyroid stimulating hormone (TSH) receptors on thyroid cells and cause overproduction of thyroid hormones. Other etiologies include: forms of thyroiditis in which inflammation causes release of preformed hormone, following thyroid gland insult that is autoimmune, infectious, mechanical or medication induced; secretion of human chorionic gonadotropin in the setting of transient gestational thyrotoxicosis and trophoblastic tumors; pituitary thyrotropin release, and exposure to extra-thyroidal sources of thyroid hormone that may be endogenous or exogenous. © 2017 American Physiological Society. Compr Physiol 7:67-79, 2017. Copyright © 2017 John Wiley & Sons, Inc.

DYSMICROBISM, INFLAMMATORY BOWEL DISEASE AND THYROIDITIS: ANALYSIS OF THE LITERATURE.

PubMed

Tomasello, G; Tralongo, P; Amoroso, F; Damiani, P; Sinagra, E; Noto, M; Arculeo, V M; Jurjus Zein, R; Saad, W; Jurjus, A; Gerbino, A; Leone, A

2015-01-01

The human body is colonized by a large number of microbes that are collectively referred to as the microbiota. They interact with the hosting organism and some do contribute to the physiological maintenance of the general good health thru regulation of some metabolic processes while some others are essential for the synthesis of vitamins and short-chain fatty acids. The abnormal variation, in the quality and/or quantity of individual bacterial species residing in the gastro-intestinal tract, is called “dysmicrobism”. The immune system of the host will respond to these changes at the intestinal mucosa level which could lead to Inflammatory Bowel Diseases (IBD). This inflammatory immune response could subsequently extend to other organs and systems outside the digestive tract such as the thyroid, culminating in thyroiditis. The goal of the present study is to review and analyze data reported in the literature about thyroiditis associated with inflammatory bowel diseases such as Ulcerative Colitis (UC) and Crohn’s Disease (CD). It was reported that similarities of some molecular bacterial components with molecular components of the host are considered among the factors causing IBD through an autoimmune reaction which could involve other non-immune cell types. The axis dysmicrobism-IBD-autoimmune reaction will be investigated as a possible etiopathogenic mechanism to Autoimmune Thyroiditis. If such is the case, then the employment of specific probiotic strains may represent a useful approach to moderate the immune system.

[Coexistence of Addison-Biermer's disease with autoimmune thyroiditis - case report].

PubMed

Lacka, Katarzyna; Maciejewski, Adam; Florczak-Wyspiańska, Jolanta

2013-01-01

Addison-Biermer's anaemia is an autoimmune disease and the most common cause of vitamin B12 deficiency. Hashimoto disease is the most common type of the thyroiditis and also has autoimmunological origin. Frequent coexistence of both mentioned entities has been observed. In the paper we report a case of a woman, who was diagnosed with pernicious anaemia (PA) with predominant neurological symptoms and concomitant autoimmune thyroiditis. Many efforts have been made in order to explain frequent coexistence of mentioned diseases. Both genetic (mainly HLA region genes) and environmental (mostly bacterial infections) factors are considered. The aim of the study (was to emphasize significance of diagnosing thyroid gland diseases among PA patients. It is also important to remember that neurological symptoms are frequent in the course of PA and may precede other complaints. However it should not prevent the right diagnosis.

Elevated interleukin-1β in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

PubMed

Sun, Li; Zhang, Xiaoxu; Dai, Fang; Shen, Jijia; Ren, Cuiping; Zuo, Chunlin; Zhang, Qiu

2016-08-01

To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT. Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

[Diagnostic difficulties in Grave's orbitopathy--case report].

PubMed

Jedrzejowski, Maciej; Grzesiuk, Wiesław; Szwejda, Elzbieta; Bar-Andziak, Ewa

2004-03-01

Graves' orbitopathy is caused by intraorbital inflammatory reaction due to autoimmune thyroid disease. In most cases the diagnosis is based on the coexistence of typical eye signs and hyperthyroidism symptoms. In presented case, the absence of thyroid dysfunction implicated performance of differential diagnosis. Among many available diagnostic tools nuclear magnetic resonance seems to be the most accurate in confirmation of diagnosis of Graves' orbitopathy.

Hashimoto thyroiditis with an unusual presentation of cardiac tamponade in Noonan syndrome.

PubMed

Lee, Mi Ji; Kim, Byung Young; Ma, Jae Sook; Choi, Young Earl; Kim, Young Ok; Cho, Hwa Jin; Kim, Chan Jong

2016-11-01

Noonan syndrome is an autosomal dominant, multisystem disorder. Autoimmune thyroiditis with hypothyroidism is an infrequent feature in patients with Noonan syndrome. A 16-year-old boy was admitted because of chest discomfort and dyspnea; an echocardiogram revealed pericardial effusion. Additional investigations led to a diagnosis of severe hypothyroidism due to Hashimoto thyroiditis. The patient was treated with L-thyroxine at 0.15 mg daily. However, during admission, he developed symptoms of cardiac tamponade. Closed pericardiostomy was performed, after which the patient's chest discomfort improved, and his vital signs stabilized. Herein, we report a case of an adolescent with Noonan syndrome, who was diagnosed with Hashimoto thyroiditis with an unusual presentation of cardiac tamponade.

Exposure to DBP and High Iodine Aggravates Autoimmune Thyroid Disease Through Increasing the Levels of IL-17 and Thyroid-Binding Globulin in Wistar Rats.

PubMed

Duan, Jiufei; Kang, Jun; Deng, Ting; Yang, Xu; Chen, Mingqing

2018-05-01

Autoimmune thyroid disease (AITD) is the most common autoimmune disease that causes hypothyroidism. High iodine is a well-known factor that can induce thyroid disorders, including Hashimoto's thyroiditis, one of the main types of AITD. Recent epidemiological studies have indicated that phthalates, especially di-n-butyl phthalate (DBP) may induce thyroid disease. In this study, we aim to determine the effects and underlying mechanisms of high iodine and/or DBP exposure on AITD. Female Wistar rats were modeled with thyroglobulin and exposed to high iodine and/or DBP. We investigated histopathological changes in the thyroid and measured thyroid hormone levels in serum to assess thyroid function. In the thyroid and liver, we detected oxidative stress, proinflammatory factors (IL-1β, IL-6, and IL-17) and the activation of activator protein 1 (AP-1), a transcription factor that is related to the synthesis of the thyroxine-binding globulin (TBG) and the activation of Th17. After blocking AP-1 with SP600125, we detected TBG and the Th17 related cytokines (IL-6 and IL-17). The data showed that thyroid damage and the alteration of thyroid hormones were greater when the rats were exposed to both high iodine and DBP. Coexposure to DBP and high iodine enhanced the activation of AP-1 in the liver and thyroid, and induced an increase in the levels of TBG in serum and IL-17 in the thyroid. Blocking AP-1 activation prevented the increase of TBG and IL-17. The results indicate that high iodine and/or DBP exposure exacerbated AITD through altering TBG levels in serum and aggravating IL-17 in the thyroid.

The Effect of Ezetimibe/Statin Combination and High-Dose Statin Therapy on Thyroid Autoimmunity in Women with Hashimoto's Thyroiditis and Cardiovascular Disease: A Pilot Study.

PubMed

Krysiak, R; Szkróbka, W; Okopień, B

2016-10-01

Background: Intensive statin therapy was found to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis. No similar data are available for other hypolipidemic agents. Methods: The participants of the study were 16 women with Hashimoto's thyroiditis and coronary artery disease. On the basis of statin tolerance, they were divided into 2 groups. 8 patients who did not tolerate high-dose statin therapy were treated with a statin, the dose of which was reduced by half, together with ezetimibe. The remaining 8 patients tolerating the treatment continued high-dose statin therapy. Plasma lipids, serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: Replacing high-dose statin therapy with ezetimibe/statin combination therapy increased serum titers of thyroid peroxidase as well as led to an insignificant increase in serum titers of thyroglobulin antibodies. At the end of the study, thyroid peroxidase and thyroglobulin antibody titers were higher in patients receiving the combination therapy than in those treated only with high-dose statin. Conclusions: Our study shows that high-dose statin therapy produces a stronger effect on thyroid autoimmunity than ezetimibe/statin combination therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Thyrotropin-secreting pituitary adenoma in an 11-year-old boy with type 1 autoimmune polyglandular syndrome.

PubMed

Mazerkina, Nadia; Trunin, Yuri; Gorelyshev, Sergey; Golanov, Andrey; Kadashev, Boris; Shishkina, Liudmila; Rotin, Daniil; Karmanov, Maxim; Orlova, Elizabet

2016-02-01

Thyrotropinomas (TSHomas) are rare pituitary adenomas, particularly in childhood. We present here the case of an 11-year-old boy with type 1 autoimmune polyglandular syndrome (APS1) and TSHoma which was diagnosed by elevated thyroid - stimulating hormone and thyroid hormones levels without evident clinical signs of hyperthyroidism. He was underwent partial resection of the tumor via transsphenoidal approach and subsequently radiation therapy. Consequently, 1 year after radiotherapy, the patient developed growth hormone deficiency, three and half years after radiation became euthyroid, and five and half years after treatment - hypothyroid. This is the first case of the coexistence of these two rare endocrine diseases in one patient.

Common autoimmune biomarkers, thyroid hormonal abnormalities, and beta cells dysfunction in patients with latent autoimmune diabetes in adults with type II diabetes mellitus.

PubMed

Yousefzadeh, Gholamreza; Gozashti, Mohammadhossein; Najafipour, Hamid; Gholamhosseinian, Najar Ahmad; Bahramnejad, Abbas; Shokouhi, Mostafa

2016-01-01

Latent autoimmune diabetes in adults (LADA) is autoimmune diabetes with a slow progression characterized by the presence of antibodies associated with Type I diabetes. The present study aimed to assess autoimmune characteristics in patients with LADA in Iran. We attempted to obtain a clear view of autoimmune conditions in LADA among our population. This study was sourced from the population-based survey of KERCARDS aiming assessment of cardiovascular risk factors among a great sample of Iranian population who were resident in Kerman, a great province in southern Iran. Among all diabetic patients who were negative for Anti Glutamic Acid Decarboxylase (GAD) antibody test, 120 were selected as the controls and among 80 patients who were positive for this test diagnosed as LADA, the recorded files of 57 patients were complete considered as the cases. The level of thyroxin is significantly lower in patients with LADA compared with the controls so 73.7% and 45% of patients had normal level of thyroxin, respectively. Also, those with LADA had considerably lower levels of both thyroid peroxydaseantibody (TPO-Ab) and C-peptide when compared with non-LADA group. Using multivariate analyses and with the presence of baseline variables including gender, age, and duration of disease, the diagnosis of LADA was associated with lower serum levels of Anti-TPO, C-peptide, and thyroxin, but not associated with the level of Anti-TTG in serum. LADA patients may face with lower serum levels of C-peptide and thyroid-specific antibodies indicating insulin therapy requirement and authoimmune fundaments of the disease, respectively. Copyright © 2016. Published by Elsevier Ltd.

Familial juvenile autoimmune hypothyroidism, pituitary enlargement, obesity, and insulin resistance.

PubMed

Reutrakul, Sirimon; Hathout, Eba H; Janner, Donald; Hara, Manami; Donfack, Joseph; Bass, Joseph; Refetoff, Samuel

2004-04-01

The proband, a 9-year-old Hispanic female, presented with hair loss, strabismus, and weight gain. On magnetic resonance imaging (MRI) she was found to have severe primary hypothyroidism and a large pituitary mass. In addition, acanthosis nigricans, obesity, and hyperinsulinism were observed. Findings were similar in three of four siblings. Thyroid peroxidase antibodies were detected in the father and three of four siblings. Although all family members were obese, and hyperinsulinemia with high proinsulin and C-peptide was found in all except one sibling, only the mother and one child had overt type 2 diabetes mellitus. Because of the unusual association of autoimmune thyroid disease, insulin resistance and obesity rather than insulin deficiency, we searched for possible genetic abnormalities. The HLA haplotypes did not cosegregate with autoimmune thyroid disease or insulin resistance. Mutational analysis of known obesity genes was done. Leptin was not deficient, and sequencing of the proband's DNA showed no mutations in the perixisome proliferator activated receptor (PPAR)-gamma, PPAR-gamma(2), PPAR-alpha or melanocortin 4 receptor genes. Maternally inherited diabetes and deafness was ruled out since no mutations were found in mitochondria DNA. Insulin receptor antibodies were not detected. In conclusion, the remarkably high incidence of childhood autoimmune hypothyroidism, pituitary enlargement, insulin resistance and obesity in this family is not linked to known HLA types or known gene defects.

[Clinical features of myasthenia gravis with thyroid disease with 106 patients].

PubMed

Meng, Chao; Jing, Yun; Li, Ran; Zhang, Xiaojun; Wang, Jiawei

2016-03-22

To report the presentation, clinical course and prognosis of myasthenia gravis (MG) with thyroid disease. Retrospective data analysis was conducted.Between 2004 and 2013, we reviewed a total of 106 patients with MG. We analyzed the clinical features, the relationship between the thyroid function, antibodies and the clinical course, prognosis. (1) In our study, 20/106 (18.87%) patients were thyroid function-abnormal, 37/106 (34.91) were thyroglobulin antibodies (TGAb) and/or thyroid microsomal antibody (TMAb)-positive, and abnormality was observed in 46 (43.40%) of the thyroid gland. Thyroid antibody positive rate was higher than abnormal thyroid function rate, and the difference was significant (P=0.036). (2) The thyroid stimulating hormone (TSH) level ((2.9±4.0) mIU/L) of ocular MG was higher than the level ((1.5±1.1) mIU/L) of generalized MG (P=0.01). (3) The transformation time of 52 ocular type to generalized type was longer in higher antibody group than in normal group (P=0.04). And there were no significant differences between the elevated TSH type and the normal TSH type, the abnormal thyroid function type and normal thyroid function type, the abnormal thyroid type and the normal thyroid type. (4) Comparing the TSH level, total antibody level, TGAb, and TMAb level between the ease group and the unease group in the course of 1 year, 2 years, 5 years, there were no significant differences (all P>0.05). MG is often companied with thyroid abnormalities. MG patients are more susceptible to hashimoto thyroiditis and other autoimmune thyroid diseases. Ocular type patients are more likely to suffer from thyroid function decrease than the generalized type. MG patients with hashimoto thyroiditis and other autoimmune thyroid diseases are more sensitive to respond to therapy means like glucocorticoid therapy, and the short-term prognosis is relatively good. There are no significant correlations between the MG remission rate and TSH level, total antibody level, TGAb and TMAb level.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

PubMed

Mocellin, Ramon; Walterfang, Mark; Velakoulis, Dennis

2007-01-01

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

PubMed

Januś, D; Wójcik, M; Drabik, G; Wyrobek, Ł; Starzyk, J B

2018-03-01

The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

[Rare differential diagnosis of hyperthyroidism].

PubMed

Besemer, Britta; Müssig, Karsten

2016-06-01

A 54-year-old female patient is admitted for evaluation of her thyroid function after two cycles of ipilimumab therapy. The decision for the anti-cytotoxic-T-lymphocyte-antigen-4-therapy (anti-CTLA-4) was made two months earlier because of malignant melanoma with pulmonary metastases. The patient was euthyroid before initiation of treatment and without known thyroid disease. The laboratory reveals thyrotoxicosis with elevated anti-thyroid peroxidase and anti-thyroglobulin antibody levels. The anti-thyroid stimulating hormone receptor antibody levels are within the normal range. Thyroid ultrasound shows a normal-sized, inhomogenous, hypoechogenic thyroid gland, consistent with autoimmune thyroiditis. Diagnosis of hyperthyroidism due to ipilimumab-induced autoimmune thyroiditis is made. The patient does not receive any thyroid-specific medication, with regular control of the thyroid hormone levels. When the patient becomes euthyroid, the ipilimumab therapy is continued. Three weeks later, the patient develops hypothyroidism and a supplementation with L-thyroxine is initiated. An anti-CTLA-4 therapy may cause thyroid dysfunction. Therefore, before initiation and in the course of the treatment, regular controls of the thyroid hormone levels are required. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

PubMed

Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

2014-12-01

The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B titers, as well as a history of more frequent throat infections than controls (p<0.0001). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease or organ- and nonorgan-specific autoimmunity seem not more frequent in children and adolescents with PANDAS than in healthy controls. A potential relationship between autoimmunity and PANDAS should be assessed further in larger studies. Children and adolescents with PANDAS should not be actually screened for thyroid function, celiac disease and/or autoimmune diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18.

PubMed

Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christidis, M; Sarri, C; Karadima, G; Petersen, M B; Xaidara, A; Kanariou, M; Nicolaidou, P

1999-02-01

A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.

Association of vitamin D insufficiency/deficiency with thyroid artery Doppler ultrasonography in patients with Hashimoto thyroiditis.

PubMed

Nalbant, Ahmet; Aydin, Ayhan; Karacan, Alper; Onmez, Attila; Tamer, Ali; Cinemre, Hakan

2017-01-01

During the course of the autoimmune thyroid diseases, ultrasonography change parallel to histopathology. Vitamin D is associated with autoimmune diseases and thus can affect thyroid blood flow. Our aim was to investigate the relationship between vitamin D insufficiency/deficiency and thyroid hemodynamic indices in patients with Hashimoto thyroiditis. A total of 93 patients who presented to Sakarya University Endocrinology outpatient clinic from April to September 2016 and diagnosed with Hashimoto thyroiditis were included in this study. Clinical and serologic data, thyroid antibodies and 25(OH)D3 were evaluated. Mean peak systolic velocity(mPSV), mean end-diastolic velocity (EDV), mean resistive index (RI) flows of superior and inferior thyroid arteries were measured with B-mode Doppler ultrasonography. Vitamin D insufficiency/deficiency was detected in 59 (63.4%). TPO Ab and TgAb levels were found higher in patients with vitamin D insufficiency/deficiency. In the normal vitamin D group, superior thyroid artery mPSV (32.21±6.73cm/s) and EDV(13.27±2.80 cm/s) were higher than in the low vitamin D group [mPSV (28.32±8.99cm/s) and EDV(10.67±3.68 cm/s)] (P=0.034, P=0.001, respectively). Inferior thyroid artery EDV value was higher in the normal compared to the low vitamin D group (0.032). RI measured in all arteries were higher in the vitamin D insufficient/deficient group compared to the Vitamin D normal group (p=0.001). Vitamin-D insufficiency/deficiency has led to reduced parenchymal blood supply and increased micro-vascular resistance in Hashimoto thyroiditis patients.

Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study.

PubMed

Guo, Qingling; Wu, Dan; Yu, Huixin; Bao, Jiandong; Peng, Shiqiao; Shan, Zhongyan; Guan, Haixia; Teng, Weiping

2018-03-01

Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3 + T and CD19 + B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction. Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases. Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.

Thyroid Autoantibodies Are Rare in Nonhuman Great Apes and Hypothyroidism Cannot Be Attributed to Thyroid Autoimmunity

PubMed Central

Aliesky, Holly; Courtney, Cynthia L.; Rapoport, Basil

2013-01-01

The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was previously reported in 4 individual nonhuman great apes. However, there is scarce information on normal serum thyroid hormone levels and virtually no data for thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone levels and TSH in all nonhuman great ape genera including adults, adolescents, and infants. Because hypothyroidism in humans is commonly the end result of thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH receptor (TSHR). We established a thyroid hormone and TSH database in orangutans, gorillas, chimpanzees, and bonobos (447 individuals). The most striking differences are the greatly reduced free-T4 and free-T3 levels in orangutans and gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest living human relatives. Moreover, thyroid autoantibodies are rare and hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes. PMID:24092641

Ultrasound sonoelastography in the evaluation of thyroiditis and autoimmune thyroid disease.

PubMed

Ruchała, Marek; Szmyt, Krzysztof; Sławek, Sylwia; Zybek, Ariadna; Szczepanek-Parulska, Ewelina

2014-01-01

Sonoelastography (USE) is a constantly evolving imaging technique used for the noninvasive and objective estimation of tissue stiffness. Several USE methods have been developed, including Quasi-Static or Strain Elastography and Shear Wave Elastography. The utility of USE has been demonstrated in differentiating between malignant and benign thyroid lesions. Recently, USE has been applied in the evaluation of thyroiditis and autoimmune thyroid disease (AITD).Thyroid inflammatory illnesses constitute a diverse group of diseases and may manifest various symptoms. These conditions may share some parallel clinical, biochemical, and ultrasonographic features, which can lead to diagnostic difficulties. USE may be an additional tool, supporting other methods in the diagnosis and treatment monitoring of thyroid diseases, other than thyroid nodular disease.The aim of this article was to analyse and summarise the available literature on the applicability of different elastographic techniques in the diagnosis, differentiation and monitoring of various types of thyroiditis and AITD. Advantages and limitations of this technique are also discussed.

Genetic Factors of Autoimmune Thyroid Diseases in Japanese

PubMed Central

Ban, Yoshiyuki

2012-01-01

Autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are caused by immune response to self-thyroid antigens and affect approximately 2–5% of the general population. Genetic susceptibility in combination with external factors, such as smoking, viral/bacterial infection, and chemicals, is believed to initiate the autoimmune response against thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITDs. Various techniques have been employed to identify genes contributing to the etiology of AITDs, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked to AITDs, and, in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to GD and HT and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. Known AITD-susceptibility genes are classified into three groups: HLA genes, non-HLA immune-regulatory genes (e.g., CTLA-4, PTPN22, and CD40), and thyroid-specific genes (e.g., TSHR and Tg). In this paper, we will summarize the latest findings on AITD susceptibility genes in Japanese. PMID:22242199

Thyroid disease and the nervous system.

PubMed

Wood-Allum, Clare A; Shaw, Pamela J

2014-01-01

Thyroid disorders are common in the general population and in hospitalized patients. Thyroid disease may present first with neurological complications or else may occur concurrently in patients suffering other neurological disorders, particularly those with an autoimmune etiology. For this reason neurologists will commonly encounter patients with thyroid disease. This chapter provides an overview of the neurological complications and associations of disorders of the thyroid gland. Particular emphasis is placed on conditions such as thyrotoxic periodic paralysis and myxedema coma in which the underlying thyroid disorder may be occult leading to a first, often emergency, presentation to a neurologist. Information about clinical features, diagnosis, pathogenesis, therapy, and prognosis is provided. Emphasis is placed on those aspects most likely to be relevant to the practicing neurologist and the interested reader is directed to references to good, recent review articles for further information. © 2014 Elsevier B.V. All rights reserved.

Interception of the development of self tolerance in fetal lambs.

PubMed

McCullagh, P

1989-08-01

Investigation of the nature of immunological self tolerance has usually relied upon experimental protocols in which the tolerant state is interrupted in mature animals with the production of autoimmune disease. While such research has improved the understanding of those processes operative in overt autoimmunity, it has not been informative in relation to events associated with the establishment of self tolerance. Any description of this state which is to be based on observation will necessitate the use of experimental systems that permit observation of animals during the development of self tolerance. The present experiment entailed intervention approximately one third of the way through the gestation period of fetal lambs. An earlier experiment had established that 54-day fetal lambs would accept allografts of adult skin. This indicated that the capacity to discriminate between self and non-self had not been acquired at that age. Fetuses at this stage of gestation were submitted to either partial or total removal of the thyroid gland. The excised tissue was then implanted in nude mice for periods of 5 to 9 weeks. It was subsequently replaced subcutaneously, either in the original donor or in another fetus at a comparable stage of gestation. At postmortem examination, several weeks later, self implants in lambs from which the thyroid gland had been completely removed displayed autoimmune thyroiditis of varying degrees of severity. However, self implants in partially thyroidectomized animals were uniformly free from autoimmune manifestations. This implied that these reactions had not been directed against contaminating murine tissues in the implants replaced in completely thyroidectomized lambs. All allogeneic implants were subject to vey heavy lymphocytic infiltration, usually with accompanying necrosis consistent with allograft rejection. This was taken as an indication that hypothyroid fetal lambs had become immunocompetent by the time of thyroid reimplantation. Spontaneous immunological reactivity against reimplanted self thyroid tissue by thyroidectomized lambs was interpreted as a failure to acquire the capacity for self recognition as a result of antigen deprivation.

Exacerbation of Autoimmune Thyroiditis by CTLA-4 Blockade: A Role for IFNγ-Induced Indoleamine 2, 3-Dioxygenase

PubMed Central

Sharma, Rajni; Di Dalmazi, Giulia

2016-01-01

Background: Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) is a negative regulator of immune responses that suppresses the activity of effector T cells and contributes to the maintenance of self tolerance. When blocked therapeutically, CTLA-4 leads to an overall activation of T cells that has been exploited for cancer control, a control associated however with a variety of immune-related side effects such as autoimmune thyroiditis. To investigate the mechanism(s) underlying this form of thyroiditis, we used the NOD-H2h4 mouse, a model that develops thyroiditis at very high incidence after addition of iodine to the drinking water. Methods: NOD-H2h4 mice were started on drinking water supplemented with 0.05% sodium iodide when 8 weeks old and then injected with a hamster monoclonal antibody against mouse CTLA-4, polyclonal hamster immunoglobulins, or phosphate buffered saline when 11 weeks old. One month later (15 weeks of age), mice were sacrificed to assess thyroiditis, general immune responses in blood and spleen, and expression of indoleamine 2, 3-dioxygenase (IDO) in the thyroid and in isolated antigen-presenting cells after stimulation with interferon gamma. The study also analyzed IDO expression in four autopsy cases of metastatic melanoma who had received treatment with a CTLA-4 blocking antibody, and six surgical pathology Hashimoto thyroiditis controls. Results: CTLA-4 blockade worsened autoimmune thyroiditis, as assessed by a greater incidence, a more aggressive mononuclear cell infiltration in thyroids, and higher thyroglobulin antibody levels when compared to the control groups. CTLA-4 blockade also expanded the proportion of splenic CD4+ effector T cells, as well as the production of interleukin (IL)-2, interferon gamma, IL-10, and IL-13 cytokines. Interestingly, CTLA-4 blockade induced a strong expression of IDO in mouse and human thyroid glands, an expression that could represent a counter-regulatory mechanism to protect against the inflammatory environment. Conclusions: This study shows that CTLA-4 blockade exacerbates the iodine-accelerated form of thyroiditis typical of the NOD-H2h4 mouse. The study could also have implications for cancer patients who develop thyroiditis as an immune-related adverse event after CTLA-4 blockade. PMID:27296629

Myxedema coma: A case report of pediatric emergency care.

PubMed

Zhu, Yueniu; Qiu, Wenjuan; Deng, Mengyan; Zhu, Xiaodong

2017-05-01

Myxedema coma (MC) is extremely rare but lethal in pediatric patients with hypothyroidism leading to altered mental status and hypothermia. But there is no clinical guideline for such cases. A 6-year-old Chinese girl presented with coma and hypothermia preceded by pneumonia. Her lab results were: free thyroxin (T4) 4.18 pmol/L and thyroid-stimulating hormone (TSH) > 150 μIU/mL with extremely elevated anti-thyroid peroxidase (TPO-Ab) and anti-thyroglobulin. Pneumonia, mild pleural, and pericardial effusion were seen on computed tomographic (CT) scan. MC, autoimmune hypothyroidism, pneumonia and sepsis were diagnosed. Gastric levothyroxine, intravenous dexamethasone and antibiotics were administered. Her consciousness was restored and temperature returned to normal 2 days after starting levothyroxine. She was discharged two weeks later. MC is rare but may be the initial presentation in pediatric patients with prolonged untreated hypothyroidism. Autoimmune thyroiditis could cause hypothyroidism in children. MC should be suspected in pediatric patients with altered mental status, hypothermia and cardiovascular instability. Treatment with 100 mg/m of gastric levothyroxine is an option for pediatric patients with MC.

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure

PubMed Central

Triggianese, P; Perricone, C; Conigliaro, P; Chimenti, MS; Perricone, R; De Carolis, C

2015-01-01

Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only in the presence of TAI but also in the presence of non-autoimmune thyroid disorders. PMID:26657164

[Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

PubMed

Krysiak, Robert; Okopień, Bogusław

2015-01-01

Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

PubMed

Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

2014-01-01

Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.

[Alpha interferon induced hyperthyroidism: a case report and review of the literature].

PubMed

Maiga, I; Valdes-Socin, H; Thiry, A; Delwaide, J; Sidibe, A T; Beckers, A

2015-01-01

Treatment with alpha interferon in hepatitis C triggers a thyroid autoimmunity in a variable percentage of cases (2-8%). This complication raises some questions about its screening, the possibility to continue anti-viral therapy and thyroid treatment. Alpha interferon has an immunomodulatory effect on the thyroid, but also an inhibitory effect on thyroid hormone synthesis. This explains the occurrence of cases of thyroid dysfunction, which often remain undetected because of their latency. Factors predicting thyroid dysfunction with interferon use are: female sex, history of thyroid disease and previous autoimmunity. Several clinical aspects are encountered including hypothyroidism (the most frequent depending on the series) and hyperthyroidism related to Graves' disease. For their detection, a cooperation between general practionners, gastroenterologists and endocrinologists is mandatory thyroid function tests are requested before, during and after treatment,with alpha interferon. Therapeutic aspects of thyroid disorders range from simple monitoring to symptomatic treatment, such as thyroxine prescription in the presence of hypothyroidism. Antithyroid drugs radioactive iodine or thyroid surgery are used in cases of severe or persistent Graves' disease induced by alpha interferon.

The Genetics of Autoimmune Thyroiditis: the first decade

PubMed Central

Rose, Noel R.

2011-01-01

Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (MHC), the interplay of different subregions within the MHC in promoting or retarding development of disease, the differing roles of MHC class II and MHC I class genes in induction and effector phases, respectively, and the cumulative effect of non-MHC genes, each of which represents a small addition to overall susceptibility. Other experiments revealed that genetic differences in thyroglobulin allotypes influence susceptibility to thyroiditis. Thyroid glands differed in different strains in vulnerability to passive transfer of antibody. The first evidence of modulatory genes on the sex-related X chromosome emerged. All of these genetic findings were concurrently translated to the human disease, Hashimoto’s thyroiditis, where thyroglobulin is also the initiating antigen. PMID:21683550

Immunological profiles in alopecia areata.

PubMed

Galbraith, G M; Thiers, B H; Vasily, D B; Fudenberg, H H

1984-02-01

Cell-mediated immunity and auto-immune phenomena were investigated in sixty patients with active alopecia areata of various degrees of severity. Serum auto-antibodies to thyroid antigens were detected in twenty-three patients. Examination of T-lymphocyte populations, lymphocyte DNA synthesis, and lymphokine production in response to mitogen stimulation revealed no differences between the sixty patients and matched healthy control subjects. However, patients with thyroid auto-immunity and/or the presence of alopecia totalis or universalis showed significant reductions in interactive T lymphocytes (recognized by rosette formation with human B lymphoblastoid cells) and diminished production of leukocyte migration inhibition factor in response to stimulation with phytohaemagglutinin. This suggests that immune mechanisms may be involved in the pathogenesis of alopecia areata which is associated with thyroid auto-immunity or which progresses to total hair loss.

A selective memory deficit caused by autoimmune encephalopathy associated with Hashimoto thyroiditis.

PubMed

Koros, Christos; Economou, Alexandra; Mastorakos, George; Bonakis, Anastasios; Kalfakis, Nikolaos; Papageorgiou, Sokratis G

2012-09-01

We report a longstanding selective memory deficit in a euthyroid 45-year-old woman who was being treated with levothyroxine for Hashimoto thyroiditis. The patient had complained of memory problems and deterioration of her concentration skills for about 2 years. Her endocrinologist thought that she was depressed. The patient's physical examination was normal. She scored a full 30 points on the Mini-Mental State Examination, but neuropsychological evaluation showed a significant deficit in her verbal memory. Routine blood tests and cerebrospinal fluid analysis showed only antithyroid peroxidase antibodies. Brain magnetic resonance imaging was normal. Electroencephalogram showed scarce intermittent bilateral multifocal theta waves. We increased the patient's daily dose of levothyroxine and started her on dexamethasone therapy. Five months later, we repeated the entire evaluation and found both her cognitive function and her electroencephalogram to be normal. Autoimmune encephalopathy associated with Hashimoto thyroiditis is already known to present with either stroke-like episodes or diffuse progressive deterioration. Our patient shows that the encephalopathy can present as a chronic selective memory deficit that can spare executive functions and short-term memory. This presentation can be missed or mistaken for depression, but can be diagnosed with a detailed neuropsychological evaluation.

Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders

PubMed Central

Yang, Deng-Ho; Ho, Ling-Jun; Lai, Jenn-Haung

2014-01-01

During the course of chronic hepatitis C virus (HCV) infection, various extrahepatic manifestations of autoimmune disorders may occur, including arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid dysfunction. In addition, the prevalence of circulating autoantibodies is high among patients with HCV infection. Commonly detected autoantibodies in HCV-infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection. A possible reason for antibody production is overactivation and proliferation of B lymphocytes, via the interaction with the surface protein of HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided. This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection. PMID:24659887

Granulomatous Thyroiditis: A Case Report and Literature Review.

PubMed

Trivedi, Darshan P; Bhagat, Ramesh; Nakanishi, Yukihiro; Wang, Alun; Moroz, Krzysztof; Falk, Nadja K

2017-09-01

Granulomatous disease in the thyroid gland has been linked to viral, bacterial and autoimmune etiologies. The most common granulomatous disease of the thyroid is subacute granulomatous thyroiditis, which is presumed to have a viral or post-viral inflammatory cause. Bacterial etiologies include tuberculosis, actinomycosis, and nocardiosis, but are extremely rare. Disseminated actinomycosis and nocardiosis more commonly affect organ-transplant patients with the highest susceptibility within the first year after transplant surgery. A 45-year-old African American male, who received his third kidney transplant for renal failure secondary to Alport Syndrome, presented with numerous subcutaneous nodules and diffuse muscle pain in the neck. Further workup revealed bilateral nodularity of the thyroid. Fine needle aspiration of these nodules demonstrated suppurative granulomatous thyroiditis. Subsequent right thyroid lobectomy showed granulomatous thyroiditis with filamentous micro-organisms, morphologically resembling Nocardia or Actinomyces. Disseminated granulomatous disease presenting in the thyroid is very rare, and typically afflicts immune-compromised patients. The overall clinical, cytologic and histologic picture of this patient strongly points to an infectious etiology, likely Nocardia, in the setting of recent organ transplantation within the last year. © 2017 by the Association of Clinical Scientists, Inc.

Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity

PubMed Central

Ponto, K A; Schuppan, D; Zwiener, I; Binder, H; Mirshahi, A; Diana, T; Pitz, S; Pfeiffer, N; Kahaly, G J

2014-01-01

Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid–eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P < 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were ‘protective’ for GD and thus linked to HT, OR = 0·49 (P < 0·001), 0·06 (P < 0·001), 0·25 (P < 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P < 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P < 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P < 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO. PMID:24903731

Thyroid function and autoimmunity in children and adolescents with Type 1 Diabetes Mellitus.

PubMed

Riquetto, Aline Dantas Costa; de Noronha, Renata Maria; Matsuo, Eliza Mayumi; Ishida, Edson Jun; Vaidergorn, Rafael Eliahu; Soares Filho, Marcelo Dias; Calliari, Luis Eduardo Procópio

2015-10-01

We evaluated 233 children and adolescents with T1 Diabetes to analyze the prevalence and characteristics of Autoimmune Thyroid Disease. AITD was found in 23%, the majority being female and patients older than 5 years of age. Screening is mandatory, and the best approach could be guided by gender and age. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Susceptibility to thyroid disorders in hepatitis C.

PubMed

Muratori, Luigi; Bogdanos, Dimitrios P; Muratori, Paolo; Lenzi, Marco; Granito, Alessandro; Ma, Yun; Mieli-Vergani, Giorgina; Bianchi, Francesco B; Vergani, Diego

2005-06-01

Autoimmune thyroid disorders (AITDs) are reported, especially during interferon treatment, in chronic HCV infection, in which non-organ-specific autoantibodies (NOSAs) are common. We wondered whether seropositivity for NOSA is associated with susceptibility to AITDs. We evaluated thyroid function and antithyroglobulin and antithyroperoxidase antibodies in 348 Italian patients with chronic hepatitis C (34% NOSA-positive), 196 patients (33% NOSA-positive) of whom received interferon treatment. At baseline, thyroid disorders were significantly more frequent in liver/kidney microsomal antibody type 1 (LKM1)-positive patients (29% vs 9%, P < .005). Similarly, on interferon therapy de novo autoimmune thyroid markers and/or symptomatic thyroid disorders appeared more often in LKM1-positive patients (50% vs 3%, P < .0001). Both female sex and LKM1 positivity were predictors of AITD, but only the latter remained significant after logistic regression analysis. Cross-reactivity to all 7 linear epitopes encoding homologous amino acid sequences shared by the HCV polyprotein, CYP2D6 (the LKM1 autoantigen), and thyroperoxidase was detected in 86% LKM1-positive HCV patients with clinical thyroid disorders, but in none of the LKM1-positive or negative HCV patients without thyroid disease, and none of an HCV-negative control group comprising subjects with LKM1-positive autoimmune hepatitis or AITD without liver disease ( P < .0001). Patients receiving interferon therapy for hepatitis C seropositive for LKM1 are susceptible to develop AITDs, in association with treatment. Molecular mimicry and epitope spreading are potential pathogenic mechanisms.

Hashimoto's thyroiditis and acute chest syndrome revealing sickle cell anemia in a 32 years female patient.

PubMed

Igala, Marielle; Nsame, Daniela; Ova, Jennie Dorothée Guelongo Okouango; Cherkaoui, Siham; Oukkach, Bouchra; Quessar, Asmae

2015-01-01

Sickle cell anemia results from a single amino acid substitution in the gene encoding the β-globin subunit. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. Hashimoto's thyroiditis is a common thyroid disease now recognized as an auto-immune thyroid disorder, it is usually thought to be haemolytic autoimmune anemia. We report the case of a 32 years old women admitted for chest pain and haemolysis anemia in which Hashimoto's thyroiditis and sickle cell anemia were found. In our observation the patient is a young woman whose examination did not show signs of goitre but the analysis of thyroid function tests performed before an auto-immune hemolytic anemia (confirmed by a high level of unconjugated bilirubin and a Coombs test positive for IgG) has found thyroid stimulating hormone (TSH) and positive thyroid antibody at rates in excess of 4.5 times their normal value. In the same period, as the hemolytic anemia, and before the atypical chest pain and anguish they generated in the patient, the search for hemoglobinopathies was made despite the absence of a family history of haematological disease or painful attacks in childhood. Patient electrophoresis's led to research similar cases in the family. The mother was the first to be analyzed with ultimately diagnosed with sickle cell trait have previously been ignored. This case would be a form with few symptoms because the patient does not describe painful crises in childhood or adolescence.

Hyperthyroidism in an infant of a mother with autoimmune hypothyroidism with positive TSH receptor antibodies.

PubMed

Joshi, Kriti; Zacharin, Margaret

2018-04-25

Neonatal hyperthyroidism is rare, seen in infants of mothers with Graves' disease (GD), with transplacental transfer of thyroid-stimulating hormone receptor (TSHR) antibodies (TRAbs). We describe a neonate with severe hyperthyroidism due to TRAbs, born to a mother with autoimmune hypothyroidism. A baby boy born preterm at 35 weeks had irritability, tachycardia and proptosis after birth. The mother had autoimmune hypothyroidism, from age 10, with thyroxine replacement and normal thyroid function throughout her pregnancy. She had never been thyrotoxic. There was a family history of Hashimoto's thyroiditis (HT) and GD. The baby's thyroid function on day 3 demonstrated gross thyrotoxicosis, TSH<0.01 mIU/L (normal range [NR]<10 mIU/L), free thyroxine (FT4)>77 pmol/L (20-35), free triiodothyronine (FT3) 15.4 pmol/L (4.2-8.3) and TRAb 18.4 IU/L (<1.8). The mother's TRAb was 24.7 IU/L. Thyrotoxicosis required propranolol and carbimazole (CBZ). Thyroid function normalized within 10 days. The baby was weaned off medication by 7 weeks. He remains euthyroid. We postulate that this mother had co-existing destructive thyroiditis and thyroid-stimulating antibodies (TSAbs) and TSHR blocking antibodies (TBAb), rendering her unable to raise a thyrotoxic response to the TSAbs but with predominant TSAb transmission to her infant. Maternal history of any thyroid disorder may increase the risk of transmission to an infant, requiring a careful clinical assessment of the neonate, with important implications for future pregnancies.

[Triggering role of emotional stress and childbirth. Unexpected occurrence of Graves' disease compared to 96 cases of Hashimoto thyroiditis and 97 cases of thyroid nodules].

PubMed

Martin-du Pan, R C

1998-07-01

98 patients with Graves' disease have been compared to 95 patients with Hashimoto's thyroiditis and to 97 patients with benign thyroid nodules (control group) in order to evaluate the triggering role of major stressors and pregnancy in the occurrence of autoimmune thyroid diseases. A stress factor has been encountered in 11% cases of Graves' disease and in 6% of Hashimoto's and thyroid nodes (chi 2 test, not different). Graves' disease occurred after a pregnancy in 25% of the women in child bearing age versus 10% of the cases of Hashimoto's (p < 0.05) and 13% of the thyroid nodes. The role of stressors, if any, in triggering Graves' disease seems to be weak and dubious compared to the role of pregnancy and post-partum. It is assumed that the decrease of immunosuppressive hormones occurring after stress or delivery could induce a rebound autoimmune reaction responsible for the thyroid disease. In Hashimoto's thyroiditis, stress and pregnancies do not seem to have any triggering role.

Hypokalemic Paralysis: A Hidden Card of Several Autoimmune Diseases

PubMed Central

Velarde-Mejía, Yelitza; Gamboa-Cárdenas, Rocío; Ugarte-Gil, Manuel; Asurza, César Pastor

2017-01-01

Acute hypokalemic paralysis is a rare and potentially fatal condition, with few related causes, one of which highlights distal renal tubular acidosis (dRTA). Distal renal tubular acidosis is a rare complication of several autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome, and Hashimoto thyroiditis. We report a case of a lupic patient who presented rapidly progressive quadriparesis in the context of active renal disease. Research revealed severe refractory hypokalemia, metabolic acidosis, and alkaline urine suggestive of dRTA. We diagnosed Sjögren’s syndrome based on sicca symptoms, an abnormal salivary glands’ nuclear scan and the presence of anti-Ro/SSA and anti-La/SSB. In addition, the finding of thyroid peroxidase, thyroglobulin antibodies, and hypothyroidism led us to the diagnosis of Hashimoto thyroiditis. Due to the active renal involvement on the context of systemic lupus erythematosus and Sjögren’s syndrome, the patient received immunosuppression with rituximab, resulting in a progressive and complete improvement. PMID:28839447

Thyroid disturbance related to chronic hepatitis C infection: role of CXCL10.

PubMed

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Barros, Raffaelle K; Marui, Suemi

2013-01-01

Association between autoimmune thyroid diseases (AITD) and hepatitis C is controversial, but may occur or worsen during alpha-interferon treatment. The mechanism responsible for autoimmune diseases in infected patients has not been fully elucidated. This study aims to evaluate the frequency of AITD in chronic hepatitis C and the association of chemokine (CXC motif) ligand 10 (CXCL10) and AITD. One hundred and three patients with chronic hepatitis C and 96 controls were prospectively selected to clinical, hormonal, thyroid autoimmunity and ultrasound exams, besides thyroxine-binding globulin (TBG) and CXCL10 measurements and hepatic biopsies. The frequency of AITD among infected subjects was similar to controls. TT3 and TT4 distributions were right shifted, as was TBG, which correlated to both of them. Thyroid heterogeneity and hypoechogenicity were associated with AITD. Increased vascularization was more prevalent in chronic hepatitis C.CXCL10 was higher in infected patients (p=0.007) but was not related to thyroid dysfunction. Increase in CXCL10 levels were consistent with hepatic necroinflammatory activity (p=0.011). In summary, no association was found between chronic hepatitis C and AITD. Infected subjects had higher TT3 and TT4 which were correlated to TBG. Increased CXCL10 was not associated to thyroid dysfunction in HCV-infected population.

Interaction of interferon alpha therapy with thyroid function tests in the management of hepatitis C: a case report.

PubMed

Gill, Gurmit; Bajwa, Hammad; Strouhal, Peter; Buch, Harit N

2016-09-15

Interferon alpha is a widely used therapeutic agent in the treatment of hepatitis C virus infection. Clinical thyroid disease is seen in nearly 15 % of patients receiving interferon alpha for hepatitis C virus infection. The mechanism of thyroid dysfunction with interferon alpha is either autoimmune or inflammatory. We report a case of young woman who developed biphasic thyroid dysfunction posing a diagnostic challenge, while receiving interferon alpha treatment for hepatitis C virus infection. A 29-year-old, Caucasian woman with type 1 diabetes and hepatitis C virus infection was referred with hyperthyroidism, while she was at 17 weeks of a planned 24-week course of interferon alpha therapy. A laboratory investigation revealed a thyroid stimulation hormone level of 0.005 mU/L (0.350-4.94), free thyroxine of 45.6 pmol/L (9.0-19.0) and free tri-iodothyronine of 12.6 pmol/L (2.6-5.7). She had a mild neutropenia and alanine aminotransferase at double the reference value. Her thyroid peroxidase antibody level was 497 ku/L (<5.6) and thyroid inhibitory factor 7 IU/L (>1.8 iu/l is positive). Thyroid scintigraphy with technetium99 scan confirmed a normal-sized thyroid gland with diffuse but normal overall uptake. A diagnosis of interferon alpha-triggered autoimmune hyperthyroidism as opposed to an inflammatory thyroiditis was made. She was offered radioactive iodine therapy, as thionamides were considered inappropriate in view of her liver disease and mild neutropenia. Due to our patient's personal circumstances, radioactive iodine therapy was delayed by 8 weeks and her thyrotoxic symptoms were controlled with beta-blockers alone. A repeat thyroid function test, 4 weeks post treatment with interferon alpha, indicated spontaneous conversion to hypothyroidism with a thyroid stimulation hormone level of 100 mU/L, free thyroxine of 5.2 pmol/L and free tri-iodothyronine of 1.7 pmol/L. She subsequently received levothyroxine for 4 months only and had remained euthyroid for the last 3 months without any treatment. Initial investigations favored the autoimmune nature of hyperthyroidism but follow-up of the case, interestingly, was more consistent with inflammatory thyroiditis. We propose that this can be explained either on the basis of autoimmune subacute thyroiditis or a change in the nature of thyroid stimulation hormone receptor antibody production from stimulating-type to blocking-type antibodies, with disappearance of the latter on discontinuation of interferon alpha.

[Multifactorial analysis of effects of mothers' autoimmune thyroid disease on their infants' intellectual development].

PubMed

Zhu, Hong; Zhao, Zheng-yan; Jiang, You-jun; Liang, Li; Wang, Ji-yue; Mao, Hua-qing; Zou, Chao-chun; Chen, Li-qin; Qu, Yi-ping

2005-05-01

To analyze factors relevant to retarded intellectual development in infants born to mothers with autoimmune disease of thyroid. All the term newborns born to mothers with autoimmune thyroid disease (selection criteria) without asphyxia in all county, city, and provincial hospitals in Zhejiang province (except for Ningbo City) from July 2001 to June 2003 were enrolled through Zhejiang provincial neonatal disease screening network system. The control group was consisted of the neonates who were born to mothers without thyroid disease in these hospitals during the same period. Heel capillary blood samples were collected from the neonates older than 3 days in local hospitals and sent to the center of Zhejiang provincial neonatal disease screening network system. TSH levels were measured by Time Difference Fluorescent Analysis Device (1420 II type, EGG Company, US). If the level of TSH was higher than 9 mU/L, their mothers were called back to the center with their infants within 3 days. If the level of TSH was normal, they were called back to hospitals at age of 28 - 35 days of infants. The pattern of maternal thyroid disease, duration, thyroid function, the history of maternal drug administration, maternal age, gestational age and body weight of the neonates were recorded. The neonatal and maternal serum thyroid function tests were re-performed and the serum TPOAb, TGAb, TRAb and TSAb levels in both neonates and their mothers were measured as well. A 1-year follow-up study was done and all these subjects were investigated by means of Gesell development schedules by special investigators at the age of 1, 3, 6 and 12 months. The results were expressed as developmental quotient. Case-sectional study was performed. Statistical analyses were conducted using SPSS software. The multiple logistic regression analysis was used to analyze factors which might have effect on infantile personal-social ability, adaptive ability, gross motor ability or the fine-motor ability. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons and Dunnet's C test was used when variances were not equal. Correlation analysis was used to compare the anti-thyroid antibody between neonates and their mothers. Poor personal-social ability, adaptive ability, gross motor ability and fine motor ability of infants born to mothers with autoimmune thyroid diseases were found as compared to the infants born to healthy mothers (P < 0.01). Moreover, the infants born to mothers with Hashimoto's thyroiditis had significantly poorer fine motor ability and adaptive ability than those born to mothers with Grave's disease (P < 0.05). The Spearman correlation coefficients of TPOAb, TGAb, TRAb and TSAb were 0.636, 0.574, 0.619 and 0.473, respectively, and all the P values were lower than 0.01.The multifactor logistic regression analysis showed that infantile TPOAb levels and maternal TRAb levels were associated with infantile personal-social ability, adaptive ability, and gross motor; while maternal TPOAb levels and thyroid function during gestation were associated with infantile fine-motor ability (P < 0.05). Maternal autoimmune thyroid diseases during pregnancy had adverse effects on intellectual development of infants. The maternal levels of TPOAb, TRAb and thyroid status were associated with the infantile personal-social ability, adaptive ability, gross motor and fine motor development. In order to reduce the effect on infant, it is necessary to treat adequately the maternal autoimmune thyroid diseases during pregnancy.

[Autoimmune thyroiditis and thyroid cancer].

PubMed

Krátký, Jan; Jiskra, Jan

2015-10-01

Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence.

Thyrotoxicosis in patients with hypothyroidism is not just overtreatment.

PubMed

Kempegowda, Punith; Nayak, Ananth U

2017-07-14

A 62-year-old Caucasian woman presented with hypothyroid symptoms and biochemical thyrotoxic picture. Previously, she underwent right-sided subtotal thyroidectomy and left partial thyroid lobectomy for thyroid lumps, and treated with thyroxine replacement for hypothyroidism. Although there were no significant findings on clinical examination, investigations confirmed thyrotoxicosis with positive autoimmunity against thyroid glandâ€"all in line with a diagnosis of Graves’ hyperthyroidism. We would like to highlight atypical presentations of thyroid dysfunction and conversion of underactive to overactive thyroid status with this case. Early recognition, diagnosis and intervention are essential to prevent and/or reduce associated morbidity and mortality. When encountered with such clinical conundrums, we recommend seeking opinion from an experienced endocrinologist while interpreting such situation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evidence for a primary autoimmune type of diabetes mellitus.

PubMed

Bottazzo, G F; Cudworth, A G; Moul, D J; Doniach, D; Festenstein, H

1978-11-04

Sixty-eight patients with longstanding diabetes and persistent islet-cell antibody and 35 with coexistent diabetes and Graves's disease or primary myxoedema were studied with particular reference to the HLA system and autoantibody patterns. A higher incidence of HLA-B8 than normal was observed in the two groups. An additive relative risk exists when type I diabetes and autoimmune thyroid disease coexist, indicating that different HLA-linked genes may confer susceptibility to the pancreatic and thyroid disorders. Other characteristics, including female predominance, a later onset of diabetes, and a strong family history of autoimmune endocrinopathy, provide further evidence that this form of diabetes is aetiologically distinct from that generally seen in children. These results support the hypothesis of a primary autoimmune type of diabetes mellitus.

Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease.

PubMed

Chen, Fabian; Day, Sara L; Metcalfe, Russell A; Sethi, Gulshan; Kapembwa, Moses S; Brook, M Gary; Churchill, Duncan; de Ruiter, Annemiek; Robinson, Stephen; Lacey, Charles J; Weetman, Anthony P

2005-03-01

Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies. Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.

Autoimmune Thyroiditis and Myasthenia Gravis

PubMed Central

Lopomo, Angela; Berrih-Aknin, Sonia

2017-01-01

Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed. PMID:28751878

Comorbid autoimmune diseases in patients with sarcoidosis: A nationwide case-control study in Taiwan.

PubMed

Wu, Chi-Hung; Chung, Pei-I; Wu, Chen-Yi; Chen, Yen-Ta; Chiu, Yun-Wen; Chang, Yun-Ting; Liu, Han-Nan

2017-04-01

The association between sarcoidosis and autoimmune comorbidities has been reported, however, it has seldom been confirmed by a large nationwide study. Our study aimed to clarify the association between sarcoidosis and autoimmune comorbidities in the Taiwanese. A total of 1237 patients with sarcoidosis and 4948 age- and sex-matched control subjects were selected from the National Health Insurance Research Database of Taiwan from 1997 to 2010. Multiple logistic regressions were performed to calculate the odds of comorbidities between the two groups. The prevalence of sarcoidosis was 2.17/100 000 individuals in Taiwan. Sarcoidosis patients tended to run a higher risk of autoimmune comorbidities than the control group (17.6% vs 9.4%, P < 0.05). Autoimmune thyroid disease (adjusted odd ratio [aOR], 1.32; 95% confidence interval [CI], 1.05-1.64), Sjögren's syndrome (aOR, 11.6; 95% CI, 4.36-31.0) and ankylosing spondylitis (aOR, 3.80; 95% CI, 2.42-5.97) were significantly associated with sarcoidosis. The sex-stratified analyses were carried out to demonstrate a significant association of sarcoidosis with ankylosing spondylitis in both sexes, but with autoimmune thyroid disease in male patients and with Sjögren's syndrome female patients, respectively. Besides, the diagnosis of the autoimmune comorbidities strongly associated with sarcoidosis tended to be established after that of sarcoidosis. This study demonstrated that patients with sarcoidosis tended to have autoimmune thyroid disease, Sjögren's syndrome and ankylosing spondylitis, and the diagnosis of sarcoidosis usually preceded that of associated comorbidities. Clinicians should be alert to autoimmune comorbidities in patients with sarcoidosis. © 2016 Japanese Dermatological Association.

Transient Non-Autoimmune Hyperthyroidism of Early Pregnancy

PubMed Central

Goldman, Alexander M.; Mestman, Jorge H.

2011-01-01

It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications. PMID:21785688

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

Thyroid disorders and the prevalence of antithyroid antibodies in Shiraz population.

PubMed

Karimi, Fariba; Kalantarhormozi, Mohammad Reza; Dabbaghmanesh, Mohammad Hossein; Ranjbar Omrani, Gholamhossein

2014-05-01

Thyroid dysfunction is a common health problem affecting millions of patients worldwide. Autoimmune thyroid disorders are among the most common autoimmune disorders. In this population-based study, we assessed the prevalence of abnormal thyroid function, antithyroid antibodies and the probable relationship between them in Shiraz, southern Iran. Serum thyrotropin (TSH) was determined in 981 subjects (66.8% female and 33.2% male; mean age: 39.1 ± 14.3 years), who were selected with stratified random sampling. Because of the preponderance of females over males, we performed the statistical analyses using sex-weighted data (50% for each sex). Also, antithyroid peroxidase antibodies (TPOAb), and antithyroglobulin antibodies (TgAb) were measured in two random subgroups of 376 and 537 patients respectively). Thyromegaly detected on physical examination. In this cross-sectional study, 8.1% of participants had elevated serum TSH level and 3.4% had low serum TSH level. A statistically significant relationship was found between gender and thyromegaly and TSH values. Positive TPOAb and positive TgAb were detected in 17% and 5.1% of participants respectively. In addition, a significant relationship was observed between elevated TSH levels and positive results for both antibodies. Detectable levels of thyroid antibodies correlated with female sex, while no correlation was observed between detectable levels of thyroid antibodies and thyromegaly. Thyroid disorders, especially elevated TSH level, are common. It seems that autoimmune mechanisms are strongly involved in the etiology of hypothyroidism in this area.

Tick-borne diseases and autoimmunity: A comprehensive review.

PubMed

Rodríguez, Yhojan; Rojas, Manuel; Gershwin, M Eric; Anaya, Juan-Manuel

2018-03-01

Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation. Epidemiological setting (e.g., endemic areas, seasons) and an accurate diagnostic approach (i.e., clinical history, physical examination and laboratory tests) are necessary to confirm TBDs. Further, control and prevention of TBDs is warranted. Research in the fields of ticks microbiome and vaccination (i.e., wildlife and humans) are ahead to control vector transmission and bacterial infection. This review offers a comprehensive update on TBDs and their relationship with autoimmunity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells.

PubMed

Hammerstad, Sara Salehi; Stefan, Mihaela; Blackard, Jason; Owen, Randall P; Lee, Hanna J; Concepcion, Erlinda; Yi, Zhengzi; Zhang, Weijia; Tomer, Yaron

2017-02-01

Thyroiditis is one of the most common extrahepatic manifestations of hepatitis C virus (HCV) infection. By binding to surface cell receptor CD81, HCV envelope glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals. Human thyroid cell lines ML-1 and human thyrocytes in primary cell culture were treated with HCV recombinant E2 protein. The expression of major proinflammatory cytokines was measured at the messenger RNA and protein levels. Next-generation transcriptome analysis was used to identify early changes in gene expression in thyroid cells induced by E2. HCV envelope protein E2 induced strong inflammatory responses in human thyrocytes, resulting in production of interleukin (IL)-8, IL-6, and tumor necrosis factor-α. Furthermore, the E2 protein induced production of several heat shock proteins including HSP60, HSP70p12A, and HSP10, in human primary thyrocytes. In thyroid cell line ML-1, RNA sequencing identified upregulation of molecules involved in innate immune pathways with high levels of proinflammatory cytokines and chemokines and increased expression of costimulatory molecules, specifically CD40, known to be a major thyroid autoimmunity gene. Our data support a key role for HCV envelope protein E2 in triggering thyroid autoimmunity through activation of cytokine pathways by bystander mechanisms. Copyright © 2017 by the Endocrine Society

Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-Ak NOD mice

PubMed Central

Pelletier, Adam-Nicolas; Aliesky, Holly A.; Banuelos, Bianca; Chabot-Roy, Geneviève; Rapoport, Basil; Lesage, Sylvie; McLachlan, Sandra M

2015-01-01

NOD.H2k and NOD.H2h4 mice carry the MHC class II molecule I-Ak associated with susceptibility to experimentally-induced thyroiditis. Dietary iodine enhanced spontaneous thyroid autoimmunity, well known in NOD.H2h4 mice, has not been investigated in NOD.H2k mice. We compared NOD.H2h4 and NOD.H2k strains for thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) without or with dietary sodium iodide (NaI) for up to 32 weeks. TgAb levels were significantly higher in NOD.H2h4 than NOD.H2k mice on NaI and TPOAb developed in NOD.H2h4 but not NOD.H2k mice. DNA exome analysis revealed, in addition to the differences in the chromosome (Chr) 17 MHC regions, that NOD.H2k and particularly NOD.H2h4 mice have substantial non-MHC parental DNA. KEGG pathway-analysis highlighted thyroid autoimmunity and immune-response genes on Chr 17 but not on Chr 7 and 15 parental B10.A4R DNA. Studies of parental strains provided no evidence for non-MHC gene contributions. The exon 10 thyroglobulin haplotype, associated with experimentally-induced thyroiditis, is absent in NOD.H2h4 and NOD.H2k mice and is not a marker for spontaneous murine thyroid autoimmunity. In conclusion, the absence of I-E is a likely explanation for the difference between NOD.H2h4 and NOD.H2k mice in TgAb levels and, as in humans, autoantibody spreading to TPO. PMID:25811933

Longitudinal evaluation of thyroid autoimmunity and function in pregnant Korean women.

PubMed

Han, Seong-Min; Han, Jeong Hee; Park, Jina A; Quinn, Frank A; Park, Joonseok; Oh, Eunsuk

2013-12-01

Maternal thyroid dysfunction during pregnancy has been associated with adverse outcomes for both the mother and child. For this reason, it is important to understand thyroid status in pregnant women. However, there are relatively few published studies that examine thyroid function tests (TFT) and thyroid autoimmunity in non-Western pregnant women. Serum samples were longitudinally collected throughout pregnancy from 108 Korean women. TFT, thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) testing was performed. The impact of gestational age on TPO-Ab and Tg-Ab levels was evaluated and gestational age-specific reference intervals for TFT were established in antibody negative women. In the first trimester, TPO-Ab and Tg-Ab were positive in 13.9% and 16.7% of women, respectively. For antibody positive women, median autoantibody levels for TPO-Ab and Tg-Ab dropped from first trimester to near term (133.7-10.5 IU/mL, and 162.1-21.9 IU/mL, respectively). Antibody status influenced thyroid stimulating hormone (TSH) during the first trimester, and TSH, free T4 (FT4) and total T4 (TT4) in the early second trimester. Later in gestation, no significant differences in TFT were found based on antibody status. Gestational age-specific reference intervals for TFT were calculated in antibody negative women. Laboratory evidence of autoimmune thyroid disease (AITD) is common in this population of pregnant Korean women. Antibody status influences TFT values in the first and early second trimester. Thyroid autoantibody status and titer change in an individual-specific manner throughout pregnancy. Gestational age-specific reference intervals should be utilized for interpretation of TFT results in pregnant women.

The assessment of thyroid autoantibody levels in euthyroid polycystic ovary syndrome patients.

PubMed

Hepşen, Sema; Karaköse, Melia; Çakal, Erman; Öztekin, Sanem; Ünsal, İlknur; Akhanlı, Pınar; Uçan, Bekir; Özbek, Mustafa

2018-04-27

Thyroid hormone abnormalities are commonly seen in polycystic ovary syndrome (PCOS) and have considerable effects on comorbidities. The association with PCOS and thyroid autoimmunity which lead to thyroid pathologies are not revealed clearly. We targeted to commentate anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) antibody levels and thyroid autoimmunity in PCOS. 184 patients who got the diagnosis of PCOS regard to the revised 2003 Rotterdam criteria were embodied in this study. 106 age-matched female volunteers were included in the control group. Characteristics, biochemical parameters, thyroid hormone and autoantibody levels of groups were investigated. Although; we did not find out a statistically significant difference in TSH and sT4 levels between two groups (p>0.05), anti-TPO and anti-TG antibody levels were determined higher in PCOS group significantly (p<0.001). Anti-TPO Ab and anti-TG Ab positivity prevalence of PCOS patients were significantly higher as against to controls (p<0.001; p=0.01). Not only thyroid hormone levels but also thyroid autoantibody levels should be screened during the investigation of PCOS and the patients with positive results need to be followed up carefully in the long run.

Vitiligo and overt thyroid diseases: A nationwide population-based study in Korea.

PubMed

Bae, Jung Min; Lee, June Hyunkyung; Yun, Jae Seung; Han, Byeol; Han, Tae Young

2017-05-01

Associations between vitiligo and thyroid diseases have been reported repeatedly. We investigated the associations between vitiligo and overt autoimmune thyroid diseases and thyroid cancer using the Korean National Health Insurance claims database. We defined patients with vitiligo as those whose records showed ≥4 physician contacts between 2009 and 2013 in which vitiligo was the principal diagnosis. We also established an age- and sex-matched control group without vitiligo (2 per 1 vitiligo patient). The outcomes of interest were concurrent Graves disease and Hashimoto thyroiditis (the patients were taking relevant thyroid medications) and thyroid cancer. The study enrolled 73,336 vitiligo patients and 146,672 controls. Patients with vitiligo were at increased risks of Graves disease (odds ratio [OR] 2.610 [95% confidence interval {CI} 2.319-02.938]), Hashimoto thyroiditis (OR 1.609 [95% CI 1.437-1.802]), and thyroid cancer (OR 1.127 [95% CI 1.022-1.242]), compared with the controls. The associations were consistently stronger in males and younger patients. Individual clinical information was not available, and the homogeneous population may limit the generalizability of the results. Vitiligo was significantly associated with overt autoimmune thyroid diseases and overt thyroid cancer. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Diffuse thyroid 18F-FDG uptake after R-CHOP therapy predicts favorable outcome in patients with DLBCL.

PubMed

Song, Moo-Kon; Chung, Joo-Seop; Kim, Seong-Jang; Kim, Sang-Soo; Shin, Ho-Jin

2015-06-01

Therapy-induced autoimmunity may mediate the destruction of cancer cells. Previous studies have demonstrated that presence of autoimmune thyroid disorder is associated with favorable outcome in patients with solid cancer. Patients with diffuse large B cell lymphoma (DLBCL) who achieved complete response on positron emission tomography/computed tomography (PET/CT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy were enrolled in this study. The patients with and without diffuse thyroid uptake (DTU) were classified by PET/CT. A total of 270 patients were enrolled in this study. DTU related to autoimmune thyroiditis was present in 61 patients. The median time to DTU detection was 5.7 months (range, 0-21.3 months). High International Prognostic Index (IPI) score (progression-free survival [PFS], p = 0.001; overall survival [OS], p = 0.008), bulky mass ≥10 cm (PFS, p = 0.001; OS, p = 0.001), bone marrow involvement (PFS, p < 0.001; OS, p = 0.001), and DTU after R-CHOP therapy (PFS, p < 0.001; OS, p = 0.001) were significantly associated with PFS and OS. High IPI score (PFS, p = 0.003; OS, p = 0.014), BM involvement (PFS, p = 0.009; OS, p = 0.039), and DTU after R-CHOP therapy (PFS, p = 0.002; OS, p = 0.002) were independently associated with PFS and OS. DTU after R-CHOP therapy independently predicted favorable outcomes in patients with DLBCL.

Autoimmune disorders

MedlinePlus

... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... the thyroid or pancreas Joints Muscles Red blood cells Skin A person may have more than one ...

Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18

PubMed Central

Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christid..., M; Sarri, C; Karadima, G; Petersen, M; Xaidara, A; Kanariou, M; Nicolaidou, P

1999-01-01

A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.


Keywords: ring chromosome 18; chromosome 18 deletion; IDDM; hypothyroidism PMID:10051018

Autoimmune diseases in a Nigerian woman--a case report.

PubMed

Talabi, O A; Owolabi, M O; Osotimehin, B O

2003-12-01

Autoimmune diseases (AD) are conditions in which there is the development of antibodies against self cells/ organs. AD could either be organ-specific or non-organ specific (systemic) in clinical presentation. Commonly reported ADs includes: Myasthenia gravis, Hashimoto thyroiditis, Guillian-Barre syndrome, vitiligo, type 1 diabetes mellitus, Graves diseases, Goodpastures syndrome, pemphigus, rheumatoid arthritis, systemic lupus erythematosis, Addisons disease, multiple sclerosis, pernicious anaemia, autoimmune haemolytic anaemia, chronic active hepatitis, idiopathic thrombocytopenic purpura. There is paucity of locally documented information on the occurrence of AD in same patient in our environment. We therefore report the case of a 66 year old woman who presented at the University College Hospital (UCH), Ibadan, with a spectrum of the AD, Vitiligo, rheumatoid arthritis, myasthenia gravis, impaired glucose tolerance.

Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial.

PubMed

Höfling, Danilo B; Chavantes, Maria Cristina; Juliano, Adriana G; Cerri, Giovanni G; Knobel, Meyer; Yoshimura, Elisabeth M; Chammas, Maria Cristina

2013-05-01

Chronic autoimmune thyroiditis (CAT) is the most common cause of acquired hypothyroidism, which requires lifelong levothyroxine replacement therapy. Currently, no effective therapy is available for CAT. Thus, the objective of this study was to evaluate the efficacy of low-level laser therapy (LLLT) in patients with CAT-induced hypothyroidism by testing thyroid function, thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), and ultrasonographic echogenicity. A randomized, placebo-controlled trial with a 9-month follow-up was conducted from 2006 to 2009. Forty-three patients with a history of levothyroxine therapy for CAT-induced hypothyroidism were randomly assigned to receive either 10 sessions of LLLT (830 nm, output power of 50 mW, and fluence of 707 J/cm(2); L group, n=23) or 10 sessions of a placebo treatment (P group, n=20). The levothyroxine was suspended 30 days after the LLLT or placebo procedures. Thyroid function was estimated by the levothyroxine dose required to achieve normal concentrations of T3, T4, free-T4 (fT4), and thyrotropin after 9 months of postlevothyroxine withdrawal. Autoimmunity was assessed by measuring the TPOAb and TgAb levels. A quantitative computerized echogenicity analysis was performed pre- and 30 days postintervention. The results showed a significant difference in the mean levothyroxine dose required to treat the hypothyroidism between the L group (38.59 ± 20.22 μg/day) and the P group (106.88 ± 22.90 μg/day, P<0.001). Lower TPOAb (P=0.043) and greater echogenicity (P<0.001) were also noted in the L group. No TgAb difference was observed. These findings suggest that LLLT was effective at improving thyroid function, promoting reduced TPOAb-mediated autoimmunity and increasing thyroid echogenicity in patients with CAT hypothyroidism.

Use of the immunomodulative influence of low-level laser radiation in the treatment of an autoimmune thyroiditis

NASA Astrophysics Data System (ADS)

Mikhailov, V. A.; Alexandrova, O. A.; Denisov, I. N.

2000-06-01

Use of LLLT for 42 patients with an autoimmune thyroiditis has shown that the helper function of lymphocytes has decreased, the suppressive activity has increased, the quantity of B-lymphocytes has decreased and the immunoregulative index has been normalized. The effect of LLLT application was active about 4 months in 78 percent of the patients. Soft semiconductor laser was used. The radiation was in the IR range of spectrum, wavelength - 890 nm. The technique included cutaneous irradiation of the thymus projection zones, vascular junction and thyroid gland. The total doze was made 2.42 J/cm2.

Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population.

PubMed

Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

2016-08-01

Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected.

Silent Thyroiditis

PubMed Central

Walker, Peter

1984-01-01

Silent or painless thyroiditis is a frequent cause of transient hyperthyroidism, which is characterized by recent onset of symptoms in a patient with a normal to modestly enlarged and firm thyroid gland. The hallmarks of the disease are the absence of thyroidal pain or tenderness and a markedly reduced radioiodine uptake. Histologically, the gland is characterized by an important lymphocytic infiltration, occasionally to the point of lymphoid follicle formation. However, other indices of an autoimmune cause are usually absent. The disease appears to have a predilection for the postpartum period. Relapses may occur with subsequent pregnancies. Otherwise, the course is usually benign and transient, requiring moderate doses of β-adrenergic blocking agents for symptomatic relief. No pathogenetic factors are known, but the disease may conceivably have an autoimmune basis, particularly in the postpartum patient. PMID:21278944

Interleukin 6 -174(G>C) gene polymorphism is related to celiac disease and autoimmune thyroiditis coincidence in diabetes type 1 children.

PubMed

Myśliwiec, Małgorzata; Myśliwska, Jolanta; Zorena, Katarzyna; Balcerska, Anna; Malinowska, Ewa; Wiśniewski, Piotr

2008-10-01

The aim of the study was to assess the relationship between IL-6 gene polymorphism at -174(G>C) and the coincidence of celiac and autoimmune thyroid diseases with type 1 diabetes mellitus (DM1) in children. 200 children with DM1 aged 13.23+/-3.54 years and 172 healthy controls were analyzed. The IL-6 gene -174(G>C) polymorphism at the promoter region of the gene was analyzed by the PCR-RFLP method. The genotype distribution was significantly different in diabetic children as compared to the healthy controls (p=0.01). In DM1 patients GC heterozygotes were the most common (52.5%), while CC homozygotes accuted for 29% and GG homozygotes only for 18% of cases. In contrast, GG homozygotes were much more frequent among healthy children (31%). Besides, the GG homozygotes were significantly more frequent among diabetic children with celiac disease (p=0.04) in relation to those without autoimmune complications. In children with autoimmune thyroiditis, the distribution of the IL-6 genotypes was similar to that seen in diabetic patients without autoimmune complications (p=0.24). The results of our study suggest that the diabetic children, who have IL-6 gene -174GG genotype may have an increased risk for celiac disease development.

Thyroid associated orbitopathy

PubMed Central

Verma, Rajesh; Gupta, Mani; Mehta, Vinod Kumar

2013-01-01

Thyroid-associated orbitopathy (TAO) is a self-limiting auto-immune condition usually associated with Grave's disease. It is characterised by ocular pain, eyelid swelling, chemosis, proptosis and keratopathy. As the mechanism for ophthamoplegia and optic neuropathy is the orbital swelling leading to mechanical restriction of ocular muscles and compression of optic nerve, one expects proptosis rather than ptosis in TAO. We describe a case of a young adult woman who presented with acute onset restriction of movement along with partial ptosis and severe diminution of vision in left eye. The MRI of orbit revealed significant swelling of recti along with signal alteration consistent with TAO. The radio-isotope thyroid scan revealed thyroiditis, and thyroid peroxidase (TPO) antibody was significantly high; hence, the diagnosis of Hashimoto thyroiditis was considered. A course of intravenous methylprednisolone followed by oral steroid was administered, which produced marked improvement in vision and extraocular movement. PMID:23737589

Progressive Non-familial Adult onset Cerebellar Degeneration: An Unusual Occurrence with Hashimoto's Thyroiditis.

PubMed

Rao, Raghavendra S; Sheshadri, Shubha; Bhattacharjee, Dipanjan; Patil, Navin; Rao, Karthik

2018-03-13

Progressive non-familial adult onset cerebellar degeneration has been rarely associated with hypothyroidism and is known to be reversible after therapy. We report a case of cerebellar atrophy in a 31 year old female whose detailed evaluation had revealed sub-clinical hypothyroidism secondary to autoimmune thyroiditis with a very high anti-TPO (anti-thyroid peroxidase) antibody levels. MRI (Magnetic Resonanace Imaging) of brain showed diffuse bilateral cerebellar atrophy. She was treated with thyroid hormone supplementation and after one year of follow up, cerebellar signs had disappeared completely with significant reduction in anti-TPO antibody levels. Imaging of the brain post one year of follow-up revealed normal cerebellum. Hence, we opine that thyroid dysfunction should always be kept in mind while evaluating patients presenting with acute onset cerebellar ataxia as it can be easily reversed with thyroid hormone replacement therapy.

The effect of regulatory T-cell depletion on the spectrum of organ-specific autoimmune diseases in nonobese diabetic mice at different ages.

PubMed

Nakahara, Mami; Nagayama, Yuji; Ichikawa, Tatsuki; Yu, Liping; Eisenbarth, George S; Abiru, Norio

2011-09-01

The nonobese diabetic (NOD) mouse spontaneously develops several autoimmune diseases, including type 1 diabetes and to a lesser extent thyroiditis and sialitis. Imbalance between effector T cells (Teffs) and regulatory T cells (Tregs) has recently been proposed as a mechanism for the disease pathogenesis in NOD mice, but previous studies have shown the various outcomes by different timing and methods of Treg-depletion. This study was, therefore, designed to compare the consequences of Treg-depletion by the same method (anti-CD25 antibody) on the spectrum of organ-specific autoimmune diseases in NOD mice of different ages. Treg-depletion by anti-CD25 antibody at 10 days of age accelerated development of all three diseases we examined (insulitis/diabetes, thyroiditis, and sialitis); Treg-depletion at 4 weeks of age accelerated only diabetes but not thyroiditis or sialitis; and Treg-depletion at 12 weeks of age hastened only development of thyroiditis and exhibited little influence on diabetes or sialitis. Increased levels of insulin autoantibodies (IAA) were, however, observed in mice depleted of Tregs at 10 days of age, not in those at 4 weeks. Thus, the consequences of Treg-depletion on the spectrum of organ-specific autoimmune diseases depend on the timing of anti-CD25 antibody injection in NOD mice. Aging gradually tips balance between Teffs and Tregs toward Teff-dominance for diabetes, but this balance for thyroiditis and sialitis likely alters more intricately. Our data also suggest that the levels of IAA are not necessarily correlated with diabetes development.

Graves' disease in 2.5 years old girl - 6-years-long observation.

PubMed

Jonak, Olimpia; Połubok, Joanna; Barg, Ewa

2016-01-01

Pediatric Graves' disease is rare in young children, more frequent in children with other autoimmune diseases or with family history of autoimmune thyroid disease. The 2.5 year old girl was admitted to the hospital with tachycardia and subfebrile temperature. The girl presented symptoms of atopic dermatitis. Child's mother was diagnosed with Hashimoto disease two months after the child's diagnosis. In physical examination of the child, enlarged thyroid was found. At the admission, the laboratory tests revealed decreased TSH (0.001 uIU/ml), increased both FT3 (>30 pg/ml) and FT4 (3.43 ng/dl), but normal levels of anti-thyreoglobulin antibodies (ATG - 0.64 IU/ml) and anti-thyroid peroxidase antibodies (ATPO - 0 IU/ml); thyrotropin receptor antibodies (TRAb) were not identified. The Graves' disease was diagnosed. The girl started treatment with methimazole (2x5mg) and propranolol (due to tachycardia, 2x5mg). The thyroid function (TSH, FT4 and FT3) normalized 1 year after diagnosis and hormone levels remained within normal reference values, but she received methimazole for 18 months. At presen, the patient is 8 years old. She is not receiving any treatment and her thyroid function is correct. The girl still presents symptoms of atopy. In case of symptoms of tachycardia in children, the hyperthyroidism should be taken into consideration. Numerous methods of treatment provide a therapy appropriate to the age and condition of patients. Long remission after treatment with antithyroid drugs could also be achieved in younger (prepubertal) children. © Polish Society for Pediatric Endocrinology and Diabetology.

The End-Diastolic Velocity of Thyroid Arteries Is Strongly Correlated with the Peak Systolic Velocity and Gland Volume in Patients with Autoimmune Thyroiditis

PubMed Central

Marui, Suemi; Buchpiguel, Carlos Alberto; Cerri, Giovanni Guido; Chammas, Maria Cristina

2017-01-01

Background The end-diastolic velocity (EDV) of thyroid arteries reflects peripheral blood flow resistance. Objective The aim was to evaluate EDV correlations with other Doppler sonography parameters and with clinical and biochemical variables in a sample of patients with hypothyroidism caused by chronic autoimmune thyroiditis (CAT). Methods A sample of 48 CAT hypothyroid patients receiving treatment with stable doses of levothyroxine was selected. The participants underwent clinical evaluation and measurement of serum thyrotropin (TSH), total triiodothyronine (T3), total thyroxine (T4), free T4, thyroid peroxidase antibodies (anti-TPO), and antithyroglobulin antibodies (anti-Tg) and Doppler sonography. Results The EDV of the inferior thyroid arteries (ITA-EDV) was strongly and positively correlated with the peak systolic velocity of the inferior thyroid arteries (ITA-PSV, r = 0.919), thyroid volume (r = 0.711), and thyroid visual vascularization pattern (TVP, r = 0.687). There was no correlation between ITA-EDV and the clinical variables, hormones, anti-TPO, or anti-Tg. Conclusion The strong correlation of ITA-EDV with ITA-PSV, TVP, and volume suggests that increased vascularization in CAT may be associated with a reduction in thyroid blood flow resistance, possibly due to an angiogenesis-induced increase in the total vascular cross-sectional area of the parenchyma. PMID:29062583

Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism.

PubMed

Correia, Miguel Fragata; Maria, Ana Teresa; Prado, Sara; Limbert, Catarina

2015-03-06

Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1-5% of infants born to women with Graves' disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis. 2015 BMJ Publishing Group Ltd.

Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism

PubMed Central

Correia, Miguel Fragata; Maria, Ana Teresa; Prado, Sara; Limbert, Catarina

2015-01-01

Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1–5% of infants born to women with Graves’ disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis. PMID:25750228

The relationship between procalcitonin and thyroid autoantibodies in patients with autoimmune thyroiditis.

PubMed

Oncul, Ali; Ates, Ihsan; Arikan, Mehmet Fettah; Yilmaz, Nisbet; Topcuoglu, Canan; Yilmaz, Fatma Meric; Altay, Mustafa

2017-11-01

The aim of this study is to investigate the serum levels of procalcitonin and its association with autoantibodies in patients with euthyroid Hashimoto's thyroiditis. A total of 80 participants were included in the study; 40 of which were newly diagnosed with Hashimoto's thyroiditis, aged over 18, and 40 of which were healthy volunteers. The serum levels of procalcitonin were measured by enzyme-linked immunosorbent assay kit. Thyroid function tests were analyzed in hormone laboratory with Electro-chemiluminescence immunoassay. Hashimoto's thyroiditis patients had higher median procalcitonin levels than those of the control group (34.3 pg/mL vs 27.8 pg/mL respectively; P=.037). Also, male patients had higher median procalcitonin levels as compared to female patients (37 pg/mL vs 27 pg/mL respectively; P=.013). In the Hashimoto's thyroiditis group, procalcitonin level was positively correlated with anti-thyroglobulin and anti-thyroid peroxidase levels (r=.559, P<.001; r=634, P<.001, respectively). The procalcitonin and anti-thyroid peroxidase levels were identified to be an independent predictor in diagnosis of Hashimoto's thyroiditis. The fact that procalcitonin was found to be correlated with thyroid autoantibodies and found to be an independent risk factor for Hashimoto's thyroiditis in the regression analysis in the framework of this study urges us to think that procalcitonin may be associated with the autoimmunity. © 2017 Wiley Periodicals, Inc.

Hypothyroidism

MedlinePlus

... National Agricultural Library website at www. nutrition. gov. Dietary Supplements Iodine is an essential mineral for the thyroid. However, people with autoimmune thyroid disease may be sensitive to harmful side effects from iodine. Taking iodine drops or ...

Foetal and neonatal thyroid disorders.

PubMed

Radetti, G; Zavallone, A; Gentili, L; Beck-Peccoz, P; Bona, G

2002-10-01

Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes recently identified are represented by TSH receptor mutations leading to constitutively activated TSH receptor. Infants born to mothers with Graves' history may develop neonatal thyrotoxicosis. Foetal/neonatal disease is due to transplacental thyrotrophin receptor stimulating antibodies (TRAb) passage. It's extremely important recognizing and treating Graves' disease in mothers as soon as possible, because a thyrotoxic state may have adverse effects on the outcome of pregnancy and both on the foetus and newborn. Thyrotoxic foetuses may develop goitre, tachycardia, hydrops associated with heart failure, growth retardation, craniosynostosis, increased foetal motility and accelerated bone maturation. Neonatal Graves' disease tends to resolve spontaneously within 3-12 weeks as maternal thyroid stimulating immunoglobulins are cleared from the circulation but subsequent development may be impaired by perceptual motor difficulties. Hashimoto's thyroiditis is a very common autoimmune thyroid disease. In presence of maternal Hashimoto's thyroiditis, there are usually no consequences on foetal thyroid, even if antiTPO and antiTg antibodies can be found in the newborn due to transplacental passage. However there are some literature reports describing foetal and neonatal hyperthyroidism in the affected mothers' offspring.

Hyperthyroidism

PubMed Central

Sharma, Mala; Aronow, Wilbert S.; Patel, Laxesh; Gandhi, Kaushang; Desai, Harit

2011-01-01

Summary Hyperthyroidism is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormone. The most common cause of this syndrome is Graves’ disease, followed by toxic multinodular goitre, and solitary hyperfunctioning nodules. Autoimmune postpartum and subacute thyroiditis, tumors that secrete thyrotropin, and drug-induced thyroid dysfunction, are also important causes. PMID:21455118

Regulatory T Cells in the Control of Autoimmunity: the Essential Role of  Transforming Growth Factor β and Interleukin 4 in the Prevention of Autoimmune Thyroiditis in Rats by Peripheral CD4+CD45RC− Cells and CD4+CD8− Thymocytes

PubMed Central

Seddon, Benedict; Mason, Don

1999-01-01

Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1u rats can be prevented by their reconstitution with peripheral CD4+CD45RC−TCR-α/β+RT6+ cells and CD4+CD8− thymocytes from normal syngeneic donors. These data provide evidence for the role of regulatory T cells in the prevention of a tissue-specific autoimmune disease but the mode of action of these cells has not been reported previously. In this study, autoimmune thyroiditis was induced in PVG.RT1c rats using a similar protocol of thymectomy and irradiation. Although a cell-mediated mechanism has been implicated in the pathogenesis of diabetes in PVG.RT1u rats, development of thyroiditis is independent of CD8+ T cells and is characterized by high titers of immunoglobulin (Ig)G1 antithyroglobulin antibodies, indicating a major humoral component in the pathogenesis of disease. As with autoimmune diabetes in PVG.RT1u rats, development of thyroiditis was prevented by the transfer of CD4+CD45RC− and CD4+CD8− thymocytes from normal donors but not by CD4+CD45RC+ peripheral T cells. We now show that transforming growth factor (TGF)-β and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. The prevention of both diabetes and thyroiditis by CD4+CD45RC− peripheral cells and CD4+CD8− thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-β and IL-4. The observation that the same two cytokines were implicated in the protective mechanism, whether thymocytes or peripheral cells were used to prevent autoimmunity, strongly suggests that the regulatory cells from both sources act in the same way and that the thymocytes are programmed in the periphery for their protective role. The implications of this result with respect to immunological homeostasis are discussed. PMID:9892610

Asymmetric chorea as presenting symptom in Graves' disease.

PubMed

Park, Jinsung; Kim, Jung-Guk; Park, Sung-Pa; Lee, Ho-Won

2012-04-01

Chorea is an involuntary movement disorder characterized by irregular, brief movements that flow from one body part to another in a non-stereotyped fashion. In rare instances, chorea is associated with autoimmune thyroid disease. Most of them have been related with Hashimoto's encephalopathy and few cases have been related with Graves' disease. Most reported cases have been in women with Graves' disease. We describe a 16-year-old male patient with asymmetric chorea as presenting symptom in Graves' disease. He had no family history of neurological disease. Brain imaging, laboratory findings and electroencephalogram demonstrated no abnormality except for thyroid dysfunction which was proved by thyroid function test, sonography and radioiodine uptake scan. Asymmetric chorea improved over months after anti-thyroid medications. This asymmetry could be explained by difference in increased hypersensitivity or by the difference in the number of dopamine receptors, and an asymmetrical breakdown of blood-brain barrier due to their genetic differences.

Meta-analysis of the correlation between Helicobacter pylori infection and autoimmune thyroid diseases

PubMed Central

Zhang, Chengfei; Wang, Tieshan; Guo, Xuan; Wu, Lili; Qin, Lingling; Liu, Tonghua

2017-01-01

Objective This study presents a systematic meta-analysis of the correlation between Helicobacter pylori (H. pylori) infection and autoimmune thyroid diseases (AITD). Materials and Methods Fifteen articles including 3,046 cases were selected (1,716 observational and 1,330 control cases). These data were analyzed using Stata12.0 meta-analysis software. Results H. pylori infection was positively correlated with the occurrence of AITD (OR = 2.25, 95% CI: 1.72–2.93). Infection with H. pylori strains positive for the cytotoxin-associated gene A (CagA) were positively correlated with AITD (OR = 1.99, 95% CI: 1.07–3.70). There was no significant difference between infections detected using enzyme-linked immunosorbent assay (ELISA) and other methods (χ2 = 2.151, p = 0.143). Patients with Grave’s disease (GD) and Hashimoto’s thyroiditis (HT) were more susceptible to H. pylori infection (GD: OR = 2.78, 95% CI: 1.68–4.61; HT: OR = 2.16, 95% CI: 1.44–3.23), while the rate of H. pylori infection did not differ between GD and HT (χ2 = 3.113, p = 0.078). Conclusions H. pylori infection correlated with GD and HT, and the eradication of H. pylori infection could reduce thyroid autoantibodies. PMID:29383192

Autoimmune encephalopathy associated with thyroid autoantibodies as the cause of reversible cognitive impairment

PubMed Central

Maroz, Natallia; Bernhardt, Nechama; Chow, Robert Dobbin

2012-01-01

We herewith describe a patient with acute confusion, expressive aphasia and generalized seizures. A through workup excluded most causes of encephalopathy. He was, however, found to have TSH=18.6 MIU/ml, T3reverse=0.44nmol/L, T4=0.8ng/dl and Anti-Thyroid-Peroxidase AB titer >1000 IU/ml. Based on the above findings the patient was diagnosed with Hashimoto's encephalopathy and his mental status showed dramatic improvement (MMS 30/30) with high dose prednisone. Hashimoto's encephalopathy is rare disorder of presumed autoimmune origin characterized by cognitive decline, seizures, neuro-psychiatric symptoms, high titers of Anti-Thyroid-Peroxidase AB, and a positive response to steroids. PMID:23882359

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

PubMed Central

Teumer, Alexander; Brown, Suzanne J.; Jensen, Richard A.; Rawal, Rajesh; Roef, Greet L.; Plantinga, Theo S.; Vermeulen, Sita H.; Lahti, Jari; Simmonds, Matthew J.; Husemoen, Lise Lotte N.; Freathy, Rachel M.; Shields, Beverley M.; Pietzner, Diana; Nagy, Rebecca; Broer, Linda; Chaker, Layal; Korevaar, Tim I. M.; Plia, Maria Grazia; Sala, Cinzia; Völker, Uwe; Richards, J. Brent; Sweep, Fred C.; Gieger, Christian; Corre, Tanguy; Kajantie, Eero; Thuesen, Betina; Taes, Youri E.; Visser, W. Edward; Hattersley, Andrew T.; Kratzsch, Jürgen; Hamilton, Alexander; Li, Wei; Homuth, Georg; Lobina, Monia; Mariotti, Stefano; Soranzo, Nicole; Cocca, Massimiliano; Nauck, Matthias; Spielhagen, Christin; Ross, Alec; Arnold, Alice; van de Bunt, Martijn; Liyanarachchi, Sandya; Heier, Margit; Grabe, Hans Jörgen; Masciullo, Corrado; Galesloot, Tessel E.; Lim, Ee M.; Reischl, Eva; Leedman, Peter J.; Lai, Sandra; Delitala, Alessandro; Bremner, Alexandra P.; Philips, David I. W.; Beilby, John P.; Mulas, Antonella; Vocale, Matteo; Abecasis, Goncalo; Forsen, Tom; James, Alan; Widen, Elisabeth; Hui, Jennie; Prokisch, Holger; Rietzschel, Ernst E.; Palotie, Aarno; Feddema, Peter; Fletcher, Stephen J.; Schramm, Katharina; Rotter, Jerome I.; Kluttig, Alexander; Radke, Dörte; Traglia, Michela; Surdulescu, Gabriela L.; He, Huiling; Franklyn, Jayne A.; Tiller, Daniel; Vaidya, Bijay; de Meyer, Tim; Jørgensen, Torben; Eriksson, Johan G.; O'Leary, Peter C.; Wichmann, Eric; Hermus, Ad R.; Psaty, Bruce M.; Ittermann, Till; Hofman, Albert; Bosi, Emanuele; Schlessinger, David; Wallaschofski, Henri; Pirastu, Nicola; Aulchenko, Yurii S.; de la Chapelle, Albert; Netea-Maier, Romana T.; Gough, Stephen C. L.; Meyer zu Schwabedissen, Henriette; Frayling, Timothy M.; Kaufman, Jean-Marc; Linneberg, Allan; Räikkönen, Katri; Smit, Johannes W. A.; Kiemeney, Lambertus A.; Rivadeneira, Fernando; Uitterlinden, André G.; Walsh, John P.; Meisinger, Christa; den Heijer, Martin; Visser, Theo J.; Spector, Timothy D.; Wilson, Scott G.; Völzke, Henry; Cappola, Anne; Toniolo, Daniela; Sanna, Serena; Naitza, Silvia; Peeters, Robin P.

2014-01-01

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10−8) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10−8), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10−6), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10−4). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10−7 and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10−5). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10−3). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction. PMID:24586183

[Seric 21-hydroxilase antibodies in patients with anti-microsomal fraction antibodies. Autoimmune polyendocrine syndrome].

PubMed

Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel

2007-01-01

Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review

PubMed Central

Xing, Wanjia; Liu, Xiaohong; He, Qingqing; Zhang, Zongjing; Jiang, Zhaoshun

2017-01-01

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAFV600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAFV600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm. PMID:28928829

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review.

PubMed

Xing, Wanjia; Liu, Xiaohong; He, Qingqing; Zhang, Zongjing; Jiang, Zhaoshun

2017-09-01

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAF V600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAF V600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm.

Polymorphisms in the TNFA and IL6 Genes Represent Risk Factors for Autoimmune Thyroid Disease

PubMed Central

Alvelos, Inês; Mendes, Adélia; Santos, Liliana R.; Machado, José Carlos; Melo, Miguel; Esteves, César; Neves, Celestino; Sobrinho-Simões, Manuel; Soares, Paula

2014-01-01

Background Autoimmune thyroid disease (AITD) comprises diseases including Hashimoto's thyroiditis and Graves' disease, both characterized by reactivity to autoantigens causing, respectively, inflammatory destruction and autoimmune stimulation of the thyroid-stimulating hormone receptor. AITD is the most common thyroid disease and the leading form of autoimmune disease in women. Cytokines are key regulators of the immune and inflammatory responses; therefore, genetic variants at cytokine-encoding genes are potential risk factors for AITD. Methods Polymorphisms in the IL6-174 G/C (rs1800795), TNFA-308 G/A (rs1800629), IL1B-511 C/T (rs16944), and IFNGR1-56 T/C (rs2234711) genes were assessed in a case-control study comprising 420 Hashimoto's thyroiditis patients, 111 Graves' disease patients and 735 unrelated controls from Portugal. Genetic variants were discriminated by real-time PCR using TaqMan SNP genotyping assays. Results A significant association was found between the allele A in TNFA-308 G/A and Hashimoto's thyroiditis, both in the dominant (OR = 1.82, CI = 1.37–2.43, p-value = 4.4×10−5) and log-additive (OR = 1.64, CI = 1.28–2.10, p-value = 8.2×10−5) models. The allele C in IL6-174 G/C is also associated with Hashimoto's thyroiditis, however, only retained significance after multiple testing correction in the log-additive model (OR = 1.28, CI = 1.06–1.54, p-value = 8.9×10−3). The group with Graves' disease also registered a higher frequency of the allele A in TNFA-308 G/A compared with controls both in the dominant (OR = 1.85, CI = 1.19–2.87, p-value = 7.0×10−3) and log-additive (OR = 1.69, CI = 1.17–2.44, p-value = 6.6×10−3) models. The risk for Hashimoto's thyroiditis and Graves' disease increases with the number of risk alleles (OR for two risk alleles is, respectively, 2.27 and 2.59). Conclusions This study reports significant associations of genetic variants in TNFA and IL6 with the risk for AITD, highlighting the relevance of polymorphisms in inflammation-related genes in the etiopathogenesis of AITD. PMID:25127106

Nivolumab-induced thyroid dysfunction in patients with lung cancer.

PubMed

Ramos-Levi, Ana M; Rogado, Jacobo; Sanchez-Torres, Jose Miguel; Colomer, Ramón; Marazuela, Mónica

2018-06-14

Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab. Potential risk factors are analyzed, and strategies for IRAE management are proposed. Forty consecutive patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) were studied, paying particular attention to development of endocrine IRAEs (thyroid, hypophyseal, adrenal, or pancreatic) and clinical outcome. Thyroid function changes were found in 9 patients (22.5%), of which six developed hypothyroidism and three had hyperthyroidism after a median of 3.8 and 2.3 cycles of nivolumab respectively. Only one patient had thyroid-related symptoms. Thyroid autoimmunity was negative in all cases. Hyperthyroid patients showed no uptake in iodine scintigraphy, and their hormone values returned to normal in less than six months. Nivolumab was discontinued for toxicity in one patient. One patient with hyperthyroidism also developed autoimmune diabetes, and one patient with hypothyroidism also had hypogonadism. After a median follow-up of 7.6 months, 25 patients (62.5%) showed response to nivolumab. Univariate and multivariate analyses showed no differences between patients who developed thyroid changes and those who did not. Thyroid changes after treatment with nivolumab are common and warrant active laboratory monitoring. The underlying mechanisms and their relevance deserve further research. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents.

PubMed

Krzewska, Aleksandra; Ben-Skowronek, Iwona

2016-01-01

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome). The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests.

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

PubMed

Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi

2017-02-06

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

Diagnostic value of antithyroid peroxidase antibody for incidental autoimmune thyroiditis based on histopathologic results.

PubMed

Rho, Myung Ho; Kim, Dong Wook; Hong, Hyun Pyo; Park, Young Mi; Kwon, Min Jeong; Jung, Soo Jin; Kim, Young Wook; Kang, Taewoo

2012-12-01

Detection of antithyroid peroxidase antibody (TPOAb) is widely used in the diagnosis of autoimmune thyroiditis (AIT), but no research has evaluated the diagnostic accuracy of TPOAb detection using histopathologic reference standards. To fill this research gap, this study assessed the diagnostic accuracy of detection of TPOAb and that of other serological markers in asymptomatic patients who had been diagnosed with AIT by histopathologic analysis after thyroid surgery. After review of patient records, 598 patients who had undergone thyroid nodule surgery were enrolled for examination for thyroid parenchyma by a pathologist and classification into no co-existing lymphocytic thyroiditis, Hashimoto thyroiditis, or non-Hashimoto type of lymphocytic thyroiditis (NHLT). The correlation between patient serological data and thyroid parenchyma pathology was analyzed. Statistically significant differences (P < 0.05) were found between co-existing lymphocytic thyroiditis and no co-existing lymphocytic thyroiditis groups regarding thyroid-stimulating hormone (TSH) and TPOAb levels. And, TPOAb titer was significantly associated with the degree of inflammation. An abnormal TPOAb titer was found in 86 of the 598 patients (14.4 %) and the specificity of TPOAb detection for AIT diagnosis was found to be 96.9 %. The prevalence of Hashimoto thyroiditis and NHLT in the 560 papillary thyroid cancer (PTC) patients was found to be 7.9 and 17.9 %, respectively. The results indicate that TPOAb titer is associated with the degree of thyroid inflammation and that detection of TPOAb is a very specific means of diagnosing AIT. The results also indicate that the incidence of AIT and PTC coexistence is relatively high.

Association of type 1 diabetes with two Loci on 12q13 and 16p13 and the influence coexisting thyroid autoimmunity in Japanese.

PubMed

Awata, Takuya; Kawasaki, Eiji; Tanaka, Shoichiro; Ikegami, Hiroshi; Maruyama, Taro; Shimada, Akira; Nakanishi, Koji; Kobayashi, Tetsuro; Iizuka, Hiroyuki; Uga, Miho; Kawabata, Yumiko; Kanazawa, Yasuhiko; Kurihara, Susumu; Osaki, Masataka; Katayama, Shigehiro

2009-01-01

Recent genome-wide association studies have identified several novel type 1 diabetes (T1D) loci in white populations. In line with recent findings, we conducted a replication study of two loci on chromosome 12p13 and 16p13 and assessed their potential associations with thyroid autoimmunity in a Japanese population. Two single-nucleotide polymorphisms (SNPs), rs2292399 in ERBB3 on 12q13 and rs2903692 in CLEC16A (or KIAA0350) on 16p13, were analyzed in Japanese subjects consisting of 735 T1D patients, 330 patients with autoimmune thyroid disease (AITD), and 621 control subjects. According to a case-control study and logistic regression adjusting for sex and age, we observed that these SNPs in ERBB3 and CLEC16A were both significantly associated with T1D, with the risk alleles being consistent with those in white populations [adjusting odds ratio by multiplicative model: 1.37 (1.13-1.67), P = 0.001; and 1.28 (1.02-1.60), P = 0.030, respectively]. In both SNPs, the association was suggested to be stronger in T1D complicated with AITD (Graves' disease, Hashimoto's thyroiditis, or thyroid autoantibodies). Furthermore, a joint analysis, with the INS and CTLA4 SNPs, revealed that CTLA4 rs3087243, ERBB3 rs2292399, and CLEC16A rs2903692, but not INS rs689, were significant risk factors for the cooccurrence of AITD in Japanese T1D. We confirmed two loci on 12q13 and 16p13 that were identified by the independent genome-wide association studies in white populations, thus suggesting that these loci contribute to T1D susceptibility across different ethnic groups. In addition, these loci may also be associated with the cooccurrence of thyroid autoimmunity in T1D.

Influence of cigarette smoking on thyroid gland--an update.

PubMed

Sawicka-Gutaj, Nadia; Gutaj, Paweł; Sowiński, Jerzy; Wender-Ożegowska, Ewa; Czarnywojtek, Agata; Brązert, Jacek; Ruchała, Marek

2014-01-01

Many studies have shown that cigarette smoking exerts multiple effects on the thyroid gland. Smoking seems to induce changes in thyroid function tests, like decrease in TSH and increase in thyroid hormones. However, these alterations are usually mild. In addition, tobacco smoking may also play a role in thyroid autoimmunity. Many studies have confirmed a significant influence of smoking on Graves' hyperthyroidism and particularly on Graves' orbitopathy. Here, smoking may increase the risk of disease development, may reduce the effectiveness of treatment, and eventually induce relapse. The role of smoking in Hashimoto's thyroiditis is not as well established as in Graves' disease. Nonetheless, lower prevalence of thyroglobulin antibodies, thyroperoxidase antibodies and hypothyroidism were found in smokers. These findings contrast with a study that reported increased risk of hypothyroidism in smokers with Hashimoto's thyroiditis. Moreover, cigarette smoking increases the incidence of multinodular goitre, especially in iodine-deficient areas. Some studies have examined cigarette smoking in relation to the risk of thyroid cancer. Interestingly, many of them have shown that smoking may reduce the risk of differentiated thyroid cancer. Furthermore, both active and passive smoking during pregnancy might modify maternal and foetal thyroid function. This review evaluates the current data concerning the influence of cigarette smoking on thyroid gland, including hormonal changes, autoimmunity and selected diseases. These findings, however, in our opinion, should be carefully evaluated and some of them are not totally evidence-based. Further studies are required to explain the effects of smoking upon thyroid pathophysiology.

Technetium-99m thyroid scan; does it have a diagnostic aid in sub-clinical auto-immune thyroid disease in systemic lupus erythematosus patients?

PubMed

Amin, A; Alkemary, A; Abdo, M; Salama, M

2016-02-01

Technetium-99m (Tc-99m) thyroid scintigraphy is a well known diagnostic tool that shows the entire gland in a single image. We aimed to evaluate its additive diagnostic value in subclinical autoimmune thyroid disease (S-AITD) in systemic lupus erythematosus (SLE) patients. We investigated 100 systemic lupus erythematosus (SLE) patients without overt thyroid involvement (eight men and 92 women; mean age 40±6.5 years) and 50 age and sex matched controls. All were subjected to thyroid evaluation using anti-thyroglobulin (anti-TG) and anti-thyroid peroxidase (anti-TPO) antibodies; hormones (FT3; FT4 and TSH) and Tc-99m thyroid scintigraphy. 14/100 (14%) and none (0%) were positive for S-AITD in SLE and control groups, respectively (P = 0.0001). They were classified by thyroid scintigraphy and hormonal profile into 2/14 Hashimoto; 10/14 atrophic thyroiditis and 2/14 Graves' disease. Anti-TPO was elevated in 12 SLE cases, while anti-TG was elevated in only 2/14 (P = 0.0001). Thyroid scintigraphy showed statistically significant associations with FT4, TSH and anti-TPO. Tc-99m thyroid scintigraphy may have an additional diagnostic role in S-AITD among SLE patients, with an impact on patient management. This potential needs to be further evaluated in a larger series on a multicenter basis. © The Author(s) 2015.

Non cancer thyroid and other endocrine disease in children and adults exposed to ionizing radiation after the ChNPP accident.

PubMed

Kaminskyi, O V; Kopylova, O V; Afanasyev, D E; Pronin, O V

2015-12-01

To summarize the verified clinical and epidemiological data on the natural history of non cancer endocrine disease in remote period after the ChNPP accident in survivors of adult and children age. Retrospective estimation was carried out of data on 24,588 adult persons and 20,087 chil dren survived after the ChNNP accident and being healthy or having any diseases. Data were retrieved from database of the Clinical Epidemiological Registry (CER), NRCRM for the 23 years (1992-2014) of survey. Average total external radiation dose in adults was 0.187 Gy, range of thyroid dose in children was 0.1-1.55 Gy. These data were verifies in a separate clinical study. Anthropometric, laboratory biochemical and hormonal assay values, thyroid ultrasound imaging patterns and radiation dose values were retrieved for the study. Retrospective data review for the 1992-2014 period indicated that incidence of thyroid disease in all per sons survived after the ChNPP accident run at 40.29% with 35.37% among the clean up workers, 27.24% among evac uees, and 28.6% among population of contaminated territories that all is significantly (p < 0.0001) higher vs. the entire population of Ukraine (3.9%). Following non cancer endocrine diseases were most prevalent in the ChNPP acci dent survivors: nodular goiter (14.35%), chronic autoimmune thyroiditis (~8%), pre obesity and obesity (41.9% and 36.8% respectively), prediabetes and diabetes mellitus (15.5% and 21.4% respectively). Nodular goiter (21.8%), chronic autoimmune thyroiditis (12.95%), pre obesity and obesity (41.71% and 33.61% respectively), and predia betes and diabetes mellitus (8.6% and 12.15% respectively) were most often diagnosed in the ChNPP accident clean up workers. Children evacuated from the 30 kilometer exclusion zone were a critical population group. They were diagnosed diffuse non toxic goiter in 43.68%, chronic autoimmune thyroiditis in 1.74%, primary hypothyroidism in 0.96%, and nodular goiter in 2.57%. Peak prevalence of chronic autoimmune thyroiditis occurred in 2001-2003 i.e. in a period of their intensive pubertal maturation. In children (first generation) of exposed parents the thyroid dis ease was revealed in 42.64%, that exceeded the incidence in control group, chronic autoimmune thyroiditis was found rarer i.e. in 0.45%, diffuse non toxic goiter in 9.5-13.8%, nodular goiter in 1.7%. Non cancer endocrine disease in children and adults exposed to ionizing radiation is frequent and reg istered in 3 53% of persons. It occurs in most of survivors 10-15 years upon the impact of radiation factor as a result of man made accident and continues to grow slowly in 30 years. O. V. Kaminskyi, O. V. Kopylova, D. E. Afanasyev, O. V. Pronin.

Autoimmunity and autoimmune co-morbidities in psoriasis.

PubMed

Furue, Kazuhisa; Ito, Takamichi; Tsuji, Gaku; Kadono, Takafumi; Nakahara, Takeshi; Furue, Masutaka

2018-05-01

Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the tumour necrosis factor-α/interleukin-23/interleukin-17 axis is now known to be the major mechanism in the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is co-morbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune co-morbidities in psoriasis. © 2018 John Wiley & Sons Ltd.

Relationship Among Pulmonary Hypertension, Autoimmunity, Thyroid Hormones and Dyspnea in Patients With Hyperthyroidism.

PubMed

Zuhur, Sayid Shafi; Baykiz, Derya; Kara, Sonat Pinar; Sahin, Ertan; Kuzu, Idris; Elbuken, Gulsah

2017-04-01

Previous studies have reported conflicting results regarding the mechanisms underlying the pathophysiology of pulmonary hypertension (PHT) in patients with hyperthyroidism. Therefore, in this study, we investigated the association between PHT and thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3, fT4 and dyspnea during daily activities in a large population of patients with hyperthyroidism. A total of 129 consecutive patients with hyperthyroidism, 37 with hypothyroidism and 38 euthyroid controls were enrolled in this study. The modified medical research council scale was used for the assessment of dyspnea in daily activities. All the patients and euthyroid controls underwent transthoracic echocardiography for the assessment of PHT. Mild PHT was present in 35%, 36%, 13.5% and 5% of the patients with Graves׳ disease, toxic multinodular goiter, hypothyroidism and euthyroid controls, respectively. Pulmonary vascular resistance (PVR) was higher in hyperthyroid patients with PHT than in those without PHT. Moreover, a significant positive correlation was found between modified medical research council scale and pulmonary artery systolic pressure as well as PVR in patients with hyperthyroidism. No association was found between PHT and serum TSH receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3 and fT4 levels. Mild PHT is present in a significant proportion of patients with hyperthyroidism, regardless of etiology. PVR appears to be the main cause of PHT in patients with hyperthyroidism, and neither autoimmunity nor thyroid hormones are associated with PHT in these patients. Mild dyspnea during daily activities in patients with hyperthyroidism may be related to PHT; however, severe dyspnea requires further evaluation. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Graves' disease following subacute thyroiditis.

PubMed

Nakano, Yoshishige; Kurihara, Hideo; Sasaki, Jun

2011-12-01

Subacute thyroiditis is a painful, inflammatory disease frequently accompanied with fever. It is suspected to be a viral infectious disease, while Graves' disease is an autoimmune disease. Thus, there appears to be no etiological relationship between the two diseases. A total of 25,267 thyroid disease patients made their first visits to our thyroid clinic during a period of 24 years between 1985 and 2008. Among them, subacute thyroiditis and Graves' disease accounted for 918 patients (3.6%) and 4,617 patients (18.2%), respectively. We have encountered 7 patients (one male and six female) with subacute thyroiditis followed by Graves' disease in this period (0.15% of the 4,617 patients with Graves' disease and 0.76% of the 918 patients with subacute thyroiditis). The age ranges were 40~66 years (mean 48.7 years) at the onset of subacute thyroiditis. The intervals between the onsets of subacute thyroiditis and Graves' disease were 1~8 months (mean 4.7 months). Because Graves' disease was preceded by subacute thyroiditis, the signs and symptoms of both diseases were evident together in the intervening period. The diagnosis of Graves' disease in those patients is always difficult because of atypical signs and symptoms and an unclear onset time. The causes of the Graves'disease that followed subacute thyroiditis are still unknown. However, the inflammatory nature of subacute thyroiditis may lead to the activation of the autoimmune response in susceptible subjects, resulting in the onset of Graves' disease. Graves' disease should be suspected when a high blood level of thyroid hormone persists after subacute thyroiditis.

Type of fish consumed and thyroid autoimmunity in pregnancy and postpartum.

PubMed

Benvenga, Salvatore; Vigo, Maria Teresa; Metro, Daniela; Granese, Roberta; Vita, Roberto; Le Donne, Maria

2016-04-01

Fish consumption or supplementation with omega-3 fatty acids was reported to cure and/or prevent autoimmune and nonautoimmune disorders. Serum positivity for thyroid autoantibodies is a predictive marker of postpartum thyroiditis and postpartum depression. We hypothesized that stable consumption of the omega-3-rich oily fish was associated with a more favorable profile of serum thyroid antibodies throughout pregnancy and early postpartum compared with stable consumption of swordfish, a predator that concentrates pollutants. We prospectively measured serum thyroglobulin antibodies and thyroperoxidase antibodies in pregnancy (first, second trimesters) and postpartum (day 4), in 236 thyroid disease-free, nonsmoker Caucasian women with stable dietary habits. We did not measure thyroid autoantibodies prior to pregnancy. Women were divided into groups A (n = 48; swordfish), B (n = 52; oily fish), C (n = 68; swordfish + other fish, not necessarily oily fish), and D (n = 68; fish other than swordfish and oily fish). Major endpoints were positivity rates and serum concentrations of the two autoantibodies. We resorted to previous studies for the estimated content of fatty acids and microelements in the consumed fish. Positivity rates and serum concentrations of both antibodies were the greatest in group A and the lowest in group B (P < 0.001 and P < 0.05 to < 0.001, respectively). Relationship between monthly fish consumption and serum concentrations of either antibody was direct in group A but inverse in group B. The estimated content of omega-3 fatty acids in fish consumed by group B was the greatest (P < 0.001 vs. any other group). These data reinforce recommendations that pregnant women should avoid consuming swordfish and indicate consumption of oily fish as a favorable alternative. Because thyroid autoantibodies are markers of autoimmune-related postpartum problems, our data suggest a dietary prophylaxis of such problems.

Thyroid Dysfunction in Primary Biliary Cholangitis: A Comparative Study at Two European Centers.

PubMed

Floreani, Annarosa; Mangini, Chiara; Reig, Anna; Franceschet, Irene; Cazzagon, Nora; Perini, Lisa; Caballería, Llorenç; Cocchio, Silvia; Baldo, Vincenzo; Parés, Albert

2017-01-01

Primary biliary cholangitis (PBC) is often associated with other autoimmune diseases, but little is known about the influence of thyroid disease (TD) on the natural history of PBC. Our aim is to analyze the association between PBC and TD, and the latter's impact on the natural history of PBC at two European centers. The study involved 921 PBC patients enrolled between 1975 and 2015 in Padova (376 patients) and Barcelona (545 patients), with a mean follow-up of 126.9±91.7 months. Data were recorded on patients' histological stage at diagnosis, biochemical data, associated extrahepatic autoimmune conditions, and clinical events, including hepatic decompensation. A total of 150 patients (16.3%) had TD, including 94 patients (10.2%) with Hashimoto's thyroiditis; 15 (1.6%) with Graves' disease; 22 (2.4%) with multinodular goiter; 7 (0.8%) with thyroid cancer; and 12 (1.3%) with other thyroid conditions. The prevalence of different types of TD was similar in Padova and Barcelona, except for Graves' disease and thyroid cancer, which were more frequent in the Padova cohort (15.7 vs. 5.0%, and 8.6 vs. 1.3%, respectively, P<0.05). Overall, there were no differences between PBC patients with and without TD in terms of their histological stage at diagnosis, hepatic decompensation events, occurrence of HCC, or liver transplantation rate. The presence of associated TD was not associated with lower survival for PBC patients in either cohort. TDs, and autoimmune TD like Hashimoto's thyroiditis in particular, are often associated with PBC, but the presence of TD does not influence the rate of hepatic complications or the natural history of PBC.

Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer.

PubMed

Yu, Hea Min; Park, Soon Hyun; Lee, Jae Min; Park, Kang Seo

2013-09-01

Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Purpura fulminans and anticardiolipin antibodies in a patient with Grave's disease.

PubMed

Ligier, Sophie; Pham, Cuong D; Watters, A Kevin; Kassis, Jeannine; Fortin, Paul R

2002-01-01

We describe a patient with Grave's discase who developed purpura fulminans and who was found to have anticardiolipin antibodies after being started on propylthiouracil (PTU). We discuss the potential role of the antiphospholipid antibody in this woman's presentation, and its association to both PTU and autoimmune thyroid disease.

Early thyroxine treatment in Down syndrome and thyroid function later in life.

PubMed

Zwaveling-Soonawala, Nitash; Witteveen, M Emma; Marchal, Jan Pieter; Klouwer, Femke C C; Ikelaar, Nadine A; Smets, Anne M J B; van Rijn, Rick R; Endert, Erik; Fliers, Eric; van Trotsenburg, A S Paul

2017-05-01

The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis. We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis. TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L; P  = 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) ( P  = 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower ( P  < 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group. Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia. © 2017 European Society of Endocrinology.

[Prevalence of non-thyroid autoantibodies in autoimmune dysthyroidies].

PubMed

Guerin, V; Prestat, F; Bene, M C; Faure, G; Hartemann, P; Leclere, J

1989-01-01

Organ- and non organ-specific autoantibodies can be detected in patients with AITD but large comparative studies have seldom been performed. This study evaluated the prevalence of anti-thyroid, -smooth muscle, -mitochondria, -parietal gastric cells, -salivary duct, -nuclear and -ds DNA autoantibodies assayed by indirect immunofluorescence in 224 patients with Graves' disease or Hashimoto's thyroiditis. Results evidenced a high prevalence of antinuclear antibodies, mostly of non homogenous fluorescence in Graves' (63.1%) and Hashimoto's patients (65.5%), as well as for antisalivary duct antibodies (55.2 and 75%). No positive anti-ds DNA were noticed. No correlation was found between antithyroid antibodies and the others. Different hypothesis could explain this observation which favours a general dysregulation of the autoimmune system.

Bipolar disorder and antithyroid antibodies: review and case series.

PubMed

Bocchetta, Alberto; Traccis, Francesco; Mosca, Enrica; Serra, Alessandra; Tamburini, Giorgio; Loviselli, Andrea

2016-12-01

Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms.

Association between FokI, ApaI and TaqI RFLP polymorphisms in VDR gene and Hashimoto's thyroiditis: preliminary data from female patients in Serbia.

PubMed

Djurovic, J; Stojkovic, O; Ozdemir, O; Silan, F; Akurut, C; Todorovic, J; Savic, K; Stamenkovic, G

2015-06-01

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disorder caused by an interaction between genes and environmental triggers. Intrathyroid lymphocytic infiltration may lead to progressive destruction of thyroid tissue and consequently to hypothyroidism. Many studies in different populations have shown association between vitamin D receptor (VDR) gene polymorphisms and various autoimmune diseases, including HT. The study included 44 female patients (mean age ± standard deviation 38 ± 5.4) with Hashimoto's thyroiditis and 32 healthy age-matched, sex-matched and geographically matched controls without personal history of autoimmune and endocrine diseases. Genomic DNA was isolated from peripheral blood-EDTA, and the target VDR gene was genotyped by PCR-RFLP technique after VDR-FokI (rs2228570), VDR-ApaI (rs7975232) and VDR-TaqI (rs731236) restriction enzymes digestion. We used spss 20.0 integrated software for data analysis and found a significant difference in the genotype distribution of VDR-FokI polymorphism between patients with HT and controls (P = 0.009). For ApaI and TaqI, we observed a higher frequency of variant allele in patients with HT, which was not significantly different compared to control women (P > 0.05). The current first and preliminary results identified the association between VDR-FokI gene polymorphism and Hashimoto's thyroiditis in Serbian population. Results need to be supported by further investigations that define haplotype patterns for VDR gene polymorphisms in a larger group of HT patients of both sexes. © 2015 John Wiley & Sons Ltd.

Causes of appearance of scintigraphic hot areas on thyroid scintigraphy analyzed with clinical features and comparative ultrasonographic findings.

PubMed

Iwata, Masahiro; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Fujita, Toru; Konishi, Junji

2002-06-01

This study was done retrospectively to analyze the ultrasonographic (US) findings in thyroid scintigraphic hot areas (HA). Three-thousand, eight-hundred and thirty-nine consecutive patients who underwent 99mTc-pertechnetate (n = 3435) or 123I (n = 457) scintigraphy were analyzed. HA were regarded as present when the tracer concentration was greater than the remaining thyroid tissue, or when hemilobar uptake was observed. High-resolution US examinations were performed with a real-time electronic linear scanner with a 7.5 or 10 MHz transducer. One hundred and four (2.7%) were found to be scintigraphic HA (n = 120). US revealed a nodular lesion or well-demarcated thyroid tissue corresponding to the HA in 94 areas (78.4%, Category 1), an ill-defined region with different echogenicity in 13 areas (10.8%, Category 2), and no correlating lesion in 13 areas (10.8%, Category 3). These 104 patients included 43 with adenomatous goiter (59 areas), 33 with adenoma, 11 with Hashimoto's thyroiditis, 5 with primary thyroid cancer, 4 with euthyroid ophthalmic Graves' disease (EOG), 3 with hemilobar atrophy or hypogenesis, 2 with hemilobar agenesis, 2 with hypothyroidism with blocking-type TSH-receptor antibodies (TSHRAb), I with acute suppurative thyroiditis. Among the 59 adenomatous nodules and 33 adenomas, 51 (86.4%) and 32 (97.0%), respectively, belonged to Category 1. A solitary toxic nodule was significantly larger and occurs more often in older patients than in younger patients. On the other hand, all 17 patients with known autoimmune thyroid diseases including Hashimoto's thyroiditis, EOG and hypothyroidism with blocking TSHRAb belonged to Category 2 or 3. Possible underlying mechanisms are 1) hyperfunctioning tumors or nodules, 2) localized functioning thyroid tissue freed from autoimmune destruction, inflammation or tumor invasion, 3) congenital abnormality, 4) clusters of hyperactive follicular cells caused by long-term TSH and/or TSHRAb stimulation, 5) asymmetry, etc. Scintigraphic HA are observed in patients with various thyroid diseases and high-resolution US appears to be helpful clinically for the differential diagnosis of the above mentioned disorders.

Recurrent pregnancy loss in patients with thyroid dysfunction.

PubMed

Sarkar, Debanjali

2012-12-01

Thyroid disturbances are common in women during their reproductive years. Thyroid dysfunction interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. This review highlights the gap in knowledge regarding the contribution of thyroid dysfunction in reproduction. Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. It is estimated that approximately 8-12% of all pregnancy losses are the result of endocrine factors. Autoimmune thyroid disease is present in around 4% of young females and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum, on the other hand. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences. Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality, and miscarriage. Universal screening for thyroid hormone abnormalities is not routinely recommended at present, but thyroid function must be examined in female with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.

[Functional tear production indices in thyroid eye disease].

PubMed

Safonova, T N; Likhvantseva, V G; Gontiurova, O A; Rudenko, E I; Vygodin, V A

2013-01-01

Analysis of functional tear production indices in patients with Grave's disease and thyroid eye disease confirmed lacrimal gland involvement in inflammatory autoimmune process. Close direct correlation was found between tear production and main disease characteristics - severity and activity.

Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

PubMed

Zaveljcina, Janez; Legan, Mateja; Gaberšček, Simona

2016-05-01

We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension.

The possible role of CD4⁺CD25(high)Foxp3⁺/CD4⁺IL-17A⁺ cell imbalance in the autoimmunity of patients with Hashimoto thyroiditis.

PubMed

Xue, Haibo; Yu, Xiurong; Ma, Lei; Song, Shoujun; Li, Yuanbin; Zhang, Li; Yang, Tingting; Liu, Huan

2015-12-01

Hashimoto thyroiditis (HT) is a prototypic organ-specific autoimmune thyroid disease, for which the exact etiology remains unclear. The aim of this study was to investigate dynamic changes in regulatory T cell (Treg) and T helper 17 cell (Th17) populations in patients with HT at different stages of thyroid dysfunction, as well as to analyze the possible correlation between the Treg/Th17 cell axis and autoimmune status in HT. We assessed thyroid function and autoantibody serology both in HT patients and in healthy controls (HCs) and divided HT patients into three subgroups according to thyroid function. We then determined the percentages of Treg and Th17 cells in peripheral blood mononuclear cells and analyzed mRNA expression of the Treg and Th17 cell-defining transcription factors Foxp3 and RORγt. In addition, serum levels of TGF-β and IL-17A were assessed. We found that the percentage of Treg cells, Foxp3 mRNA levels, and the ratio of Treg/Th17 cells were all significantly lower in HT patients, while Th17 cell percentages and RORγt mRNA levels were significantly higher. Interestingly, we also observed significant differences in these measurements between HT patient subgroups. Serum IL-17A levels were markedly increased in HT patients, while serum concentrations of TGF-β were lower, compared to HCs. The ratio of Treg/Th17 cells was negatively correlated with the levels of serum thyroperoxidase antibody, thyroglobulin antibody, and thyrotropin (TSH) in HT patients. Taken together, our data suggest that the balance between Treg and Th17 cells shifts in favor of Th17 cells during clinical progression of HT, which is negatively correlated with levels of thyroid-specific autoantibodies and TSH, implying that Treg/Th17 cell imbalance may contribute to thyroid damage in HT.

Thyroid hormone modulates insulin-like growth factor-I(IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases.

PubMed

Inukai, T; Takanashi, K; Takebayashi, K; Fujiwara, Y; Tayama, K; Takemura, Y

1999-10-01

The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, P<0.001). The levels of both IGF-I and IFGBP-3 were significantly higher in the hyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (P<0.05). Levels of IGFBP-3, but not IGF-I levels, showed a significant positive correlation with the levels of free T4 and free T3. In Graves' disease, levels of TPOAb, but not of TRAb, showed a significant positive correlation with IGFBP-3. We conclude that in patients with autoimmune thyroid diseases, thyroid hormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.

Noonan's Syndrome and Autoimmune Thyroiditis

ERIC Educational Resources Information Center

Vesterhus, Per; Aarskog, Dagfinn

1973-01-01

Thyroid abnormalities were studies in seven boys and three girls, 4- to 17-years-old, with Noonan's syndrome, characterized by mental retardation, ocular anomalies (wide spaced eyes, drooped eye lids, or strabismus), heart lesions, characteristics of Turner's syndrome, and normal karyotypes (chromosome arrangement). (MC)

Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid

PubMed Central

Cho, Byuri Angela; Yoo, Seong-Keun; Song, Young Shin; Kim, Su-jin; Lee, Kyu Eun; Shong, Minho

2018-01-01

Background: Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions. Methods: Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging. Results: The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10−6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10−4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03). Conclusions: Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease. PMID:29652618

Anti-PIT-1 antibody syndrome; a novel clinical entity leading to hypopituitarism.

PubMed

Bando, Hironori; Iguchi, Genzo; Yamamoto, Masaaki; Hidaka-Takeno, Ryoko; Takahashi, Yutaka

2015-03-01

Various hypothalamic-pituitary diseases cause hypopituitarism. Inflammation related to autoimmunity also causes hypopituitarism. Hypophysitis is a representative disease caused by autoimmunity. Generally, anterior pituitary hormones are non-specifically impaired in this condition, but specific hormone defects have been reported in some cases. Anti-PIT-1 (pituitary-specific transcription factor 1) antibody syndrome is a novel clinical entity that presents an acquired combined pituitary hormone deficiency characterized by a specific defect in growth hormone, prolactin, and thyroid-stimulating hormone. Circulating anti-PIT-1 antibody along with various autoantibodies are detected with multiple endocrine organopathy, meeting the definition of autoimmune polyglandular syndrome. Mechanistically, cytotoxic T lymphocytes that specifically react with PIT-1 protein play an important role in the development of this syndrome.

Clinical Significance of Thyrotrophin Binding Inhibitor Immunoglobulins in Patients with Graves’ Disease and Various Types of Thyroiditis

PubMed Central

Lee, Chong Suk; Kim, Doo Man; Kim, Chong Soon; Yoo, Hyung Joon

1987-01-01

It is well known that thyrotrophin receptor antibodies are present in the sera of patients with autoimmune thyroid disease. There is now compelling evidence that the hyperthyroidism of Graves’ disease is due to antibodies to the thyrotrophin (TSH) receptor. The measurement of these antibodies is valuable in the diagnosis and monitoring of Graves’ disease and in predicting the outcome of treatment. In the present study, thyrotrophin binding inhibitor immunoglobulin (TBII) activites were measured by radioreceptor assay, according to the method of Shewring and Smith1), in 30 patients with Graves’ disease, 13 patients with Hashimoto’s thyroiditis, 20 patients with lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH), 5 patients with postpartum thyroiditis, and 7 patients with subacute thyroiditis. The TBII activity results a mean of 3.0±3.0% in normal controls, 44.8±8.7% in Graves’ disease, 8.69±8.06% in Hashimoto’s thyroiditis, 7.63±2.32% in LT-SRH, 3.33±1.16% in postpartum thyroiditis, and 2.67±2.33% in subacute thyroiditis respectively. These clinical and laboratory findings show that TBII also plays a role in the pathogenesis of Graves’ disease. The levels of the TBII activties in Hashimoto’s thyroiditis and LT-SRH, suggest a pathognomic role similar to that of Graves’ disease in above mentioned two disease, but that TBII activity is not significant in postpartum or subacute thyroiditis. PMID:2908728

[Evaluation of salivary gland function in women with autoimmune thyroid diseases].

PubMed

Koczor-Rozmus, Aleksandra; Zwirska-Korczala, Krystyna; Sadlak-Nowicka, Jadwiga; Ilewicz, Leşzek; Mayer-Parka, Danuta; Wierucka-Młynarczyk, Beata

2003-01-01

The function of the salivary glands is regulated by nervous system which influences salivary circulation. Moreover the volume of secreted saliva depends on the humoral agents, including thyroid hormones. The aim of the study was to determine the quantity of the secreted mixed resting and stimulated saliva in women with autoimmune thyroid diseases (AITD) depending on the function of the thyroid gland (hyperthyroidism, hypothyroidism and euthyroidism). The association between thyroid antibody concentrations (TPO-Ab, Tg-Ab, TR-Ab) and volume of secreted saliva was also examined. Studies were performed in 106 women suffering from AITD and 15 healthy volunteers. In hyperthyroid women there was a decrease in volumes of resting (57.14%) and stimulated (89.29%) saliva. Similarly, a decrease in secretion of resting (75%) and stimulated (66.67%) saliva was shown in hypothyroid women. In euthyroid patients with AITD there was a partial normalisation of salivary glands function. The negative correlation between concentrations of TPO-Ab, Tg-Ab and the volume of resting and stimulated saliva was found. In conclusion, AITD may be associated with disturbances in salivary secretion which depends on thyroid hormones production. It can be suggested that autoimmunological processes within salivary glands may influence their function.

Primary Amenorrhea Associated with Hyperprolactinemia in Polyglandular Autoimmune Syndrome Type II: A Case Report.

PubMed

Cottas, Luiza Tizziotti; Borges, Maria de Fátima; Oliveira, Lívia Prata Santos; Resende, Ana Luísa Mantovani; Ataíde, Meire Soares; Resende, Elisabete Aparecida Mantovani Rodrigues

2018-06-27

Polyglandular autoimmune syndrome type II (PGA-II) is a rare immunoendocrinopathy syndrome characterized by the occurrence of autoimmune Addison disease along with diabetes mellitus type 1 and/or autoimmune thyroid disease. Here, we report the case of a 23-year-old female with PGA-II who was followed up at the dermatology and endocrinology clinics of the Universidade Federal do Triângulo Mineiro, located in the state of Minas Gerais, Brazil. First, the patient presented diffuse skin hyperpigmentation, vitiligo; and in sequence, due to vomiting, appetite and weight loss, hypoglycemia, amenorrhea, and galactorrhea, the patient was then diagnosed with PGA-II. The patient also presented intense hyperprolactinemia due to primary hypothyroidism. The late diagnosis of PGA-II is frequent because the disorder is uncommon and has non-specific clinical manifestations. This report emphasizes the significance of a timely diagnosis and appropriate treatment to reduce morbidity and mortality associated with these diseases, especially Addison disease. The present study reports a rare case of a patient with PGA-II with primary amenorrhea associated with hyperprolactinemia. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Unravelling thyroid dysfunction in rheumatoid arthritis: History matters.

PubMed

Anoop, Joseph; Geetha, Francis; Jyothi, Idiculla; Rekha, Pradeep; Shobha, Vineeta

2018-03-01

Autoimmune thyroid disease (AITD) frequently coexists with other systemic autoimmune conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Due to the overlapping and nonspecific nature of symptoms, it is difficult to clinically uncover thyroidal illnesses in RA patients. This study was conducted to estimate the prevalence of thyroid dysfunction including the presence of anti-thyroid peroxidase (antiTPO) autoantibodies in patients with RA and to analyze symptomatology of thyroid dysfunction in patients diagnosed with RA. This cross-sectional, prospective study was conducted on 100 patients with RA, attending the Rheumatology Outpatient Department at St John's Medical College and Hospital, Bangalore, India. Twenty-two patients had biochemical evidence of thyroid dysfunction, hypothyroidism being the commonest (15/22 patients). Although fatigue and hair loss were the most common symptoms, only weight gain and cold intolerance were found to be statistically significant (P < 0.05) predictors of hypothyroidism and 32 patients were antiTPO positive. It was observed that equal numbers of patients developed hypothyroidism after diagnosis of RA and vice versa. History taking at the bedside to elicit symptoms, especially weight gain and cold intolerance, is quintessential to ensure timely diagnosis of hypothyroidism. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

PubMed Central

Rapoport, Basil

2013-01-01

Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.” Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction. Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo. Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves' disease. These changes involve differences in TSAb versus TBAb concentrations, affinities and/or potencies in individual patients. Thus, anti-thyroid drugs or suppression/hemodilution in pregnancy reduce initially low TSAb levels even further, leading to TBAb dominance. In contrast, TSAb emergence after LT4 administration may be sufficient to counteract TBAb inhibition. The occurrence of “switching” emphasizes the need for careful patient monitoring and management. Finally, whole genome screening of relatively rare “switch” patients and appropriate Graves' and Hashimoto's controls could provide unexpected and valuable information regarding the basis for thyroid autoimmunity. PMID:23025526

Seven newly identified loci for autoimmune thyroid disease.

PubMed

Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

2012-12-01

Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

Immunoproteasome Overexpression Underlies the Pathogenesis of Thyroid Oncocytes and Primary Hypothyroidism: Studies in Humans and Mice

PubMed Central

Kimura, Hiroaki J.; Chen, Cindy Y.; Tzou, Shey-Cherng; Rocchi, Roberto; Landek-Salgado, Melissa A.; Suzuki, Koichi; Kimura, Miho; Rose, Noel R.; Caturegli, Patrizio

2009-01-01

Background Oncocytes of the thyroid gland (Hürthle cells) are found in tumors and autoimmune diseases. They have a unique appearance characterized by abundant granular eosinophilic cytoplasm and hyperchromatic nucleus. Their pathogenesis has remained, thus far, unknown. Methodology/Principal Findings Using transgenic mice chronically expressing IFNγ in thyroid gland, we showed changes in the thyroid follicular epithelium reminiscent of the human oncocyte. Transcriptome analysis comparing transgenic to wild type thyrocytes revealed increased levels of immunoproteasome subunits like LMP2 in transgenics, suggesting an important role of the immunoproteasome in oncocyte pathogenesis. Pharmacologic blockade of the proteasome, in fact, ameliorated the oncocytic phenotype. Genetic deletion of LMP2 subunit prevented the development of the oncocytic phenotype and primary hypothyroidism. LMP2 was also found expressed in oncocytes from patients with Hashimoto thyroiditis and Hürthle cell tumors. Conclusions/Significance In summary, we report that oncocytes are the result of an increased immunoproteasome expression secondary to a chronic inflammatory milieu, and suggest LMP2 as a novel therapeutic target for the treatment of oncocytic lesions and autoimmune hypothyroidism. PMID:19924240

CD8+ T cells induce thyroid epithelial cell hyperplasia and fibrosis.

PubMed

Yu, Shiguang; Fang, Yujiang; Sharav, Tumenjargal; Sharp, Gordon C; Braley-Mullen, Helen

2011-02-15

CD8(+) T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8(+) T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ(-/-) NOD.H-2h4 SCID mice in the absence of CD4(+) T cells. Because CD8(+) T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8(+) T cells in autoimmune disease. In contrast to the ability of purified CD8(+) T cells to induce thyrocyte proliferation, CD4(+) T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti-TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ(-/-) splenocytes. This suggests that targeting CD8(+) T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.

Relational Stability of Thyroid Hormones in Euthyroid Subjects and Patients with Autoimmune Thyroid Disease

PubMed Central

Hoermann, Rudolf; Midgley, John E.M.; Larisch, Rolf; Dietrich, Johannes W.

2016-01-01

Background/Aim Operating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range. Methods We analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease. Results In the euthyroid controls, the FT3-FT4 (free triiodothyronine-free thyroxine) ratio was strongly associated with the FT4-TSH ratio (tau = −0.22, p < 0.001, even after correcting for spurious correlation), linking T4 to T3 conversion with TSH-standardized T4 production. Using a homeostatic model, we estimated both global deiodinase activity and maximum thyroid capacity. Both parameters were nonlinearly and inversely associated, trending in opposite directions across the euthyroid reference range. Within the panel of controls, the subgroup with a relatively lower thyroid capacity (<2.5 pmol/s) displayed lower FT4 levels, but maintained FT3 at the same concentrations as patients with higher functional and anatomical capacity. The relationships were preserved when extended to the subclinical range in the diseased sample. Conclusion The euthyroid panel does not follow a homogeneous pattern to produce random variation among thyroid hormones and TSH, but forms a heterogeneous group that progressively displays distinctly different levels of homeostatic control across the euthyroid range. This suggests a concept of relational stability with implications for definition of euthyroidism and disease classification. PMID:27843807

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

PubMed

Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

2017-01-01

Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

[Pathophysiology of Grave's disease (author's transl)].

PubMed

Karsenty, G; Schaison, G

1982-02-27

It has been established that Grave's disease is an autoimmune condition characterized by immunization against TSH receptors. Neither the receptors nor the stimulating immunoglobulins have been identified, but there seems to be two types of antireceptor antibodies: some stimulate the production of hormones or of thyroid stimulating immunoglobulins (TSI) and are responsible for thyrotoxicosis; others stimulate cell proliferation or thyroid growth immunoglobulins (TGI) and account for the diffuse goitre. The mechanism that triggers off autoimmunization is still unknown, but the disease frequently occurs in individuals genetically predisposed, as suggested by the high incidence of some HLA B8 and DR W3 antigens.

Autoimmune thyroid disease with ulcerative colitis.

PubMed

Modebe, O

1986-06-01

Two cases of co-existing thyroid disease and ulcerative colitis are reported. Thyroid disorder preceded ulcerative colitis in each case. The presence of acute colitis delayed and obscured the clinical diagnosis of thyrotoxicosis in one case and the colitis could not be controlled until her thyrotoxicosis was treated. Although the specific factors involved in this relationship are now known, an interplay of immunological factors is most probable.

Association of CTLA-4 gene polymorphisms −318C/T and +49A/G and Hashimoto's thyroidits in Zahedan, Iran

PubMed Central

Narooie-Nejad, Mehrnaz; Taji, Omid; Kordi Tamandani, Dor Mohammad; Kaykhaei, Mahmoud Ali

2017-01-01

Hashimoto's thyroiditis (HT) is a chronic inflammation of the thyroid gland and is known as the most common autoimmune disease. Development of autoimmune destruction of thyroid cells is a multi-step process involving convergence of genetic and environmental factors. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) has an important role in homeostasis and negative regulation of immune responses, and is therefore considered to be a key element in the development of autoimmune diseases. The present study evaluated the association of the CTLA-4 gene polymorphisms 318C/T (rs5742909) and +49A/G (rs231775) with HT in an Iranian population (including 82 patients with HT and 104 healthy controls who were referred for routine premarital blood screenings). Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction technique. No significant differences were observed in genotype and allele frequencies in the single nucleotide polymorphisms (SNPs) between cases and controls. In the cases as well as in the controls, the TT genotype in the −318C/T polymorphism was absent and the predominant genotype was CC, while the predominant genotype for the +49A/G SNP was AA. As only few studies in this field have assessed Iranian and even Middle Eastern populations, additional studies with a higher number of samples are recommended to further assess the impact of −318C/T (rs5742909) and +49A/G (rs231775) polymorphisms of CTLA-4 on HT. PMID:28123718

The continuing importance of thyroid scintigraphy in the era of high-resolution ultrasound.

PubMed

Meller, J; Becker, W

2002-08-01

At the molecular level, the uptake of radioiodine and pertechnetate is proportional to the expression of the thyroidal sodium/iodine symporter (NIS). Qualitative and quantitative scintigraphic evaluation of the thyroid is performed with a gamma camera fitted with an on-line computer system and enables determination of the iodine uptake or the technetium uptake (TCTU) as an iodine clearance equivalent. Despite new molecular genetic insights into congenital hypothyroidism, the iodine-123 or pertechnetate scan remains the most accurate test for the detection of ectopic thyroid tissue. Following the identification of specific mutations of the genes coding for the NIS, thyroid peroxidase and pendrin, the discharge test has lost its role in establishing the diagnosis of inherited dyshormonogenesis, but it is still of value in the assessment of defect severity. In PDS mutations the test can be used to establish the diagnosis of syndromic disease. Quantitative pertechnetate scintigraphy is the most sensitive and specific technique for the diagnosis and quantification of thyroid autonomy. The method has proved to be valuable in risk stratification of spontaneous or iodine-induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy and in the evaluation of therapeutic success after definitive treatment. In iodine deficiency areas the thyroid scan remains indispensable for the functional characterisation of a thyroid nodule and is still a first-line diagnostic procedure in cases of suspected thyroid malignancy. This is especially of importance in patients with Graves' disease, among whom a relatively high prevalence of cancer has been found in cold thyroid nodules. While determination of the TCTU is without any value in the differentiation between autoimmune thyroiditis and Graves' disease in most cases, it is of substantial importance in the differentiation between hyperthyroid autoimmune thyroiditis and Graves' disease.

Is autoimmune thyroid dysfunction a risk factor for gestational diabetes?

PubMed

Pascual Corrales, Eider; Andrada, Patricia; Aubá, María; Ruiz Zambrana, Alvaro; Guillén Grima, Francisco; Salvador, Javier; Escalada, Javier; Galofré, Juan C

2014-01-01

Some recent studies have related autoimmune thyroid dysfunction and gestational diabetes (GD). The common factor for both conditions could be the existence of pro-inflammatory homeostasis. The study objective was therefore to assess whether the presence of antithyroid antibodies is related to the occurrence of GD. Fifty-six pregnant women with serum TSH levels ≥ 2.5 mU/mL during the first trimester were retrospectively studied. Antithyroid antibodies were measured, and an O'Sullivan test was performed. GD was diagnosed based on the criteria of the Spanish Group on Diabetes and Pregnancy. Positive antithyroid antibodies were found in 21 (37.50%) women. GD was diagnosed in 15 patients, 6 of whom (10.71%) had positive antibodies, while 9 (16.07%) had negative antibodies. Data were analyzed using exact logistic regression by LogXact-8 Cytel; no statistically significant differences were found between GD patients with positive and negative autoimmunity (OR = 1.15 [95%CI = 0.28-4.51]; P=1.00). The presence of thyroid autoimmunity in women with TSH above the recommended values at the beginning of pregnancy is not associated to development of GD. However, GD prevalence was higher in these patients as compared to the Spanish general population, suggesting the need for closer monitoring in pregnant women with TSH levels ≥ 2.5 mU/mL. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

PubMed

Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

2018-01-01

During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Immune responses to Epstein-Barr virus in individuals with systemic and organ specific autoimmune disorders.

PubMed

Kannangai, R; Sachithanandham, J; Kandathil, A J; Ebenezer, D L; Danda, D; Vasuki, Z; Thomas, N; Vasan, S K; Sridharan, G

2010-01-01

Autoimmune diseases usually manifest in genetically predisposed individuals following an environmental trigger. There are several viral infections including Epstein-Barr virus (EBV) implicated in the pathogenesis of autoimmune disorders. The aim of this study was to look at the antibody pattern to EBV proteins in the plasma of both systemic and organ specific autoimmune disorders, estimate pro-inflammatory plasma cytokines (IL-8 and TNF-alpha) among these autoimmune patients and compare the observations with those in normal healthy controls. Samples from 44 rheumatoid arthritis patients, 25 Hashimoto's thyroiditis patients, appropriately age and sex matched healthy controls were tested for EBV IgM antibodies by an immunoblot assay and two cytokines (IL-8 and TNF-alpha) by commercial assays. Among the rheumatoid arthritis patients, 23 (52%) were positive for EBNA1 antibody, while 13 (52%) of the Hashimoto's thyroiditis patients and 12 (30%) of the healthy controls showed similar bands. The intensity of the bands was high in the autoimmune patients when compared to the bands seen in control samples. The difference in the EBNA1 reactivity between rheumatoid arthritis patients and controls were significant (P = 0.038). There was a significant difference in the IgM reactivity to VCAp19 protein between patients and controls (P = 0.011). Our study showed an increased EBV activation among the autoimmune patient groups compared to the normal healthy controls. Further studies are required to delineate the association between the aetiology of autoimmune disorders and EBV.

Autoantibodies in chronic hepatitis C: A clinical perspective

PubMed Central

Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo de Lucca

2015-01-01

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus (HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of gluten-related seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon (IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmune disease may be present or may be precipitated by IFN-based HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations. PMID:26052396

Dynamic Thiol/Disulphide Homeostasis in Children and Adolescents with Non-Autoimmune Subclinical Hypothyroidism

PubMed Central

Uçaktürk, Seyit Ahmet; Alışık, Murat; Uğur, Çağatay; Elmaoğulları, Selin; Mengen, Eda; Erel, Özcan

2018-01-01

Objective To evaluate the thiol/disulphide homeostasis in children with non-autoimmune subclinical hypothyroidism (SHT). Subjects and Methods Thiol/disulphide homeosta sis, involving native thiol (SH), disulphide (SS), and total thiol (SS + SH), was evaluated in 60 children and adolescents who were negative for thyroid auto-antibodies (anti-thyroid peroxidase, anti-thyroglobulin) and had a thyroid-stimulating hormone (TSH) value of > 5 mIU/L, and in 40 sex- and age-matched healthy control subjects who were negative for thyroid autoantibodies and had normal TSH levels. Lipid profiles and urine iodine levels were also determined. Results SH (466 ± 32.8 vs. 462 ± 32.1 μmol/L p = 0.59), SH + SS (508 ± 34.0 vs. 506 ± 32.7 μmol/L, p = 0.81), SS (21 ± 5.5 vs. 22 ± 5.8 μmol/L, p = 0.41), SS/SH (4.5 ± 1.2 vs. 4.8 ± 1.3%, p = 0.36), SS/SH + SS (4.1 ± 1.0 vs. 4.3 ± 1.1%, p = 0.36) and SH/SH + SS (91 ± 2.1 vs. 91 ± 2.1%, p = 0.31) levels were similar in children with SHT and control subjects (p > 0.05). There was no difference between total cholesterol, triglyceride, and low-density lipoprotein levels in SHT patients and controls. No difference was detected between the patients with or without iodine deficiency in the SHT group in terms of thiol/disulphide homeostasis parameters. Conclusion The status of dynamic thiol/disulphide homeostasis did not change in children and adolescents with non-autoimmune SHT. Future studies are needed for the evaluation of oxidative stress in patients with long-standing non-autoimmune SHT. PMID:29402856

The seroprevalence of antithyroid peroxidase antibodies in bipolar families and bipolar twins: results from two longitudinal studies.

PubMed

Snijders, G; de Witte, L; Mesman, E; Kemner, S; Vonk, R; Brouwer, R; Nolen, W A; Drexhage, H A; Hillegers, M H J

2017-12-01

Previous studies of our group among bipolar offspring and bipolar twins showed significant higher prevalence's and levels of antithyroid peroxidase antibodies (TPO-Abs) in offspring and co-twins (without a mood disorder) compared to controls, suggesting that TPO-Abs might be considered as vulnerability factor (trait marker) for BD development. Here we elucidate, in the same cohorts, but now after 12- and 6-year follow-up, whether TPO-abs should be considered as a 'trait' marker for BD. The present study aims to investigate whether TPO-Abs (1) are stable over time, (2) are associated with lithium-exposure, (3) share a common genetic background with BD and are related to psychopathology. In bipolar offspring and twins, the prevalence of TPO-Abs is stable over time (r s  = .72 p < .001 resp. r s  = .82, p < .001) and not associated with lithium use. At follow-up, an increased prevalence of TPO-abs was again observed in bipolar offspring (10,4% versus 4%) and higher TPO-abs titers were still present in co-twins of bipolar cases compared to control twins [mean 1.06 IU/ml (SD .82) versus mean .82 IU/ml (SD .67)], although statistical significance was lost. Although our results show a trend toward an increased inherited risk of the co-occurrence of BD and thyroid autoimmunity, large-scale studies can only draw final conclusions. Nationwide epidemiological and GWAS studies reach such numbers and support the view of a possible common (autoimmune) etiology of severe mood disorders and chronic recurrent infections and autoimmunity, including thyroid autoimmunity.

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, J.P.; Izembart, M.; Marliac, V.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with /sup 131/I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after /sup 131/I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

Thyroid Autoimmunity is Associated with Decreased Cytotoxicity T Cells in Women with Repeated Implantation Failure

PubMed Central

Huang, Chunyu; Liang, Peiyan; Diao, Lianghui; Liu, Cuicui; Chen, Xian; Li, Guangui; Chen, Cong; Zeng, Yong

2015-01-01

Thyroid autoimmunity (TAI), which is defined as the presence of autoantibodies against thyroid peroxidase (TPO) and/or thyroglobulin (TG), is related to repeated implantation failure (RIF). It is reported that TAI was involved in reproductive failure not only through leading thyroid function abnormality, but it can also be accompanied with immune imbalance. Therefore, this study was designed to investigate the association of thyroid function, immune status and TAI in women with RIF. Blood samples were drawn from 72 women with RIF to evaluate the prevalence of TAI, the thyroid function, the absolute numbers and percentages of lymphocytes. The prevalence of thyroid function abnormality in RIF women with TAI was not significantly different from that in RIF women without TAI (χ2 = 0.484, p > 0.05). The absolute number and percentage of T cells, T helper (Th) cells, B cells and natural killer (NK) cells were not significantly different in RIF women with TAI compared to those without TAI (all p > 0.05). The percentage of T cytotoxicity (Tc) cells was significantly decreased in RIF women with TAI compared to those without TAI (p < 0.05). Meanwhile, Th/Tc ratio was significantly increased (p < 0.05). These results indicated that the decreased Tc percentage and increased Th/Tc ratio may be another influential factor of adverse pregnancy outcomes in RIF women with TAI. PMID:26308040

HASHIMOTO THYROIDITIS AND VESTIBULAR DYSFUNCTION.

PubMed

Chiarella, Giuseppe; Russo, Diego; Monzani, Fabio; Petrolo, Claudio; Fattori, Bruno; Pasqualetti, Giuseppe; Cassandro, Ettore; Costante, Giuseppe

2017-07-01

The aim of this review was to analyze the existing literature concerning the relationship between Hashimoto thyroiditis (HT) and vestibular dysfunction. We used electronic databases (PubMed, EMBASE, Cochrane Library) to search and collect all published articles about the association between HT and vestibular disorders. Several observational and retrospective studies have postulated a relationship between thyroid autoimmunity and vestibular disorders. In most cases, an appropriate control group was lacking, and the impact of thyroid functional status could not precisely be established. In recent years, two well-designed prospective studies have provided convincing evidence that the association is not random. One article reported that patients with Ménière disease (MD) had a significantly higher prevalence of positive anti-thyroid autoantibody as compared to healthy controls. Moreover, more than half of MD patients had either positive anti-thyroid or non-organ-specific autoantibody titers, compared to less than 30% of both patients with unilateral vestibular paresis without cochlear involvement and healthy controls. Another study found that patients with benign paroxysmal positional vertigo (BPPV) had significantly higher serum thyroid-stimulating hormone and antithyroid autoantibody levels than healthy controls. Additionally, almost one-fifth of euthyroid patients with HT had signs of BPPV. The published results indicate that patients with MD or BPPV are potential candidates to also develop HT. Thus, in HT patients, the presence of even slight symptoms or signs potentially related to vestibular lesions should be carefully investigated. AITD = autoimmune thyroid disease; BPPV = benign paroxysmal positional vertigo; EH = endolymphatic hydrops; HT = Hashimoto thyroiditis; L-T 4 = L-thyroxine; MD = Ménière disease; PS = Pendred syndrome; Tg = thyroglobulin; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone.

Thyroid in pregnancy: From physiology to screening.

PubMed

Springer, Drahomira; Jiskra, Jan; Limanova, Zdenka; Zima, Tomas; Potlukova, Eliska

2017-03-01

Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first trimester of pregnancy, maternal thyroxine is essential for fetal development as it supplies thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis, and maturation of the hypothalamus, pituitary and the thyroid gland; and it is almost complete by the 12th-14th gestational week. In case of maternal hypothyroidism, substitution with levothyroxine must be started in early pregnancy. After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy is about 0.3-0.5%. The prevalence of subclinical hypothyroidism varies between 4 and 17%, strongly depending on the definition of the upper TSH cutoff limit. Hyperthyroidism occurs in 0.1-1% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age with an incidence rate of 5.1-12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation processes or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. Laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. TSH in pregnancy is physiologically lower than the non-pregnant population. Results of multiple international studies point toward creation of trimester-specific reference intervals for TSH in pregnancy. Screening for hypothyroidism in pregnancy is controversial and its implementation varies from country to country. Currently, the case-finding approach of screening high-risk women is preferred in most countries to universal screening. However, numerous studies have shown that one-third to one-half of women with thyroid disorders escape the case-finding approach. Moreover, the universal screening has been shown to be more cost-effective. Screening for thyroid disorders in pregnancy should include assessment of both TSH and TPOAb, regardless of the screening approach. This review summarizes the current knowledge on physiology of thyroid hormones in pregnancy, causes of maternal thyroid dysfunction and its effects on pregnancy course and fetal development. We discuss the question of case-finding versus universal screening strategies and we display an overview of the analytical methods and their reference intervals in the assessment of thyroid function and thyroid autoimmunity in pregnancy. Finally, we present our results supporting the implementation of universal screening.

Celiac disease and other autoimmune diseases in patients with collagenous colitis.

PubMed

Vigren, Lina; Tysk, Curt; Ström, Magnus; Kilander, Anders F; Hjortswang, Henrik; Bohr, Johan; Benoni, Cecilia; Larson, Lasse; Sjöberg, Klas

2013-08-01

Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjögren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

Effects of hyperthyroidism, hypothyroidism, and thyroid autoimmunity on female sexual function.

PubMed

Oppo, A; Franceschi, E; Atzeni, F; Taberlet, A; Mariotti, S

2011-06-01

Thyroid hormones affect male and female sexual functions, but data in hypo- and hyperthyroid women are scanty. To investigate sexual function in hypo- and hyperthyroid women before and immediately after restoration of euthyroidism and in women with euthyroid Hashimoto's thyroiditis (HT). Fifty-six women with thyroid diseases (age 19-50 yr; 22 with hyperthyroidism, 17 with hypothyroidism, and 17 with euthyroid HT) and 30 age-matched healthy women. Hypoactive sexual desire, disorders of sexual arousal, vaginal lubrication, orgasm, satisfaction, and sexual pain (SPD) were assessed by Female Sexual Function Index. Serum TSH, free T4 (FT4) and thyroid autoantibodies (anti-thyroglobulin, anti-thyroperoxidase, and TSH-receptor antibodies) were assessed at the diagnosis; FT4 and TSH were repeated after treatment to confirm normalization of thyroid function. All sexual domains scores were significantly reduced (p ranging <0.0001-<0.05) in both hypo- and hyperthyroid women. Correction of hypothyroidism was associated to normalization of desire, satisfaction, and pain, while arousal and orgasm remained unchanged. In hyperthyroid women therapy normalized sexual desire, arousal/lubrication, satisfaction, and pain, while orgasm remained significantly impaired. Interestingly, euthyroid HT women displayed a significant decrease in sexual desire (p<0.0005), with no changes in the other sexual domains. Both hypo- and hyperthyroidism markedly impair female sexual function. A rapid improvement is observed with the restoration of euthyroidism, although a longer period of time may be needed for full normalization. Preliminary data suggest that thyroid autoimmunity may selectively impair sexual desire, independently from thyroid function.

Thyroglobulin autoantibodies: is there any added value in the detection of thyroid autoimmunity in women consulting for fertility treatment?

PubMed

Unuane, David; Velkeniers, Brigitte; Anckaert, Ellen; Schiettecatte, Johan; Tournaye, Herman; Haentjens, Patrick; Poppe, Kris

2013-08-01

Thyroid autoimmunity (TAI) is frequent in infertile women, but to what extent thyroglobulin autoantibodies (Tg-Abs) contribute to TAI is unclear in the literature. The aims of the present study were to determine the prevalence of TAI in women consulting for fertility problems and to investigate the impact of isolated Tg-Abs, isolated thyroid peroxidase autoantibodies (TPO-Abs), and the presence of both autoantibody types on thyroid function. Furthermore, thyroid function was compared between women with and without TAI and between infertile and fertile women. A cross-sectional data analysis nested within an ongoing prospective cohort study was performed in order to determine the prevalence of TAI in unselected women consulting our tertiary referral center for reproductive medicine (CRM). The women underwent a determination of serum thyrotropin (TSH), free thyroxine (FT4), TPO-Abs, and Tg-Abs. The cause of infertility, age, body-mass index (BMI), and smoking habits were recorded. The prevalence of TAI was 16% (163/992). In 8% of cases, both types of autoantibodies were present, in 5% isolated positive Tg-Abs were found, and 4% had isolated positive TPO-Abs (p=0.025 and p=0.003 respectively). The prevalence of TAI was significantly higher in infertile women as compared to that in fertile controls (19% vs. 13%; p=0.047). The median serum TSH level was significantly higher in the women with TAI and with isolated positive Tg-Abs compared to that in women without TAI (1.83 [1.44] and 1.90 [0.85] vs. 1.47 [0.94] mIU/L; p<0.001 respectively). The median FT4, age, BMI, and smoking habits were comparable between the study groups. The prevalence of TAI was higher in infertile women as compared to fertile women consulting our CRM. Five percent of the women had isolated positive Tg-Abs and a significantly higher serum TSH compared to that in women without TAI.

Thyroglobulin Autoantibodies: Is There Any Added Value in the Detection of Thyroid Autoimmunity in Women Consulting for Fertility Treatment?

PubMed Central

Unuane, David; Velkeniers, Brigitte; Anckaert, Ellen; Schiettecatte, Johan; Tournaye, Herman; Haentjens, Patrick

2013-01-01

Background Thyroid autoimmunity (TAI) is frequent in infertile women, but to what extent thyroglobulin autoantibodies (Tg-Abs) contribute to TAI is unclear in the literature. The aims of the present study were to determine the prevalence of TAI in women consulting for fertility problems and to investigate the impact of isolated Tg-Abs, isolated thyroid peroxidase autoantibodies (TPO-Abs), and the presence of both autoantibody types on thyroid function. Furthermore, thyroid function was compared between women with and without TAI and between infertile and fertile women. Methods A cross-sectional data analysis nested within an ongoing prospective cohort study was performed in order to determine the prevalence of TAI in unselected women consulting our tertiary referral center for reproductive medicine (CRM). The women underwent a determination of serum thyrotropin (TSH), free thyroxine (FT4), TPO-Abs, and Tg-Abs. The cause of infertility, age, body-mass index (BMI), and smoking habits were recorded. Results The prevalence of TAI was 16% (163/992). In 8% of cases, both types of autoantibodies were present, in 5% isolated positive Tg-Abs were found, and 4% had isolated positive TPO-Abs (p=0.025 and p=0.003 respectively). The prevalence of TAI was significantly higher in infertile women as compared to that in fertile controls (19% vs. 13%; p=0.047). The median serum TSH level was significantly higher in the women with TAI and with isolated positive Tg-Abs compared to that in women without TAI (1.83 [1.44] and 1.90 [0.85] vs. 1.47 [0.94] mIU/L; p<0.001 respectively). The median FT4, age, BMI, and smoking habits were comparable between the study groups. Conclusions The prevalence of TAI was higher in infertile women as compared to fertile women consulting our CRM. Five percent of the women had isolated positive Tg-Abs and a significantly higher serum TSH compared to that in women without TAI. PMID:23405888

Appearance of Graves' disease after percutaneous ethanol injection for the treatment of hyperfunctioning thyroid adenoma.

PubMed

Monzani, F; Del Guerra, P; Caraccio, N; Casolaro, A; Lippolis, P V; Goletti, O

1997-05-01

In this report we describe an unusual patient with hyperfunctioning thyroid adenoma in whom percutaneous ethanol injection (p.e.i.) therapy was followed by typical Graves' disease. His history revealed the presence of a sister with Hashimoto's thyroiditis. 99-mTc thyroid scintiscan showed focal uptake in the nodule, with suppression of extranodular parenchyma. P.e.i. therapy was followed by the development of severe hyperthyroidism. One month after a second p.e.i. cycle, recurrence of hyperthyroidism associated with diffuse 99-mTc uptake by the gland was observed. TSH-receptor and thyroglobulin autoantibodies were undetectable before p.e.i. therapy, appeared during the first cycle, and showed a further increase after the second p.e.i. therapy cycle. Though spontaneous switch to Graves' disease cannot be excluded in patients with toxic nodules, the massive release of thyroid materials from follicular cells, among these TSH-receptor antigenic components partially denatured by ethanol, may indeed trigger an autoimmune response to the TSH-receptor, thus accounting for this observation. Patients with possible autoimmune disposition, as selected by familiar history and/or laboratory markers should be carefully monitored during p.e.i. treatment.

Reversal deterioration of renal function accompanied with primary hypothyrodism.

PubMed

Dragović, Tamara

2012-02-01

Hypothyroidism is often accompanied with decline of kidney function, or inability to maintain electrolyte balance. These changes are usually overlooked in everyday practice. Early recognition of this association eliminates unnecessary diagnostic procedures that postpone the adequate treatment. Two patients with elevated serum creatinine levels due to primary autoimmune hypothyroidism, with complete recovery of creatinine clearance after thyroid hormone substitution therapy are presented. The first patient was a young male whose laboratory tests suggested acute renal failure, and the delicate clinical presentation of reduced thyroid function. The second patient was an elderly woman with a history of a long-term signs and symptoms attributed to ageing, including the deterioration of renal function, with consequently delayed diagnosis of hypothyroidism. Serum thyrotropin and thyroxin levels measurement should be done in all cases of renal failure with undefined renal desease, even if the typical clinical presentation of hypothyroidism is absent. Thyroid hormone assays sholud also be performed in all patients with chronic kidney disease whose kidney function is rapidly worsening.

Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the hanford nuclear site.

PubMed

Davis, Scott; Kopecky, Kenneth J; Hamilton, Thomas E; Onstad, Lynn

2004-12-01

Approximately 740,000 Ci (2.73 x 10(16) Bq) of iodine 131 (131I) were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. The risk of thyroid disease resulting from prolonged environmental 131I exposure is poorly understood. The Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of 131I from Hanford. Retrospective cohort study. Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992-September 1997). Participants' thyroid radiation doses from Hanford's 131I releases were estimated from interview data regarding residence and dietary histories. The cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State. Of 5199 individuals identified, 4350 were located alive and 3440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity. Thyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism. There was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest. These results do not support the hypothesis that exposure during infancy and childhood to 131I at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study.

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota.

PubMed Central

Bartley, G B

1994-01-01

Among incident cases of GO in Olmsted County, Minnesota: GO affected females six times more frequently than males (86% versus 14% of cases, respectively). The age-adjusted incidence rate was 16 cases per 100,000 population per year for females and 2.9 cases per 100,000 population for males. The peak incidence rates were bimodal, occurring in the age groups 40 to 44 years and 60 to 64 years in females and 45 to 49 years and 65 to 69 years in males. Among patients with GO, approximately 90% had Graves' hyperthyroidism, 1% had primary hypothyroidism, 3% had Hashimoto's thyroiditis, and 5% were euthyroid. Eyelid retraction was the most common ophthalmic feature of autoimmune thyroid disease, being present either unilaterally or bilaterally in more than 90% of patients at some point in their clinical course. Exophthalmos of one or both eyes affected approximately 60% of patients, restrictive extraocular myopathy was apparent in about 40% of patients, and optic nerve dysfunction occurred in either one or both eyes in 6% of patients with autoimmune thyroid disease. Only 5% of patients had the complete constellation of classic findings: eyelid retraction, exophthalmos, optic nerve dysfunction, extraocular muscle involvement, and hyperthyroidism. Upper eyelid retraction, either unilateral or bilateral, was documented in approximately 75% of patients at the time of diagnosis of GO. Lid lag also was a frequent early sign, being present either unilaterally or bilaterally in 50% of patients at the initial examination. At the time of diagnosis of GO, the most frequent ocular symptom was pain or discomfort, which affected 30% of patients. Some degree of diplopia was noted by approximately 17% of patients, lacrimation or photophobia was present in about 15% to 20% of patients, and 7.5% of patients complained of blurred vision. Decreased vision attributable to optic neuropathy was present in less than 2% of eyes at the time of diagnosis of GO. Thyroid dermopathy and acropachy accompanied GO in approximately 4% and 1% of patients, respectively. Myasthenia gravis occurred in less than 1% of patients. Superior limbic keratoconjunctivitis was documented in less than 4% of patients. The median age at the time of diagnosis of GO was 43 years (range, 8 to 88). Among patients with hyperthyroidism, 61% developed ophthalmopathy within 1 year of the onset of thyrotoxicosis. Symptoms and signs for which statistically significant changes occurred between the initial and final examinations included lacrimation, pain or ocular discomfort, photophobia, eyelid retraction, lid lag, eyelid fullness, conjunctival injection, chemosis, and exophthalmos.(ABSTRACT TRUNCATED AT 400 WORDS) Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:7886878

Diffusion and ADC-map images detect ongoing demyelination on subcortical white matter in an adult metachromatic leukodystrophy patient with autoimmune Hashimoto thyroiditis

PubMed Central

Miura, Akiko; Kumabe, Yuri; Kimura, En; Yamashita, Satoshi; Ueda, Akihiko; Hirano, Teruyuki; Uchino, Makoto

2010-01-01

Adult-onset metachromatic leukodystrophy (MLD) often shows schizophrenia- or encephalopathy-like symptoms at an early stage, such as behavioural abnormalities, cognitive impairment, mood disorders and hallucinations. The authors report the case of an adult woman with MLD who had been given antipsychotic medication for schizophrenia. In the differential diagnosis, screening of auto-antibodies was important for ruling out other encephalopathies as she had a euthyroid Hashimoto thyroiditis. Diagnosis was based the results of MRI, nerve conduction velocity, sensory evoked potential, motor evoked potential, lysosomal enzyme activity and gene analysis studies. Brain MRI showed diffuse demyelination spreading from the deep white matter to subcortical area as high signals at the edges of these lesions in diffusion and apparent diffusion coefficient-map images with the U-fibres conserved. The authors diagnosed adult-onset MLD coexisting with euthyroid autoimmune Hashimoto thyroiditis. PMID:22798296

A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients.Points that need more investigation.

PubMed

Liontiris, Michael I; Mazokopakis, Elias E

2017-01-01

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.

LYMPHOCYTIC THYROIDITIS IS ASSOCIATED WITH INCREASED NUMBER OF BENIGN CERVICAL NODES AND FEWER CENTRAL NECK COMPARTMENT METASTATIC LYMPH NODES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

PubMed

Donangelo, Ines; Walts, Ann E; Bresee, Catherine; Braunstein, Glenn D

2016-10-01

Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection. From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013. Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT. Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear. CCND = central compartment node dissection DTC = differentiated thyroid cancer HT = Hashimoto thyroiditis LT = lymphocytic thyroiditis TgAb = thyroglobulin antibody TPO = thyroid peroxidase.

Polyinosine-polycytidylic acid promotes excessive iodine intake induced thyroiditis in non-obese diabetic mice via Toll-like receptor 3 mediated inflammation.

PubMed

Shi, Ya-nan; Liu, Feng-hua; Yu, Xiu-jie; Liu, Ze-bing; Li, Qing-xin; Yuan, Ji-hong; Zang, Xiao-yi; Li, Lan-ying

2013-02-01

Excessive iodine intake and viral infection are recognized as both critical factors associated with autoimmune thyroid diseases. Toll-like receptors (TLRs) have been reported to play an important role in autoimmune and inflammatory disorders. In this study, we aimed to clarify the possible mechanism of TLR3 involved in polyinosine-polycytidylic acid (poly(I:C)) promoting excessive iodine intake induced thyroiditis in non-obese diabetic (NOD) mice. Both NOD and BALB/c mice were randomly assigned to four groups: control group (n = 5), high iodine intake (HI) group (n = 7), poly(I:C) group (n = 7) and combination of excessive iodine and poly(I:C) injection (HIP) group (n = 7). After 8 weeks, mice were weighed and blood samples were collected. All the mice were sacrificed before dissection of spleen and thyroid gland. Then, thyroid histology, thyroid secreted hormone, expression of CD3(+) cells and TLR3 as well as inflammatory mRNA level were evaluated. Both NOD and BALB/c mice from HI and HIP group represented goiter and increasing thyroid relative weight. Thyroid histology evidence indicated that only HIP group of NOD mice showed severe thyroiditis with lymphocytes infiltration in majority of thyroid tissue, severe damage of follicles and general fibrosis. Immunofluorescence staining results displayed a large number of CD3(+) cells in HIP NOD mice. Real-time polymerase chain reaction (PCR) results suggested interferon (IFN)-α increased over 30 folds and IFN-γ expression was doubled compared with control group, but interleukin (IL)-4 remained unchanged in HIP group of NOD mice thyroid. Meanwhile, over one third decrease of blood total thyroxine (TT4) and increased thyroid-stimulating hormone (TSH) was observed in HIP group of NOD mice. Only HIP group of NOD mice represented significantly elevation of TLR3 expression. Poly(I:C) enhanced excessive dietary iodine induced thyroiditis in NOD mice through increasing TLR3 mediated inflammation.

15-Year old girl with APS type IIIc, 12 months post-thymectomy remission of myasthenia.

PubMed

Jamiołkowska, Milena; Bossowski, Artur

2017-01-01

Polyglandular autoimmune syndromes (PAS) is a group of heterogenous conditions characterized by the association of at least two organ-specific autoimmune disorders, concerning both endocrine and non-endocrine organs. Type III is defined as the combination of autoimmune thyroid disease and other autoimmune condition (other than Addison's disease) and is divided into four subtypes. We describe a teenage female patient - with the family history of autoimmune diseases, who has simultaneously developed the symptoms of autoimmune thyroid disease with the clinical picture of hyperthyroidism and myasthenia gravis at the age of fifteen. Graves' disease was diagnosed approximately 2 months before myasthenia. Co-occurance of those two diseases allowed us to diagnose PAS type IIIC, however it caused specific diagnostic and treatment difficulties. Furthermore, several months after the diagnosis the patient was found to be GAD-Ab positive, whilst the glycaemic control remained normal. No evidence of other autoimmune conditions was observed. This patient received the standard GD and MG treatment. When the CT scan revealed thymus enlargement, thymectomy was performed. After the surgery we have observed not only remission of MG, but also a significant decrease of TRAb as well, that lasted for a year after the thymectomy. Our patient's case suggests that in patients diagnosed with PAS, the organ-specific Ab screening can help identify other latent and subclinical autoimmune diseases before clinical symptoms develop. The achievement of post-thymectomy remission of both MG and GD may indicate a close immunological relationship between PAS components. © Polish Society for Pediatric Endocrinology and Diabetology.

Autoimmune Encephalitis Following Bone Marrow Transplantation.

PubMed

Rathore, Geetanjali S; Leung, Kathryn S; Muscal, Eyal

2015-09-01

Neurological complications, especially encephalopathy and seizures, are commonly seen in bone marrow transplant patients. Infections, chemotoxicity, graft versus host disease, or secondary central nervous system malignancies are the most common underlying etiologies. There is increased awareness that autoimmune encephalitis may cause neurological dysfunction in immunocompetent children. The potential role of such a mechanism in children undergoing bone marrow transplantation is unknown. We report a boy who developed autoimmune encephalitis with voltage-gated potassium channel-associated and thyroid autoantibodies subsequent to transplantation. A 7-year-old boy presented with a change in behavior, poor attention, cognitive deficits, and abnormal movements 15 months after undergoing transplantation for idiopathic aplastic anemia. He had clinical and subclinical seizures and brain magnetic resonance imaging hyperintensities bilaterally in the uncal regions. His evaluation revealed high titers of voltage-gated potassium channel, leucine-rich glioma-inactivated 1 protein, and thyroglobulin antibodies suggestive of autoimmune limbic encephalitis. He showed significant improvement in behavior and neuropsychological testing and has remained seizure-free on levetiracetam after immunotherapy with corticosteroids and intravenous immunoglobulin. Systemic autoimmune manifestations in bone marrow transplant patients have been well-documented, but autoimmune encephalitis after transplantation has yet to be described in children. Copyright © 2015 Elsevier Inc. All rights reserved.

Treatment of thyroid disorders before conception and in early pregnancy: a systematic review.

PubMed

Vissenberg, R; van den Boogaard, E; van Wely, M; van der Post, J A; Fliers, E; Bisschop, P H; Goddijn, M

2012-07-01

Thyroid disorders are associated with pregnancy complications. Universal screening is currently not recommended because of a lack of evidence on the effectiveness of treatment. Women with hyperthyroidism and hypothyroidism evidently require treatment but this is less clear for women with subclinical hypothyroidism and thyroid autoimmunity. Therefore, we conducted a systematic review to provide a comprehensive overview on the available treatment interventions. Relevant studies were identified by searching Medline, EMBASE and Cochrane Controlled Trials Register, published until December 2011. From a total of 7334 primary selected titles, 22 articles were included for the systematic review and 11 were appropriate for meta-analyses. Eight studies reported on hyperthyroidism. Propylthiouracil (PTU) and methimazole reduce the risk for preterm delivery [risk ratio (RR): 0.23, confidence interval (CI): 0.1-0.52], pre-eclampsia (RR: 0.23, CI: 0.06-0.89) and low birthweight (RR: 0.38, CI: 0.22-0.66). The nine studies that reported on clinical hypothyroidism showed that levothyroxine is effective in reducing the risk for miscarriage (RR: 0.19, CI: 0.08-0.39) and preterm delivery (RR: 0.41, CI: 0.24-0.68). For treatment of subclinical hypothyroidism, current evidence is insufficient. The five studies available on thyroid autoimmunity showed a not significant reduction in miscarriage (RR: 0.58, CI: 0.32-1.06), but significant reduction in preterm birth by treatment with levothyoxine (RR: 0.31, CI: 0.11-0.90). For hyperthyroidism, methimazole and PTU are effective in preventing pregnancy complications. For clinical hypothyroidism, treatment with levothyroxine is recommended. For subclinical hypothyroidism and thyroid autoimmunity, evidence is insufficient to recommend treatment with levothyroxine. The overall lack of evidence precludes a recommendation for universal screening and is only justified in a research setting.

Effects of latent toxoplasmosis on autoimmune thyroid diseases in pregnancy.

PubMed

Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

2014-01-01

Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Cross-sectional study in 1248 consecutive pregnant women in the 9-12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases.

Effects of Latent Toxoplasmosis on Autoimmune Thyroid Diseases in Pregnancy

PubMed Central

Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

2014-01-01

Background Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Methods Cross-sectional study in 1248 consecutive pregnant women in the 9–12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Results Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Conclusions Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases. PMID:25350671

Avian models with spontaneous autoimmune diseases

PubMed Central

Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

2012-01-01

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

Involvement of endocrine system in a patient affected by glycogen storage disease 1b: speculation on the role of autoimmunity.

PubMed

Melis, Daniela; Della Casa, Roberto; Balivo, Francesca; Minopoli, Giorgia; Rossi, Alessandro; Salerno, Mariacarolina; Andria, Generoso; Parenti, Giancarlo

2014-03-19

Glycogen storage disease type 1b (GSD1b) is an inherited metabolic defect of glycogenolysis and gluconeogenesis due to mutations of the SLC37A4 gene and to defective transport of glucose-6-phosphate. The clinical presentation of GSD1b is characterized by hepatomegaly, failure to thrive, fasting hypoglycemia, and dyslipidemia. Patients affected by GSD1b also show neutropenia and/or neutrophil dysfunction that cause increased susceptibility to recurrent bacterial infections. GSD1b patients are also at risk for inflammatory bowel disease. Occasional reports suggesting an increased risk of autoimmune disorders in GSD1b patients, have been published. These complications affect the clinical outcome of the patients. Here we describe the occurrence of autoimmune endocrine disorders including thyroiditis and growth hormone deficiency, in a patient affected by GSD1b. This case further supports the association between GSD1b and autoimmune diseases.

The association between Helicobacter pylori infection, type 1 diabetes mellitus, and autoimmune thyroiditis.

PubMed

Zekry, Osama A; Abd Elwahid, Hassan A

2013-12-01

Type 1 diabetes mellitus (T1DM) can be associated with an increased prevalence of Helicobacter pylori infection, which could contribute to the pathogenesis of autoimmune thyroiditis observed in this disease. The aim of this study was to assess the relationship between H. pylori infection and T1DM and to identify of the interconnection between H. pylori infection and autoimmune thyroiditis in patients with T1DM. A case-control design was used. The study group included 60 children and adolescents with T1DM who were selected from the pediatric outpatient clinic of Suez Canal University Hospital by a systematic random sampling method. The control group included 60 healthy children and adolescents matched for age and sex and selected from among relatives (brothers or cousins) of the patients with T1DM. The study participants were subjected to several investigations including estimation of levels of HbA1c, thyroid stimulating hormone (TSH), T3, T4, anti-thyroglobulin (anti-Tg), and anti-thyroid peroxidase (anti-TPO). The mean age of the patients with T1DM was 12.53±2.35 years, whereas that of the control group was 12.30±1.98 years, with no statistically significant difference between the two groups. The patients with diabetes had significantly higher levels of H. pylori IgG, TSH, anti-TPO, and anti-Tg (20.43±14.84  μ/ml, 4.03±1.53 mIu/l, 14.98 ±5.04 Iu/ml, and 5.66±3.37 Iu/ml, respectively) and significantly lower levels of T3 and T4 (120±15.86 μg/dl and 4.93±0.93 μg/dl, respectively) compared with the control group. In addition, the seroprevalence rate of H. pylori, anti-Tg, and anti-TPO was significantly higher in diabetic patients, and the duration of diabetes was significantly longer in H. pylori-positive patients with higher levels of HbA1c, insulin requirement, TSH, anti-TPO, and anti-Tg. The association between H. pylori infection and autoimmune thyroiditis in patients with T1DM was revealed in this study. Hence, screening and treatment of H. pylori infection in T1DM patients is recommended.

A 27-year-old woman diagnosed as polycystic ovary syndrome associated with Graves' disease.

PubMed

Jung, Jung Hwa; Hahm, Jong Ryeal; Jung, Tae Sik; Kim, Hee Jin; Kim, Ho Soo; Kim, Sungsu; Kim, Soo Kyoung; Lee, Sang Min; Kim, Deok Ryong; Choi, Won Jun; Seo, Yeong Mi; Chung, Soon Il

2011-01-01

Polycystic ovary syndrome (PCOS) and Graves' disease are the common causes of menstrual irregularity leading to infertility in women of child-bearing age. A 21-year-old female patient visited us with complaints of oligomenorrhea and hand tremor. She was diagnosed as having PCOS and hyperthyroid Graves' disease, simultaneously. She had low body weight (BMI: 16.4 kg/m(2)), mild hirsutism, and thyrotoxicosis. The patient was treated with anti-thyroid drug and beta-blocker for about two years, and then recovered to normal thyroid function. Although some studies have suggested a connection between PCOS and autoimmune thyroiditis, no study indicated that PCOS is associated with Graves' disease until now. Here, we describe the first case report of a lean woman with normal insulin sensitivity presenting PCOS and Graves' disease simultaneously.

[Hashimoto thyroiditis may be associated with a subset of patients with systemic sclerosis with pulmonary hypertension].

PubMed

Costa, Ciliana Cardoso B; Medeiros, Morgana; Watanabe, Karen; Martin, Patricia; Skare, Thelma L

2014-01-01

Recent studies show an association between autoimmune thyroiditis and systemic sclerosis (SSc) and suggest that this condition may interfere with the ES phenotype. However these studies evaluate the autoimmune thyroiditis as a whole and none of them specifically addresses Hashimoto's thyroiditis (HT) in SSc. To investigate the presence of HT in SSc patients and its possible association with disease manifestations. Clinical manifestations of hypothyroidism, TSH and anti-thyroid auto antibodies (anti-TPO. anti TBG and TRAb) were studied in 56 patients with SSc. SSc patients with HT were compared with SSc patients without thyroiditis. HT was observed in 19.64% of patients with SSc. No association was observed between HT and the different forms of disease or profile of autoantibodies. Likewise, there was no difference between the mean modified Rodnan score and presence of Raynaud's phenomenon, scars, digital necrosis, myositis, arthritis, sicca symptoms, esophageal dysmotility and scleroderma renal crisis when the groups were compared. On the other hand, patients with HT had higher frequency of pulmonary hypertension in relation to patients without HT (66.6% vs 22.5%, p=0.016). In the studied sample patients with ES and HT had higher prevalence of pulmonary hypertension. Long-term follow-up studies with a larger number of TH and SSc patients are needed to confirm these data. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Secondary and tertiary preventions of thyroid disease.

PubMed

Azizi, Fereidoun; Mehran, Ladan; Hosseinpanah, Farhad; Delshad, Hossein; Amouzegar, Atieh

2018-05-01

Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

A case of pernicious anemia requiring differential diagnosis of autoimmune hemolytic anemia complication.

PubMed

Todo, Saki; Okamoto, Kohei; Sugimoto, Takeshi; Takahashi, Toshimasa; Nakagawa, Yasushi; Arai, Takashi; Nishiyama, Katsuhito; Hara, Kenta; Yasutomo, Yoshiro; Yokono, Koichi

2017-09-01

An 80-year-old female was admitted to our hospital due to malaise. The initial diagnosis on admission was pernicious anemia (PA), Hashimoto thyroiditis and autoimmune atrophic gastritis. Autoimmune hemolytic anemia was suspected because direct antiglobulin test (DAT) was positive. Treatment with vitamin B12 improved anemia, with the disappearance of hemolysis. In some cases, PA patients with positive DAT may have hemolysis without the involvement of the autoimmune mechanism. Therefore, it is important to carefully assess PA patients with hemolysis and positive DAT for the prevention of unnecessary administration of steroid therapy.

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

A combined case of macroprolactinoma, growth hormone excess and Graves' disease.

PubMed

Hussein, Z; Tress, B; Colman, P G

2005-06-01

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Association of antithyroid peroxidase antibody with fibromyalgia in rheumatoid arthritis.

PubMed

Ahmad, Jowairiyya; Blumen, Helena; Tagoe, Clement E

2015-08-01

To investigate how autoimmune thyroiditis (ATD) affects the clinical presentation of established rheumatoid arthritis (RA) with particular reference to fibromyalgia and chronic widespread pain (CWP). A cohort of 204 patients with RA for whom the presence or absence of autoimmune thyroid antibodies was documented was examined for the relationships between thyroid autoantibodies and fibromyalgia or CWP. We identified 29 % who tested positive for antithyroid peroxidase antibodies (TPOAb). The anti-thyroglobulin antibody (TgAb) was found in 24 %. Among the thyroid autoantibody-positive patients, 40 % had a diagnosis of fibromyalgia or CWP versus 17 % for antibody negative patients. Logistic regression analyses (adjusted by age, sex, diabetes and BMI) indicated that TPOAb-positive patients were more likely to have fibromyalgia or CWP, with an odds ratio (OR) of 4.641, 95 % confidence interval (CI) (2.110-10.207) P < .001. Adjusting for spinal degenerative disc disease did not change the association with fibromyalgia, OR 4.458, 95 % CI (1.950-10.191), P < .001. The OR between TgAb and fibromyalgia was not significant (P > .05). Additional logistic regression analyses (adjusted by age, sex and BMI) indicated a significant relationship between TPOAb and fibromyalgia or CWP in patients without diabetes and those without hypothyroidism (OR of 4.873, 95 % CI (1.877-12.653), P = .001 and OR of 4.615 95 % CI (1.810-11.770), P = .001, respectively). There may be a positive association between the ATD antibody TPOAb, and fibromyalgia syndrome and CWP in patients with established RA.

Evidence for the possible occurrence of Grave's disease in a blue-eyed black lemur (Eulemur flavifrons).

PubMed

Quintard, Benoît; Giorgiadis, Marine; Feirrera, Xavier; Lefaux, Brice; Schohn, Christophe; Lemberger, Karin

2018-03-01

The blue-eyed black lemur (Eulemur flavifrons) is classified by the International Union for Conservation of Nature (IUCN) as critically endangered. A 23-year-old male housed at Mulhouse Zoo presented with lethargy, polyphagia, alopecia, and chronic weight loss. Clinical examination suggested an endocrine pathology such as hyperthyroidism. Secondary examinations included cervical ultrasound, thyroid biopsy, and scintigraphy. The latter revealed elevated thyroid activity. Blood analysis was performed to measure the level of anti-receptor thyroid-stimulating hormone antibodies, which allowed us to test the autoimmune hypothesis. The high level of antibodies together with levels of thyroid-stimulating hormone and the scintigraphy images led to the diagnosis of Grave's disease. Carbimazole treatment followed by thyroidectomy resulted in a quick weight gain and general improvement in health status. The following breeding season, the treated individual sired an offspring. To the authors' knowledge, this is the first report of likely Grave's disease in a non-human primate.

Pendulum swings from hypo- to hyperthyroidism: thyrotoxicosis after severe hypothyroidism following neck irradiation in a patient with a history of Hodgkin's lymphoma.

PubMed

Lewandowski, Krzysztof; Dąbrowska, Katarzyna; Makarewicz, Jacek; Lewiński, Andrzej

2016-01-01

A change in a thyrometabolic state from severe hypothyroidism to thyrotoxicosis is very uncommon, but possible in some circumstances. A 27-year old female presented with clinical and biochemical thyrotoxicosis with a previous history chemo- and radiotherapy (including the neck region) for a Hodgkin's lymphoma (at the age of 18). At the age of 20 this was followed by severe hypothyrodism [TSH > 100 μIU/mL (reference range: 0.27-4.2)]. She was stated on L-thyroxine, but the dose was later reduced and subsequently discontinued. She had significantly elevated titres of both anti-thyroid peroxidase antibodies and anti-TSH-receptor antibodies throughout the course of disease. Thyroid scintigraphy revealed a normal and homogenous iodine uptake. We suspect that a gradual switch from thyroid-blocking to thyroid-stimulating antibodies resulted in development of an overt thyrotoxicosis, possibly with a contributory effect of neck irradiation on her autoimmune status.

Search for relevant indications for selenium supplementation in thyroid diseases.

PubMed

Wojciechowska-Durczynska, Katarzyna; Lewinski, Andrzej

2017-08-01

Selenium plays a significant role in the thyroid function and its deficiency is considered by some authors to be a cause of thyroid disorders. The potential therapeutic influence of selenium supplementation in thyroid disease was investigated in several studies and some results were encouraging, however results were inconsistent and did not allow conclusion to be drawn. For that reason, we have performed a review study on relevance of selenium supplementation in thyroid disease. Till now, there is no strong evidence that selenium supplementation leads to clinical improvement in the course of autoimmune thyroiditis, nodular goitre or thyroid cancer. On the other hand, there is some evidence that selenium is effective in the treatment of orbitopathy; thus, the European Group on Graves' Orbitopathy (EUGOGO) recommends selenium administration in mild active orbitopathy.

[Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

PubMed

Itoh, Mitsuyasu

2012-11-01

Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

355 Ocular Muscles Myopathy Associated with Autoimmune Thyroiditis. Case Reports

PubMed Central

Vargas-Camaño, Eugenia; Castrejon-Vázquez, Isabel; Plazola-Hernández, Sara I.; Moguel-Ancheita, Silvia

2012-01-01

Background Thyroid-associated orbitopathy is commonly associated with Graves' disease with lid retraction, exophthalmos, and periorbital swelling, but rarely with autoimmune thyroiditis or euthyroid state. We reviewed 3 cases from our hospital whose antibodies to anti-receptor of TSH were normal. Methods Case 1: 60 year-old non-diabetic woman with bilateral glaucoma in treatment, recurrent media otitis and euthyroidism, acute onset of painless diplopia, and lid ptosis in the left eye. MRI of orbit showed increased size of the III right cranial pair and high levels of thyroid autoantibodies (Tab) anti-tiroglobulin (ATG) 115.1, anti-thyroid peroxidase (ATPO) 1751 U/mL. She started oral deflazacort 30 mg each 3 days. Sixty days later, complete remission of eye symptoms correlated with lower auto-antibodies level (ATG 19 ATPO 117). Case 2: 10 year-old girl. At age 8, she had diplopia, lid ptosis and limitations of upper gaze in the left eye. The neurological study discarded ocular myasthenia; with thyroid goitier, and hypothyrodism, she started oral levothyroxin. At age 10 with normal IRM Botulinic toxin was injected, without change. High levels of Tab were found, ATG 2723, ATPO 10.7. She started oral deflazacort 30 mg each 3 days, azathioprin 100 mg, daily. Actually, Tab levels are almost normal, but she remains with ocular alterations. Case 3: 56 year-old woman, Grave´s disease with exophtalmos in 1990, treated with I131 and immunosupression, with good outcome; obesity, hypertension and bilateral glaucoma in treatment. She suddenly presented diplopia and IV pair paresia of the right eye. A year later, ATb were found slightly elevated, ATG 100 years ATPO 227; despite prednisone 50 mg, each 3 days and azathioprin 150 mg/daily treatment, a surgical procedure was required for relieve the ocular symptoms. Results We found only 3 cases previously reported with this type of eye thyroid disease. Is important to note that awareness of this atypical form of orbitopathy Conclusions Early recognition facilitates successful treatment (Case 1) or persistent disease when diagnosis is delayed (Cases 2 and 3).

Recurrent hypoglycaemia in type-1 diabetes mellitus may unravel the association with Addison's disease: a case report.

PubMed

Passanisi, Stefano; Timpanaro, Tiziana; Lo Presti, Donatella; Caruso-Nicoletti, Manuela

2014-09-12

Primary adrenocortical insufficiency or Addison's disease is caused by a progressive destruction of the adrenal cortex, resulting into a reduction of glucocorticoids, mineralocorticoids, and androgens. Autoimmune Addison's disease is the most common etiological form, accounting for about 80% of all cases. We describe the case of a 16-year-old Caucasian boy affected by type-1 diabetes mellitus and autoimmune thyroiditis, who experienced recurrent hypoglycaemia as presenting symptom of Addison's disease. Hypoglycaemia is not a common presenting feature of Addison's disease, both in patients with type-1 diabetes mellitus and in non-diabetic patients. However, hypoglycaemia may occur in association with primary and secondary glucocorticoid deficiency as a result of an enhanced insulin sensitivity. Hypoglycaemia is the most common acute complication of insulin therapy in patients with type-1 diabetes mellitus. Addison's disease has been described in approximately 0.5% of patients with type-1 diabetes mellitus, being more frequent in females and occurring in middle-aged patients. An association among type-1 diabetes mellitus, autoimmune thyroiditis, and Addison's disease is found in the "Schmidt's syndrome", a rare disorder that may occur in the paediatric age. Our case suggests that the presence of Addison's disease should be taken into consideration in patients with type-1 diabetes mellitus and frequent episodes of hypoglycaemia. We wish to highlight that there are no specific indications to screen for the association between Addison's disease and type-1 diabetes mellitus, although an early diagnosis of Addison's disease in diabetic patients would prevent the morbidity and potential mortality of this association.

High prevalence of antithyroid peroxidase and antiparietal cell antibodies among patients with type 1 diabetes mellitus attending a tertiary diabetes centre in South Africa.

PubMed

Paruk, Imran M; Ganie, Yasmeen; Maharaj, Sureka; Pirie, Fraser J; Naidoo, Vasudevan G; Nkwanyana, Ntombifikile M; Dinnematin, Hilary L; Ramdial, Pratistadevi K; Motala, Ayesha A

2017-06-01

Data on the prevalence of autoimmune thyroid disease (AITD) and gastric autoimmunity in type 1 diabetes mellitus (T1DM) in Africa are limited. The aim of this study was to assess the prevalence of antithyroid peroxidase (TPO-A) and antiparietal cell antibody (PCA) in patients with T1DM at a tertiary diabetes clinic in Durban, South Africa. This was a cross-sectional observational study among subjects attending the adult T1DM clinic at Inkosi Albert Luthuli Hospital. Information about history and clinical examination was collected. Blood tests included glutamic acid decarboxylase antibody (GADA), TPO-A, PCA, vitamin B 12 , folate, ferritin, thyroid stimulating hormone (TSH), free thyroxine, lipids and HbA1c. A total of 202 (M:F, 90:112) patients were recruited. The ethnic composition was African (black) (56.4%; n=114), Indian (31.7%; n=64), white (4.5%; n=9) and coloured (mixed race) (7.4%; n=15). Mean age and mean duration of diabetes were 26.4±11.4 and 10.7±9.1 years, respectively. Mean body mass index was 21.6±6.3 kg/m 2 . GADA was positive in 63.37% (n=128). The prevalence of TPO-A was 18.9% (n=39) and PCA 8.9% (n=17). The prevalence of overt hypothyroidism, subclinical hypothyroidism and Graves' disease was 10.9%, 2.5% and 1.5%, respectively; vitamin B 12 deficiency was noted in 3.5% (n=7) and iron deficiency in 19.3% (n=39). Among patients with T1DM in this study, there was a high prevalence of coexistent AITD and gastric autoimmunity. Screening for hypothyroidism and thyroid autoimmunity should be undertaken in all patients at initial presentation. However, to assess the feasibility and optimal timing of subsequent testing in the African setting with limited resources, more collaborative research with longitudinal studies is required. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

PubMed

Elnady, Basant M; Kamal, Naglaa M; Shaker, Raneyah H M; Soliman, Amal F; Hasan, Waleed A; Alghamdi, Hamed A; Algethami, Mohammed M; Jajah, Mohamed Bilal

2016-09-01

Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001).ATD is more associated with rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus and RA, with early referral to rheumatologists for close follow-up and early diagnoses for appropriate disease management of the disease, as early disease control will allow better quality of life.

Comorbid Latent Adrenal Insufficiency with Autoimmune Thyroid Disease.

PubMed

Yamamoto, Toshihide

2015-09-01

Autoimmune thyroid disease (ATD) has been occasionally observed in patients with primary adrenal insufficiency (PAI). In contrast, less than 20 cases of comorbid PAI with ATD have been found in the English literature. One conceivable reason is difficulty in detecting latent PAI. Information of clinical presentation and diagnostics is sought to facilitate diagnosis of latent PAI. Latent PAI was pursued in 11 patients among 159 ATD patients. All of them were maintained in a euthyroid state. Except for one patient with nonrheumatic musculoskeletal symptoms, the other patients, who were asymptomatic in their daily lives, presented with recurrent nonspecific gastrointestinal symptoms or fatigue in stress-associated circumstances. Morning cortisol level <303 nmol/l was used as an inclusion criterion. Their basal adrenocorticotropic hormone levels were normal. The adrenal status was examined by a provocation test, either an insulin-induced hypoglycemia test or a 1-μg intravenous corticotrophin test. Eleven patients showed subnormal cortisol response. They were supplemented with hydrocortisone of doses ≤15 mg/day. After a few months of supplementation, PAI was confirmed by another provocation test. Three patients were excluded because of dissociation of two provocation tests. Comorbid latent PAI with ATD was pursued from the symptoms stated above and proven by two provocation tests; it was found in 5% (8/159) of the patients. When patients with ATD are troubled by recurrent stress-associated gastrointestinal or constitutional symptoms or nonrheumatic musculoskeletal symptoms which have remained unrelieved by adjustment of thyroid medication, these symptoms may be a manifestation of comorbid latent PAI. It is worth investigating such patients for latent PAI.

Characterization of thyroid function and antithyroid antibody tests among Saudis

PubMed Central

Jammah, Anwar A.; Alshehri, Anwar S.; Alrakhis, Afaf A.; Alhedaithy, Asma S.; Almadhi, Asma M.; Alkwai, Hala M.; Alhamad, Maram M.; Alzahrani, Saad H.

2015-01-01

Objective: To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population. Methods: A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity. Results: Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (p<0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies. Conclusion: The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies. PMID:25987111

Characterization of thyroid function and antithyroid antibody tests among Saudis.

PubMed

Jammah, Anwar A; Alshehri, Anwar S; Alrakhis, Afaf A; Alhedaithy, Asma S; Almadhi, Asma M; Alkwai, Hala M; Alhamad, Maram M; Alzahrani, Saad H

2015-06-01

To determine the reference intervals for thyroid function tests and the prevalence of thyroid autoimmunity in the Saudi population.   A cross-sectional prospective study was conducted in King Khalid University Hospital, Riyadh, Saudi Arabia from January to June 2013. History and physical examination were obtained. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured by Electro-chemiluminescence Immunoassay system-assay. Anti-thyroperoxidase, and anti-thyroglobulin antibodies were measured using enzyme-linked immunosorbent-assay. Subjects with previous or a family history of thyroid disorders, those taking medications affecting thyroid function, pregnant or lactating women, and those with goiter were excluded. Individuals with positive antibodies were excluded from the final analysis of the TSH reference range, but were used to determine the prevalence of thyroid autoimmunity.   Out of 337 Saudi subjects initially screened, 132 (aged 13-60 years) were candidates for reference calculation, the mean±standard deviation, and (2.5th-97.5th) percentile of TSH (mIU/L) was 1.96±0.9 (0.59-4.37), for FT4 (pmol/L) was 15.47±1.83 (12.04-19.13), and for FT3 (pmol/L) was 5.22±0.7 (4.07-6.76). The TSH was higher in the antibodies positive group (2.5±1.17 mIU/L) compared with the negative one (1.96±0.9 mIU/L) (p less than 0.05). Finally, 26% of subjects were tested positive for antithyroid antibodies.   The TSH reference range was similar to laboratory references. Thyroid antibodies were prevalent in Saudis, necessitating further work in larger scale studies.

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus.

PubMed

Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

2015-12-01

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients.

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus

PubMed Central

Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

2015-01-01

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. Objectives: The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. Patients and Methods: This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. Results: The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Conclusions: Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients. PMID:26756002

Cutaneous signs of thyroid disease.

PubMed

Mullin, G E; Eastern, J S

1986-10-01

Hyperactivity of the sympathetic nervous system produces many of the skin changes of hyperthyroidism, while the hypometabolic state and the accumulation of mucopolysaccharides in the dermis are responsible for hypothyroid cutaneous manifestations. Acropachy, atopic eczema, localized myxedema and nail changes are associated with thyrotoxicosis. Vitiligo may be seen in all three thyroid diseases of autoimmune origin. Hyperpigmentation, pruritus and urticaria are associated with hyperthyroidism.

Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in identifying susceptibility genes and regions.

PubMed

Brand, Oliver J; Gough, Stephen C L

2011-12-01

The autoimmune thyroid diseases (AITD) include Graves' disease (GD) and Hashimoto's thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology.

Immunogenetic Mechanisms Leading to Thyroid Autoimmunity: Recent Advances in Identifying Susceptibility Genes and Regions

PubMed Central

Brand, Oliver J; Gough, Stephen C.L

2011-01-01

The autoimmune thyroid diseases (AITD) include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology. PMID:22654554

Peginterferon Lambda-1a Is Associated with a Low Incidence of Autoimmune Thyroid Disease in Chronic Hepatitis C.

PubMed

Fredlund, Paul; Hillson, Jan; Gray, Todd; Shemanski, Lynn; Dimitrova, Dessislava; Srinivasan, Subasree

2015-11-01

Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a phase-2b study, 525 treatment-naive patients with chronic hepatitis C virus (HCV) infection received ribavirin and Lambda interferon (120, 180, or 240 μg) or alfa interferon (180 μg) for 24 (genotypes 2 and 3) or 48 (genotypes 1 and 4) weeks. Retrospective analysis found that adverse events of MedDRA-coded thyroid dysfunction and abnormal levels of thyroid-stimulating hormone (TSH) were significantly more frequent with alfa versus Lambda (12% versus 2.6% and 15.2% versus 3.4%, respectively, both P<0.0001). Most Lambda recipients with abnormal TSH had levels below the lower limit of normal; the frequency of low and high TSH was similar in alfa recipients with abnormal TSH. Blinded review by an endocrinologist found that new-onset primary hypothyroidism or painless thyroiditis was less frequent with Lambda versus alfa (0.5% and 1.8% versus 5.3% and 7.5%, respectively, P<0.0001). Most TSH elevations reflected new-onset hypothyroidism requiring treatment, while most markedly suppressed TSH values reflected probable painless thyroiditis and resolved without sequelae. In conclusion, HCV-infected patients treated with Lambda/ribavirin experienced fewer adverse events of thyroid dysfunction compared with patients treated with alfa/ribavirin.

[DIAGNOSTIC AND TREATMENT STRATEGY IN FOLLICULAR TUMOR OF THYROID GLAND].

PubMed

Mikhaĭlova, M V; Zubarovskiĭ, I N; Osipenko, S K

2015-01-01

The article is based on the treatment results of 44 patients with follicular tunor of thyroid gland. A staged morphological assessment of thyroid nodes was performed for all patients: in case of preoperative fine-needle biopsy, urgent intraoperative study and according to results of final histological research. The urgent histological study of surgical material was conducted for 44 patients with diagnosis "follicular tumor" according to fine-needle biopsy. The data of final histological study were matched with findings of intraoperative research. A micro-follicular adenoma was detected in 22 patients (50%) and 6 (13,6%) patients had this diagnosis combined with autoimmune thyroiditis. The general part of patients didn't changed in final study, but the rate of diagnosis "micro-follicular adenoma against the background of autoimmune thyroiditis" increased. Papillary carcinoma was revealed in 5 (11,4%) patients and follicular cancer had 4 (9,1%) patients detected in intraoperative study and 3 (6,8%) more patients according to data of final research. The histopathologic feature of colloid goiter was observed in 7 (15,9%) cases and a part of such patients reduced to 6,8% during final study. One of the patients (2,3%) had final diagnosis "oncocytoma". In case of thyroid nodules detection the needle biopsy should be carried out regardless to the size of nodule. The authors recommended performing the surgery with the urgent histological study in case of undetermined histological report. The following surgical strategy was specified by the results of the urgent histological report.

Evaluation of Xerostomia and salivary flow rate in Hashimoto’s Thyroiditis

PubMed Central

Shirzad, Nooshin; Moosavi, Mahdieh-Sadat

2016-01-01

Background One of the most common causes of hypothyroidism is Hashimoto´s Thyroiditis (HT). Early detection of dry mouth is critical in preserving and promoting systemic and oral health. In this study we have assessed, for the first time, salivary function and xerostomia in HT patients who have not been involved with Sjögren´s syndrome. Material and Methods HT was diagnosed in 40 patients based on clinical findings and positive anti-thyroid peroxidase antibodies (anti-TPO). Controls, matched by sex, age and body mass index (BMI), and with no history of thyroid disease, were selected. A questionnaire was used for diagnosis of xerostomia. Saliva samples were taken between 8 a.m. and 9 a.m., and at least 2 hours after the last intake of food or drink. The flow rate was calculated in milliliters per minute. Results Xerostomia was significantly higher in patients with HT. Unstimulated salivary flow rate was significantly lower in the HT group. Stimulated salivary flow rate was lower in HT group, but the difference was not significant. Conclusions The patients with HT experienced xerostomia, and their salivary flow rate was diminished. Spitting the saliva then assessing salivary flow rate based on milliliter per minute is non-invasive, fast, and simple for chair-side diagnosis of dry mouth. Autoimmune diseases can be accompanied by salivary gland dysfunction. This may be due to the effect of cytokines in the autoimmune process or because of thyroid hormone dysfunctions. Key words:Thyroid, salivary gland, xerostomia. PMID:26595829

Myasthenia gravis in a patient affected by glycogen storage disease type Ib: a further manifestation of an increased risk for autoimmune disorders?

PubMed

Melis, D; Balivo, F; Della Casa, R; Romano, A; Taurisano, R; Capaldo, B; Riccardi, G; Monsurrò, M R; Parenti, G; Andria, G

2008-12-01

Glycogen storage disease type Ib (GSD Ib, OMIM 232220) is an inborn disorder of glucose metabolism, caused by mutations in the G6PT gene, encoding a glucose 6-phosphate transporter (G6PT). GSD Ib is mainly associated with fasting hypoglycaemia and hepatomegaly. Most GSD Ib patients also show neutropenia and neutrophil dysfunction and therefore are at risk of developing severe infections and inflammatory bowel disease (IBD). An increased risk for autoimmune disorders, such as thyroid autoimmunity and Crohn-like disease, has also been demonstrated, but no systematic study on the prevalence of autoimmune disorders in GSD Ib patients has ever been performed. We describe a 25-year-old patient affected by GSD Ib who developed 'seronegative' myasthenia gravis (MG), presenting with bilateral eyelid ptosis, diplopia, dysarthria, severe dysphagia, dyspnoea and fatigue. The repetitive stimulation of peripheral nerves test showed signs of exhaustion of neuromuscular transmission, particularly evident in the cranial area. Even in the absence of identifiable anti-acetylcholine receptor antibodies, seronegative MG is considered an autoimmune disorder and may be related to the disturbed immune function observed in GSD Ib patients.

[A 35-year-old man with gynaecomastia as the first symptom of hyperthyroidism].

PubMed

Mullens, A; van den Bruel, A; Vanderschueren, D

2002-02-02

A 35-year-old man suffered painful bilateral gynaecomastia for 2 months due to serious Graves' hyperthyroidism. During treatment with propylthiouracil and levothyroxine, the plasma concentrations of thyroid hormone, sex hormones and sex hormone-binding globulin normalised and the gynaecomastia disappeared. Gynaecomastia occurs in 30 to 40% of men diagnosed with Graves' hyperthyroidism. However, gynaecomastia as a presenting symptom of this autoimmune disease is uncommon.

[Thyroid echogeneity as a useful tool for the differential diagnosis of hyperthyroidism in the course of Graves disease and Hashimoto thyroiditis].

PubMed

Niedziela, M; Warzywoda, M; Korman, E

2000-01-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) constitute a spectrum of autoimmune thyroid diseases (AITD). They share an autoimmune pathogenesis, with a cellular and a humoral response to the thyroid gland. As a consequence, dysfunction of the gland itself may develop, characterized by hyperfunction in the case of GD and hypofunction in the case of HT, however at the onset of HT the hyperthyroidism might be observed as a result of a rapid destruction of thyrocytes. An abnormal thyroid echographic pattern characterized by a diffuse low echogeneity has been described in both AITD. This hypoechogeneity is due to three components: increase of intrathyroidal flow, functional changes in thyroid follicles with increased cellularity and decrease of the colloid content, resulting in the reduction of the cell/colloid interface, variable degree of lymphocytic infiltration. The first two components may be reversible during medical treatment and seem to be characteristic for GD, whereas lymphocytic infiltration may rather represent mostly HT. Here we present a 17-year-old girl with typical clinical signs of hyperthyroidism [firm goiter (II degrees), tachycardia, palpitations, nervousness, excessive sweating and tremor]. Laboratory tests were the following: fT3 - 6.59 pg/ml(increasing), fT4 - 1.99 ng/dl(increasing), TSH - 0.02 micro IU/ml(decreasing); anti-Tg-Ab - 840 IU/ml(increasing), anti-TPO-Ab - 190 IU/ml(increasing) (4 months later antithyroid antibodies were 2200 and 70, respectively). Ultrasound examination showed hypoechogeneity of the whole gland and enhanced vascular flow based on power Doppler analysis. Thyroid scan visualized the generally increased uptake of technetium. The girl was put on beta-blocker (propranolol) and later an antithyroid drug (thiamazole) was added. A course of disease was unstable, therefore the fine-needle aspiration biopsy was performed and showed the presence of single groups of normal thyrocytes and scanty colloid with no features of HT. Power Doppler analysis showed still enhanced blood flow within a gland inspite of euthyroid state. After a very unsteady period of the disease, the euthyroid state is maintained although the medical treatment was given up. The full recovery of normal blood flow and normal echogeneity of the thyroid was documented. The latter supports the diagnosis of GD. Follow-up of the thyroid echogeneity is of great diagnostic and prognostic value if the assay of TSHR-Ab is not available. On the other side, it has to be remembered that TSHR-Ab do not have to be positive in patients with GD and can be positive in patients with HT.

Does vitamin D play a role in autoimmune endocrine disorders? A proof of concept.

PubMed

Altieri, Barbara; Muscogiuri, Giovanna; Barrea, Luigi; Mathieu, Chantal; Vallone, Carla V; Mascitelli, Luca; Bizzaro, Giorgia; Altieri, Vincenzo M; Tirabassi, Giacomo; Balercia, Giancarlo; Savastano, Silvia; Bizzaro, Nicola; Ronchi, Cristina L; Colao, Annamaria; Pontecorvi, Alfredo; Della Casa, Silvia

2017-09-01

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.

Prevalence of coeliac disease in Italian patients affected by Addison's disease.

PubMed

Biagi, Federico; Campanella, Jonia; Soriani, Alessandra; Vailati, Alberto; Corazza, Gino R

2006-03-01

It is well known that coeliac disease is associated with autoimmune endocrine diseases, such as autoimmune thyroid disease and insulin-dependent diabetes mellitus. Recently, coeliac disease has been shown in approximately 10% of patients with autoimmune Addison's disease. Addison's disease is the most common cause of primary adrenocortical insufficiency and it shares several clinical features with coeliac disease. Although hyperpigmentation and hypotension are the most specific signs, gastrointestinal symptoms are common and can be the first complaints of the patients. The aim of our study was to investigate the prevalence of coeliac disease in Italian patients with Addison's disease. Seventeen consecutive patients affected by Addison's disease (14 F, mean age 53.9 years, range 26-79 years) were enrolled in the study. Eleven of them were affected by Addison's disease associated with autoimmune thyroid disease and/or insulin-dependent diabetes mellitus; the other 6 patients were suffering from isolated Addison's disease. Diagnosis had been performed at the age of 40.5 years (range 23-55). Steroid treatment had already been started in 16 of the patients. Endomysial antibodies were tested in all of them and a duodenal biopsy was taken in those found to be positive for antiendomysial antibody (EMA). One out of 17 patients was found to be EMA positive. Duodenal biopsy confirmed the diagnosis of coeliac disease by showing subtotal villous atrophy. Although we studied only a small sample, our preliminary results confirmed that Addison's disease is associated with coeliac disease, being present in 5.9% of patients with Addison's disease. Since the symptoms can be similar and treatment of Addison's disease can mask coeliac disease, this association should always be actively investigated.

Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae

PubMed Central

Brown, Rebecca J.; Rother, Kristina I.; Artman, Henry; Mercurio, Mary Gail; Wang, Roger; Looney, R. John; Cowen, Edward W.

2010-01-01

Background Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjögren syndrome A, and anti-Smith antibodies. Conclusions Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. PMID:19153345

Hashimoto thyroiditis: clinical and diagnostic criteria.

PubMed

Caturegli, P; De Remigis, A; Rose, N R

2014-01-01

Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women. In addition to this classic form, several other clinico-pathologic entities are now included under the term HT: fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, and painless thyroiditis (sporadic or post-partum). All forms are characterized pathologically by the infiltration of hematopoietic mononuclear cells, mainly lymphocytes, in the interstitium among the thyroid follicles, although specific features can be recognized in each variant. Thyroid cells undergo atrophy or transform into a bolder type of follicular cell rich in mitochondria called Hürthle cell. Most HT forms ultimately evolve into hypothyroidism, although at presentation patients can be euthyroid or even hyperthyroid. The diagnosis of HT relies on the demonstration of circulating antibodies to thyroid antigens (mainly thyroperoxidase and thyroglobulin) and reduced echogenicity on thyroid sonogram in a patient with proper clinical features. The treatment remains symptomatic and based on the administration of synthetic thyroid hormones to correct the hypothyroidism as needed. Surgery is performed when the goiter is large enough to cause significant compression of the surrounding cervical structures, or when some areas of the thyroid gland mimic the features of a nodule whose cytology cannot be ascertained as benign. HT remains a complex and ever expanding disease of unknown pathogenesis that awaits prevention or novel forms of treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults.

PubMed

de Carvalho, Gisah Amaral; Paz-Filho, Gilberto; Mesa Junior, Cleo; Graf, Hans

2018-06-01

Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. The standard treatment of primary and central hypothyroidism is hormone replacement therapy with levothyroxine sodium (LT4). Treatment guidelines of hypothyroidism recommend monotherapy with LT4 due to its efficacy, long-term experience, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life and low cost. Despite being easily treatable with a daily dose of LT4, many patients remain hypothyroid due to malabsorption syndromes, autoimmune gastritis, pancreatic and liver disorders, drug interactions, polymorphisms in DIO2 (iodothyronine deiodinase 2), high fiber diet, and more frequently, non-compliance to LT4 therapy. Compliance to levothyroxine treatment in hypothyroidism is compromised by daily and fasting schedule. Many adult patients remain hypothyroid due to all the above mentioned and many attempts to improve levothyroxine therapy compliance and absorption have been made. © 2018 European Society of Endocrinology.

The Lipid Parameters and Lipoprotein(a) Excess in Hashimoto Thyroiditis.

PubMed

Yetkin, D O; Dogantekin, B

2015-01-01

Objective. The risk of atherosclerotic heart disease is increased in autoimmune thyroiditis, although the reason is not clear. Lipoprotein(a) (Lp(a)) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. The aim of this study is to investigate the relationship between Lp(a) levels and thyroid hormones in Hashimoto patients. Method. 154 premenopausal female Hashimoto patients (48 patients with overthypothyroid (OH), 50 patients with subclinical hypothyroid (SH), and 56 patients with euthyroid Hashimoto to (EH)) were enrolled in this study. The control group consists of 50 age matched volunteers. In every group, thyroid function tests and lipid parameters with Lp(a) were measured. Lp(a) excess was defined as Lp(a) > 30 mg/dL. Results. Total-C, LDL-C, TG, and Lp(a) levels were increased in Hashimoto group. Total-C, LDL-C, and TG levels were higher in SH group than in the control group. Total-C and LDL-C levels were also higher in EH group compared to controls. Lp(a) levels were similar in SH and EH groups with controls. However, excess Lp(a) was more common in subclinical hypothyroid and euthyroid Hashimoto group than in the control group. Conclusion. The Total-C and LDL-C levels and excess Lp(a) were higher even in euthyroid Hashimoto patients. Thyroid autoimmunity may have some effect on Lp(a) and lipid metabolism.

The Lipid Parameters and Lipoprotein(a) Excess in Hashimoto Thyroiditis

PubMed Central

Yetkin, D. O.; Dogantekin, B.

2015-01-01

Objective. The risk of atherosclerotic heart disease is increased in autoimmune thyroiditis, although the reason is not clear. Lipoprotein(a) (Lp(a)) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. The aim of this study is to investigate the relationship between Lp(a) levels and thyroid hormones in Hashimoto patients. Method. 154 premenopausal female Hashimoto patients (48 patients with overthypothyroid (OH), 50 patients with subclinical hypothyroid (SH), and 56 patients with euthyroid Hashimoto to (EH)) were enrolled in this study. The control group consists of 50 age matched volunteers. In every group, thyroid function tests and lipid parameters with Lp(a) were measured. Lp(a) excess was defined as Lp(a) > 30 mg/dL. Results. Total-C, LDL-C, TG, and Lp(a) levels were increased in Hashimoto group. Total-C, LDL-C, and TG levels were higher in SH group than in the control group. Total-C and LDL-C levels were also higher in EH group compared to controls. Lp(a) levels were similar in SH and EH groups with controls. However, excess Lp(a) was more common in subclinical hypothyroid and euthyroid Hashimoto group than in the control group. Conclusion. The Total-C and LDL-C levels and excess Lp(a) were higher even in euthyroid Hashimoto patients. Thyroid autoimmunity may have some effect on Lp(a) and lipid metabolism. PMID:26064115

The relation between gestational thyroid parameters and depression: a reflection of the downregulation of the immune system during pregnancy?

PubMed

Pop, Victor J; Wijnen, Hennie A; Lapkienne, Laima; Bunivicius, Robert; Vader, Huib L; Essed, Gerard G

2006-05-01

To assess the relation between thyroid parameters and an episode of major depression at different trimesters during pregnancy, taking into account possible confounders. Prospective follow-up of 1017 pregnant women from the general population with assessment of thyroid parameters and depression using syndromal diagnosis interviews at 12, 24, and 36 weeks' gestation. The prevalence of major depression decreased from 5.3% to 2.9%, and that of elevated concentrations of thyroid peroxidase antibody (TPOAb) titers from 8.4% to 6.5% toward the end of term. Subclinical hyperthyroidism not related to TPO-Ab (odds ration [OR] 3.6; 95% confidence interval [CI]: 1.2-0.2) and TPO-Ab (OR 2.1; 95% CI: 1.1-5.8) at 12 weeks' gestation, and TPO-Ab (OR 2.8; 95% CI 1.9-7.1) at 24 weeks' gestation were independently related to major depression. Anxiety and the occurrence of stressful life events were related to depression at all trimesters. The occurrence of major depression and high titers of TPO-Ab show a similar pattern of decline throughout pregnancy. During early gestation, thyroid autoimmunity seems to be related to depression while at the end of term-when there is maximal downregulation of the immune system-autoimmunity does not seem to play an important role with regard to the occurrence of depression.

Evaluation of Xerostomia and salivary flow rate in Hashimoto's Thyroiditis.

PubMed

Agha-Hosseini, Farzaneh; Shirzad, Nooshin; Moosavi, Mahdieh-Sadat

2016-01-01

One of the most common causes of hypothyroidism is Hashimoto's Thyroiditis (HT). Early detection of dry mouth is critical in preserving and promoting systemic and oral health. In this study we have assessed, for the first time, salivary function and xerostomia in HT patients who have not been involved with Sjögren's syndrome. HT was diagnosed in 40 patients based on clinical findings and positive anti-thyroid peroxidase antibodies (anti-TPO). Controls, matched by sex, age and body mass index (BMI), and with no history of thyroid disease, were selected. A questionnaire was used for diagnosis of xerostomia. Saliva samples were taken between 8 a.m. and 9 a.m., and at least 2 hours after the last intake of food or drink. The flow rate was calculated in milliliters per minute. Xerostomia was significantly higher in patients with HT. Unstimulated salivary flow rate was significantly lower in the HT group. Stimulated salivary flow rate was lower in HT group, but the difference was not significant. The patients with HT experienced xerostomia, and their salivary flow rate was diminished. Spitting the saliva then assessing salivary flow rate based on milliliter per minute is non-invasive, fast, and simple for chair-side diagnosis of dry mouth. Autoimmune diseases can be accompanied by salivary gland dysfunction. This may be due to the effect of cytokines in the autoimmune process or because of thyroid hormone dysfunctions.

Parity and 11-Year Serum Thyrotropin and Thyroid Autoantibody Change: A Longitudinal Population-Based Study.

PubMed

Bjergved, Lena; Carlé, Allan; Jørgensen, Torben; Perrild, Hans; Laurberg, Peter; Krejbjerg, Anne; Ovesen, Lars; Bülow Pedersen, Inge; Rasmussen, Lone Banke; Knudsen, Nils

2016-02-01

A role for female reproductive factors in the pathogenesis of thyroid autoimmunity has been suggested. This study investigated the prospective association between parity, abortion, use of oral contraceptive pill (OCP), and use of hormone replacement therapy (HRT), and 11-year change in serum thyrotropin (TSH), as well as change in thyroid peroxidase autoantibody (TPOAb) status. A random sample of 4649 people aged 18-65 years participated in a population-based study in the period 1997-1998. In the study presented here, 1749 non-pregnant women with no history of thyroid disease were included who participated in the 11-year follow-up examination in the period 2008-2010. Gynecological exposures were reported in a self-administered questionnaire at baseline and follow-up. TSH and TPOAb were measured at baseline and follow-up. Increased TPOAb status during follow-up was defined as a TPOAb below the assay cutoff (<30 kIU/L) at baseline and a TPOAb ≥30 kIU/L at follow-up. Multiple linear regression models were used, adjusted for age, smoking status, and urinary iodine excretion. An inverse association was found between the number of years on HRT and the risk (odds ratio) of increased TPOAb status during follow-up (0.735 [confidence interval 0.558-0.968], p = 0.03). However, this association was not statistically significant when applying the Bonferroni adjusted significance level. The remaining reproductive factors showed no statistically significant association with risk of increased TPOAb during follow-up. Furthermore, parity, abortions, use of OCP, HRT use, age at menarche, and being pre- or postmenopausal were not significantly associated with 11-year TSH change. No statistically significant association was found between the studied female reproductive measures and 11-year risk of TSH or TPO change. A possible protective role for HRT in the etiology of thyroid autoimmunity, however, deserves further research.

Loss-of-function mutations in the thyrotropin receptor gene as a major determinant of hyperthyrotropinemia in a consanguineous community.

PubMed

Tenenbaum-Rakover, Yardena; Grasberger, Helmut; Mamanasiri, Sunee; Ringkananont, Usanee; Montanelli, Lucia; Barkoff, Marla S; Dahood, Ahmad Mahameed-Hag; Refetoff, Samuel

2009-05-01

Resistance to TSH (RTSH) is a condition of impaired responsiveness of the thyroid gland to TSH, characterized by elevated serum TSH, low or normal thyroid hormone levels, and hypoplastic or normal-sized thyroid gland. The aim of the study was to evaluate the clinical course and the genotype-phenotype relationship of RTSH caused by two different TSH receptor (TSHR) gene mutations in a consanguineous population. We conducted a clinical and genetic investigation of 46 members of an extended family and 163 individuals living in the same town. In vitro functional studies of the mutant TSHRs were also performed. Two TSHR gene mutations (P68S and L653V) were identified in 33 subjects occurring as homozygous L653V (five subjects), heterozygous L653V (20 subjects), heterozygous P68S (four subjects), and compound heterozygous L653V/P68S (four subjects). With the exception of one individual with concomitant autoimmune thyroid disease, all homozygotes and compound heterozygotes presented with compensated RTSH (high TSH with free T(4) and T(3) in the normal range). Only nine of 24 heterozygotes had mild hyperthyrotropinemia. The L653V mutation resulted in a higher serum TSH concentration and showed a more severe in vitro abnormality than P68S. Haplotype analysis predicted a founder of the L653V six to seven generations earlier, whereas the P68S is older. Cross-sectional and prospective longitudinal studies indicate that TSH and T(4) concentrations remain stable over time. High frequency hyperthyrotropinemia in an Israeli Arab-Muslim consanguineous community is attributed to two inactivating TSHR gene mutations. Concordant genotype-phenotype was demonstrated clinically and by in vitro functional analysis. Retrospective and prospective studies indicate that in the absence of concomitant autoimmune thyroid disease, elevated TSH levels reflect stable compensated RTSH.

Hashimoto Thyroiditis and Nephrocalcinosis in a Child with Down Syndrome

PubMed Central

Spahiu, Lidvana; Jashari, Haki; Mulliqi-Kotori, Vjosa; Elezi-Rugova, Blerta; Merovci, Besart

2016-01-01

Introduction: Hypothyroidism has been reported to affect renal function and structure. However, the association of hypothyroidism with distal renal tubular acidosis (dRTA) is rarely reported in children. Case Presentation: We present a 6-year-boy with Down syndrome admitted in our department due to vomiting, weakness, polyuria, polydipsia, irritability and weight loss in the last few weeks. Investigations revealed features of hypokalemia, metabolic acidosis and alkaline urine consistent with dTRA. Abdominal ultrasound found nephrocalcinosis. In addition, Antithyroid peroxidase antibodies were positive, suggesting an autoimmune background for the pathogenesis of the tubular dysfunction. Treatment for dRTA and hypothyroidism was started and symptomatic improve was noticed. Conclusion: dRTA should be excluded in children with autoimmune disorders who develop weakness, polyuria, polydipsia or growth failure. Early diagnosis would reduce long-term complications. PMID:27147809

Hashimoto's encephalitis associated with AMPAR2 antibodies: a case report.

PubMed

Zhu, Mingqin; Yu, Xuefan; Liu, Caiyun; Duan, Chenchen; Li, Chunxiao; Zhu, Jie; Zhang, Ying

2017-02-21

Hashimoto's encephalitis (HE) is a rare neurological complication of Hashimoto's thyroiditis (HT), while limbic encephalitis (LE) is an autoimmune inflammatory disorder frequently associated with anti-neuronal antibodies. The glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) is important for synaptic transmission, memory, and learning. The etiology of HE remains unclear. We present a case of HE with antibodies to AMPAR2 both in the serum and cerebrospinal fluid. The patient presented with progressive memory loss and subsequently went into a coma. Magnetic resonance imaging revealed temporal lobe and hippocampal lesions, while the electrocardiogram showed paroxysmal delta waves. Elevated serum levels of antibodies against thyroid globulin, thyroid peroxidase, and thyroid stimulating receptor were also noted. Ultrasonography showed enlargement of the thyroid gland. Therefore, the diagnosis was established as HE. Both the CSF and serum samples of the patient tested positive for antibodies to the cell-surface antigen AMPAR2. Intravenous injection of immunoglobulin followed by dexamethasone treatment resulted in recovery from the coma. Follow-up examination three months later showed some improvement of memory. To our knowledge, this is the first report on the detection of AMPAR2 antibodies in HE. Our findings suggest that antibodies to AMPAR2 may be involved in the pathogenesis of HE. Elevated levels of thyroid antibodies possibly cause immune dysfunction, leading to the production of anti-AMPAR2 antibodies that are detrimental to the neurons. We believe that encephalitis patients with thyroid abnormalities should undergo screening for anti-neuronal antibodies, and early immune therapy may improve prognosis.

[Grave's disease in 2009].

PubMed

Philippe, Jacques

2009-04-08

Grave's disease is an autoimmune disease of the thyroid gland characterized by hyperthyroidism, a homogenous goiter and occasionally an ophtalmopathy. It occurs in less than 1% of the population with a large predominance in women (10/1). Treatment is directed to inhibit thyroid hormone synthesis with carbimazole during 12-18 months. Recurrence rates after stopping treatment is about 50%; in these patients, radioactive iodine is the preferred treatment.

Prevalence and Pattern of Autoimmune Conditions in Patients with Marginal Zone Lymphoma: A Single Institution Experience.

PubMed

Dasanu, Constantin A; Bockorny, Bruno; Grabska, Joanna; Codreanu, Ion

2015-04-01

Increased risk of B-cell non-Hodgkin lymphoma (NHL) in patients with autoimmune diseases is a known fact. An association may exist between marginal zone lymphoma (MZL) and certain autoimmune conditions and vice-versa. Herein, we present the analysis of a series of consecutive patients (n = 24) diagnosed with MZL at our institution between 2008-2014. Our series, analyzed both retrospectively and prospectively, consisted of a blend of nodal, extranodal and splenic MZL. The median age was 71.8 years; M/F ratio was 2:1. The presence of autoimmune conditions was compared to their documented prevalence in the general population and tested for statistical significance using both chi-square test (χ2) and Fisher test for small number of observations (95% confidence). A P-value < 0.05 was considered significant. A total of 50% of MZL patients had documented autoimmune conditions. In addition, 3 of 24 patients presented with more than one autoimmune disease. Statistically significant differences in our MZL patients were recorded for immune thrombocytopenia [ITP] (P < 0.01), autoimmune hemolytic anemia [AIHA] (P < 0.01), Hashimoto thyroiditis (P = 0.037) and rheumatoid arthritis [RA] (P = 0.021). The difference did not reach statistical significance for systemic lupus erythematosus (SLE) and psoriasis. ITP and AIHA in our cohort were synchronous with MZL diagnosis in all patients, while all non-hematologic autoimmune conditions were metachronous and diagnosed prior to MZL. In the course of caring for patients with MZL, a number of associated autoimmune disorders are recognized. Knowing these entities is important not only for making a correct diagnosis, but also for being able to recognize certain clinical events occurring during the course of the disease. A catalogue of autoimmune disorders associated with this type of NHL is important as they can pose formidable clinical problems for the MZL patients and their physicians.

Autoimmune thyroid disease in pregnancy: a review.

PubMed

Galofre, Juan C; Davies, Terry F

2009-11-01

The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%-15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T(4)) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L.

Autoimmune Thyroid Disease in Pregnancy: A Review

PubMed Central

Galofre, Juan C.

2009-01-01

Abstract The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%–15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T4) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L. PMID:19951221

A review on hyperthyroidism: thyrotoxicosis under surveillance.

PubMed

Mansourian, Azad Reza

2010-11-15

Thyrotoxicosis exhibit collective clinical manifestation, caused by excessive serum thyroid hormones particularity thyroxin. The clinical signs and symptoms included general alteration of metabolic process leading to weight loss fatigue and weakness and some specific disorders such as cardiovascular, neuromuscular reproductive gastrointestinal dermatological and bone disorders. The diagnosis of thyrotoxicosis relay on the thyroid function test carried out by the laboratory serum measurement of thyroxin, triiodothyronine and thyroid stimulating hormones accompanied by other para-medical examinations suggested by clinicians and endociologicst. In thyrotoxicosis serum level of thyroid hormones and thyroxin in particular elevated accompanied by pituitary thyroid stimulating hormone suppression reaching to undetectable level in sever thyrotoxicosis. Among the most common cause of thyrotoxicosis are, thyroid autoimmunity diseases thyroid toxic, adenoma toxic nodular and multinodular hyperthyroidism. The main aim behind this review is to explore the clinical manifestation, the causative factors, diagnosis, metabolic disorder occur due to thyrotoxicosis.

mRNA-Seq Reveals Novel Molecular Mechanisms and a Robust Fingerprint in Graves' Disease

PubMed Central

Sachidanandam, Ravi; Morshed, Syed; Latif, Rauf; Shi, Ruijin; Davies, Terry F.

2014-01-01

Context: The immune response in autoimmune thyroid disease has been shown to occur primarily within the thyroid gland in which the most abundant antigens can be found. A variety of capture molecules are known to be expressed by thyroid epithelial cells and serve to attract and help retain an intrathyroidal immune infiltrate. Objective: To explore the entire repertoire of expressed genes in human thyroid tissue, we have deep sequenced the transcriptome (referred to as mRNA-Seq). Design and Patients: We applied mRNA-Seq to thyroid tissue from nine patients with Graves' disease subjected to total thyroidectomy and compared the data with 12 samples of normal thyroid tissue obtained from patients having a thyroid nodule removed. The expression for each gene was calculated from the sequencing data by taking the median of the coverage across the length of the gene. The expression levels were quantile normalized and a gene signature was derived from these. Results: On comparison of expression levels in tissues derived from Graves' patients and controls, there was clear evidence for overexpression of the antigen presentation pathway consisting of HLA and associated genes. We also found a robust disease signature and discovered active innate and adaptive immune signaling networks. Conclusions: These data reveal an active immune defense system in Graves' disease, which involves novel molecular mechanisms in its pathogenesis and development. PMID:24971664

Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase.

PubMed Central

Seto, P; Hirayu, H; Magnusson, R P; Gestautas, J; Portmann, L; DeGroot, L J; Rapoport, B

1987-01-01

The thyroid microsomal antigen (MSA) in autoimmune thyroid disease is a protein of approximately 107 kD. We screened a human thyroid cDNA library constructed in the expression vector lambda gt11 with anti-107-kD monoclonal antibodies. Of five clones obtained, the recombinant beta-galactosidase fusion protein from one clone (PM-5) was confirmed to react with the monoclonal antiserum. The complementary DNA (cDNA) insert from PM-5 (0.8 kb) was used as a probe on Northern blot analysis to estimate the size of the mRNA coding for the MSA. The 2.9-kb messenger RNA (mRNA) species observed was the same size as that coding for human thyroid peroxidase (TPO). The probe did not bind to human liver mRNA, indicating the thyroid-specific nature of the PM-5-related mRNA. The nucleotide sequence of PM-5 (842 bp) was determined and consisted of a single open reading frame. Comparison of the nucleotide sequence of PM-5 with that presently available for pig TPO indicates 84% homology. In conclusion, a cDNA clone representing part of the microsomal antigen has been isolated. Sequence homology with porcine TPO, as well as identity in the size of the mRNA species for both the microsomal antigen and TPO, indicate that the microsomal antigen is, at least in part, TPO. Images PMID:3654979

The Prevalence of Thyroid Dysfunction in Elderly Cardiology Patients with Mild Excessive Iodine Intake in the Urban Area of São Paulo

PubMed Central

Duarte, Glaucia C.; Tomimori, Eduardo K.; Camargo, Rosalinda Y. A.; Rubio, Ileana G.S.; Wajngarten, Mauricio; Rodrigues, Amanda G.; Knobel, Meyer; Medeiros-Neto, Geraldo

2009-01-01

OBJECTIVES: To evaluate the prevalence of thyroid dysfunction in elderly cardiac patients in an outpatient setting. SUBJECTS AND METHODS: A total of 399 consecutive patients (268 women, age range 60–92 years) who were followed at Heart Institute were evaluated for thyroid dysfunction with serum free T4, TSH, anti-Peroxidase antibodies, urinary iodine excretion measurements and thyroid ultrasound. RESULTS: Hyperthyroidism (overt and subclinical) was present in 29 patients (6.5%), whereas hypothyroidism (overt and subclinical) was found in 32 individuals (8.1%). Cysts were detected in 11 patients (2.8%), single nodules were detected in 102 (25.6%), and multinodular goiters were detected in 34 (8.5%). Hashimoto’s thyroiditis was present in 16.8% patients, most of whom were women (83.6%). The serum TSH increased with age and was significantly higher (p= <0.01) in patients, compared to the normal control group. No significant differences in serum TSH and free T4 values were observed when patients with atrial fibrillation (AF) where compared with those without arrhythmia. The median urinary iodine levels were 210 μg/L (40–856 μg/L), and iodine levels were higher in men than in women (p<0.01). Excessive iodine intake (urinary iodine >300 μg/L) was observed in one-third of patients (30.8%). CONCLUSIONS: Elderly patients have a higher prevalence of both hypo- and hyperthyroidism as well as thyroid nodules when compared with the general population. About one-third of the older patients had elevated urinary secretion of iodine and a higher prevalence of chronic Hashimoto’s thyroiditis. It is recommended that ultrasonographic studies, tests for thyroid function and autoimmunity should be evaluated in elderly patients. PMID:19219319

Female Infertility and Serum Auto-antibodies: a Systematic Review.

PubMed

Deroux, Alban; Dumestre-Perard, Chantal; Dunand-Faure, Camille; Bouillet, Laurence; Hoffmann, Pascale

2017-08-01

On average, 10 % of infertile couples have unexplained infertility. Auto-immune disease (systemic lupus erythematosus, anti-phospholipid syndrome) accounts for a part of these cases. In the last 20 years, aspecific auto-immunity, defined as positivity of auto-antibodies in blood sample without clinical or biological criteria for defined diseases, has been evoked in a subpopulation of infertile women. A systematic review was performed (PUBMED) using the MESH search terms "infertility" and "auto-immunity" or "reproductive technique" or "assisted reproduction" or "in vitro fertilization" and "auto-immunity." We retained clinical and physiopathological studies that were applicable to the clinician in assuming joint management of both infertility associated with serum auto-antibodies in women. Thyroid auto-immunity which affects thyroid function could be a cause of infertility; even in euthyroidia, the presence of anti-thyroperoxydase antibodies and/or thyroglobulin are related to infertility. The presence of anti-phospholipid (APL) and/or anti-nuclear (ANA) antibodies seems to be more frequent in the population of infertile women; serum auto-antibodies are associated with early ovarian failure, itself responsible for fertility disorders. However, there exist few publications on this topic. The methods of dosage, as well as the clinical criteria of unexplained infertility deserve to be standardized to allow a precise response to the question of the role of serum auto-antibodies in these women. The direct pathogenesis of this auto-immunity is unknown, but therapeutic immunomodulators, prescribed on a case-by-case basis, could favor pregnancy even in cases of unexplained primary or secondary infertility.

Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice

PubMed Central

Lesage, Sylvie; Collin, Roxanne; Banuelos, Bianca; Aliesky, Holly A.; Rapoport, Basil

2017-01-01

Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the major histocompatibility class (MHC) molecule I-Ak from B10.A(4R) mice to nonobese diabetic (NOD) mice. Apart from I-Ak, the genes responsible for the NOD.H2h4 phenotype are unknown. Extending serendipitous observations from crossing BALB/c to NOD.H2h4 mice, thyroid autoimmunity was investigated in both genders of the F1, F2, and the second-generation backcross of F1 to NOD.H2h4 (N2). Medium-density linkage analysis was performed on thyroid autoimmunity traits in F2 and N2 progeny. TgAb develop before TPOAb and were measured after 8 and 16 weeks of iodide exposure; TPOAb and thyroiditis were studied at 16 weeks. TgAb, TPOAb, and thyroiditis, absent in BALB/c and F1 mice, developed in most NOD.H2h4 and in more N2 than F2 progeny. No linkages were observed in F2 progeny, probably because of the small number of autoantibody-positive mice. In N2 progeny (equal numbers of males and females), a chromosome 17 locus is linked to thyroiditis and TgAb and is suggestively linked to TPOAb. This locus includes MHC region genes from B10.A(4R) mice (such as I-Ak and Tnf, the latter involved in thyrocyte apoptosis) and genes from NOD mice such as Satb1, which most likely plays a role in immune tolerance. In conclusion, MHC and non-MHC genes, encoded within the chromosome 17 locus from both B10.A(4R) and NOD strains, are most likely responsible for the Hashimoto disease–like phenotype of NOD.H2h4 mice. PMID:28323998

Selenoproteins in human body: focus on thyroid pathophysiology.

PubMed

Valea, Ana; Georgescu, Carmen Emanuela

2018-06-05

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Unexplained hepatitis following halothane.

PubMed Central

Walton, B; Simpson, B R; Strunin, L; Doniach, D; Perrin, J; Appleyard, A J

1976-01-01

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur. PMID:1268612

Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease

PubMed Central

Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

2016-01-01

Graves’ disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus–pituitary–thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus–pituitary–thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies. PMID:26787873

Hypothyroid Graves' disease complicated with elephantiasis nostras verrucosa (ENV): a case report and review of the literature.

PubMed

Ukinç, Kubilay; Bayraktar, Miyase; Gedik, Arzu

2009-08-01

Thyroid dermopathy is not a frequent feature of hyperthyroid Graves' disease, being present in less than 5% of the patients. Graves' disease has been shown to exist in euthyroid or hypothyroid forms in untreated patients. Here, we describe a case of hypothyroid Graves' disease with elephantiasis nostras verrucosa (ENV), which is an extreme form of thyroid dermopathy (TD). A 58-year-old female patient was admitted to the emergency department with somnolence, hypothermia, and bradycardia. Her mental status gradually worsened, resulting in a deep coma. She was intubated and followed in the intensive care unit, as she needed mechanical ventilatory assistance due to respiratory failure. She also had bilateral non-pitting edema, a cobblestone-like appearance, and hyperkeratotic greenish-brown-colored lesions in the pretibial and dorsal regions of the feet that were compatible with ENV. Hypothyroid Graves' disease is a very rare condition among autoimmune thyroid disorders, and ENV is an extremely rare form of TD. Here, we present a patient with hypothyroid Graves' disease and ENV.

Thyroid nodule management: clinical, ultrasound and cytopathological parameters for predicting malignancy

PubMed Central

Maia, Frederico F. R.; Zantut-Wittmann, Denise Engelbrecht

2012-01-01

Although fine-needle aspiration cytology is considered to be the reference method for evaluating thyroid nodules, the results are inaccurate in approximately 10-30% of cases. Several studies have attempted to predict the risk of malignancy in thyroid nodules based on age, nodularity, thyrotropin values, thyroid autoimmune disease, hot/cold nodule status, and ultrasound parameters. However, no consensus has been found, and none of these parameters has significantly affected patient management. The management of indeterminate thyroid nodules and re-biopsies of nodules with initially benign cytological results remain important and controversial topics of discussion. The Bethesda cytological system and several studies on the use of molecular markers to predict malignancy from cytological samples of thyroid nodules need further clarification. More in-depth discussions among and continuous education of the specialists involved in treating thyroid disease are necessary to improve the management of these patients. This review aims to examine the clinical, laboratory, ultrasound, and scintigraphic parameters that can be used for thyroid nodule management. PMID:22948464

Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease.

PubMed

Thomas, Dimitrios; Karachaliou, Feneli; Kallergi, Konstantina; Vlachopapadopoulou, Elpis; Antonaki, Georgia; Chatzimarkou, Fotini; Fotinou, Aspasia; Kaldrymides, Philippos; Michalacos, Stefanos

2008-04-01

Elevated titers of antibodies against different herpes virus antigens have been reported in some immunodeficient and systemic autoimmune disorders. To examine if Herpes Simplex Virus (HSV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) IgG and IgM antibodies are detected more frequently in children with autoimmune thyroid disease (AITD) compared to controls. Thirty-four children with AITD, aged 9.62 +/- 2.35 years, and 31 matched controls, aged 9.24 +/- 2.98 years, were studied. The percentage of EBV IgG+ children with AITD was statistically higher than the percentage of EBV IgG+ controls (82.35% versus 51.61%, P = 0.008). The percentage of EBV IgG+ children with AITD and hypothyroidism was statistically higher than the percentage of EBV IgG+ children with AITD, without hypothyroidism (100% versus 70%, P = 0.024). No other statistically significant differences were observed in HSV-1+2, and CMV IgG or IgM antibodies between the subgroups of children studied. EBV seroprevalence is higher in children with AITD compared to controls and the underlying pathology remains to be elucidated.

Viruses and thyroiditis: an update

PubMed Central

Desailloud, Rachel; Hober, Didier

2009-01-01

Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment. PMID:19138419

Endocrinology Update: Thyroid Disorders.

PubMed

Kelley, Scott

2016-12-01

Thyroid disease affects nearly every organ system in the body. Hypothyroidism is a state of thyroid hormone insufficiency that results in decreased metabolism and secondary effects including fatigue and weight gain. Primary hypothyroidism typically is a result of autoimmune thyroiditis or iodine deficiency and is assessed by measurement of the thyroid-stimulating hormone (TSH) level. This level usually is elevated in patients with hypothyroidism and low in patients with hyperthyroidism. Levothyroxine is the treatment of choice for hypothyroidism. Hyperthyroidism is a state of thyroid hormone excess, which increases the metabolic rate and causes symptoms including anxiety and tremor. Graves disease is the most common etiology in developed countries. Patients with hyperthyroidism are evaluated with measurement of TSH and free thyroxine levels. Management options include antithyroid drugs, radioactive iodine, and surgery. Thyroid nodules are detected commonly in family medicine, and may or may not be associated with thyroid hormone abnormalities. Patients with thyroid nodules should be evaluated with TSH level measurement and thyroid ultrasonography to guide further testing. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Frequency of autoimmune diseases in myasthenia gravis: a systematic review.

PubMed

Mao, Zhi-Feng; Yang, Long-Xiu; Mo, Xue-An; Qin, Chao; Lai, Yong-Rong; He, Ning-Yu; Li, Tong; Hackett, Maree L

2011-03-01

The course of myasthenia gravis (MG) may get complicated by the development of other autoimmune diseases. Estimates of the frequency of autoimmune diseases will help inform patients and physicians, direct health policy discussion, provide etiologic clues, and optimize the management of MG. However, the frequency of autoimmune diseases in people with MG is still uncertain. A systematic search for English language studies was conducted by MEDLINE and EMBASE from 1960 through 2010. Incidence studies and case series of all MG subtypes with information about autoimmune diseases were included; 25 studies met the inclusion criteria. Although there was considerable heterogeneity, the pooled estimate of the coexisting autoimmune diseases in MG was 13% (95% confidence interval, 12%-14%). Autoimmune thyroid disease seems to occur more frequently than other autoimmune conditions in MG patients. Heterogeneity in study estimates could be explained by ascertainment bias and case mix. Furthermore, autoimmune diseases occurred significantly more often in females and anti-acetylcholine receptor seropositive MG patients. Patients with MG have an increased frequency of coexisting autoimmune diseases. Autoimmune diseases seem to occur more often in female and seropositive MG patients. Further research is needed to expand our understanding of these associations.

Immunologic Endocrine Disorders

PubMed Central

Michels, Aaron W.; Eisenbarth, George S.

2010-01-01

Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

Coexistence of autoimmune polyglandular syndrome type 2 and diabetes insipidus in pregnancy.

PubMed

Krysiak, Robert; Samborek, Malgorzata

2011-11-01

Autoimmune polyglandular syndromes are rarely diagnosed conditions characterized by the association of at least 2 organ-specific autoimmune disorders. Very few cases of these syndromes have been described during pregnancy. The authors report a case of a patient diagnosed with autoimmune thyroiditis and a history of HELLP (hemolysis, elevated liver enzymes and low platelet) syndrome in a prior pregnancy. After increasing the levothyroxine dose, she developed Addisonian crisis. Normalization of adrenal cortex function resulted in the appearance of diabetes insipidus. This report shows that pregnancy may influence the course of preexisting endocrine disorders and lead to their unmasking. Although the risk of the development of autoimmune polyglandular syndromes during pregnancy is small, they may pose a serious health problem. The possible presence of these clinical entities should be considered in every woman with 1 or more endocrine disturbances.

Correlation between sonography and antibody activity in patients with Hashimoto thyroiditis.

PubMed

Willms, Arnulf; Bieler, Dan; Wieler, Helmut; Willms, Diana; Kaiser, Klaus P; Schwab, Robert

2013-11-01

Patients with Hashimoto thyroiditis show structural changes of the thyroid that can be identified by a variety of sonographic criteria. We conducted this study to investigate whether there is a correlation between sonography and antibody activity and to assess the role of sonography in the diagnosis and follow-up of Hashimoto thyroiditis. In addition, we present a new classification system (termed the VESINC system [volume, echogenicity, sonographic texture, pseudonodular hypoechoic infiltration, nodules, and cysts]), which helps improve the clarity of sonographic findings. The study included 223 consecutive patients with previously diagnosed Hashimoto autoimmune thyroiditis who attended the thyroid clinic of the German Armed Forces Central Hospital in Koblenz for follow-up examinations between 2006 and 2008. Laboratory tests were performed to measure the levels of free triiodothyronine, free thyroxine, thyrotropin, anti-thyroglobulin antibodies (TgAbs), and antithyroid peroxidase antibodies (TPOAbs). Sonography was performed according to a strict protocol. We then assessed whether a correlation existed between antibody activity and the 6 sonographic variables of the VESINC system. Hypoechogenicity, heterogeneity, and pseudonodular hypoechoic infiltration were associated with significantly higher TPOAb activity (P < .001). There were no significant correlations between the other sonographic variables examined (cysts, nodules, and volume) or the biometric data with the TPOAb and TgAb levels. In addition, an assessment of TgAb levels did not show significant differences in correlations with any of the sonographic variables. Sonography is a noninvasive diagnostic imaging modality that provides information about the level of inflammatory activity. Markedly decreased echogenicity, heterogeneity, and multifocal pseudoinodular hypoechoic infiltration are indicative of a high level of inflammatory activity. The sonographic classification system presented here (VESINC system) can be a useful tool for comparing sonographic findings in a rapid and objective manner during follow-up of Hashimoto thyroiditis.

Management of Subclinical Hypothyroidism in Pregnancy: A Comment from the Italian Society of Endocrinology and the Italian Thyroid Association to the 2017 American Thyroid Association Guidelines-"The Italian Way".

PubMed

Rotondi, Mario; Chiovato, Luca; Pacini, Furio; Bartalena, Luigi; Vitti, Paolo

2018-05-01

The 2017 American Thyroid Association guidelines for the diagnosis and management of thyroid disease during pregnancy and the postpartum were published six years after the previous ones. They provide comprehensive clinical recommendations for the whole spectrum of thyroid diseases, as well as for optimal iodine intake during pregnancy, postpartum, and lactation. The present position statement mainly regards the recommended flow chart for therapeutic decision making in pregnant women being diagnosed with subclinical hypothyroidism. Here, we comment on the major biochemical and clinical situations and the corresponding therapeutic recommendations. In particular, we welcome the critical revision of the thyrotropin (TSH) reference range in pregnancy, and we agree that there is no need to treat thyroid peroxidase antibody-negative women with a serum TSH ranging from 2.5 μIU/mL to the upper limit of the reference range. This recommendation will hopefully reduce the huge proportion of healthy pregnant women in whom, according to the previous guidelines, levothyroxine therapy had to be initiated. On the other hand, we are concerned with the recommendation to only "consider treatment" in thyroid peroxidase antibody-negative pregnant women with a serum TSH ranging from the upper limit of the reference range to 10.0 μIU/mL. This is because thyroid antibodies may be falsely negative during gestation, and serum negative chronic autoimmune thyroiditis is a well-known clinical entity even outside pregnancy. Based on these and other arguments, we recommend treatment with levothyroxine in pregnant women with TSH levels ranging between the upper limit of the reference range and 10.0 μIU/mL independently from their thyroid antibody status.

Autoimmune endocrinopathy associated with diabetes insipidus

PubMed Central

Bhan, G. L.; O'Brien, T. D.

1982-01-01

A case is described in which diabetes insipidus was associated with hypopituitarism, insulin-independent diabetes mellitus, pernicious anaemia and circulating antibodies to the thyroid gland, adrenal gland and the pancreatic islet cells. PMID:7100039

AUTOIMMUNE DISORDERS IN WOMEN WITH TURNER SYNDROME AND WOMEN WITH KARYOTYPICALLY NORMAL PRIMARY OVARIAN INSUFFICIENCY

PubMed Central

Bakalov, Vladimir K.; Gutin, Liat; Cheng, Clara M; Zhou, Jian; Sheth, Puja; Shah, Kavita; Arepalli, Sruthi; Vanderhoof, Vien; Nelson, Lawrence M.; Bondy, Carolyn A.

2012-01-01

The higher prevalence of autoimmune diseases in women compared to men could be due to effects of ovarian hormones, pregnancy and/or the presence of a 2nd X chromosome. To elucidate the role of these factors, we investigated the prevalence and spectrum of autoimmune diagnoses in women with primary ovarian insufficiency associated with X chromosome monosomy (Turner syndrome, TS, n=244) and women with karyotypically normal (46,XX) primary ovarian insufficiency (POI, n=457) in a prospective study, conducted at the National Institutes of Health. We compared the study group prevalence to normative data for the U.S. population of women. Chronic lymphocytic (Hashimoto’s) thyroiditis (HT) occurred in 37% of women with TS vs. 15% with POI (P<0.0001); HT prevalence in both ovarian insufficiency groups significantly exceeded that in U.S. population of women (5.8%). Inflammatory bowel (IBD, 4%) and celiac disease (CD, 2.7%) were significantly increased in TS, but not in POI. No other autoimmune diagnosis, including Graves’ disease or Type 1 diabetes appears to be significantly increased in either group. Women with TS had higher pro-inflammatory IL6 and TGF β1 levels (p<0.0001 for both), and lower anti-inflammatory IL10 and TGF β2 levels (p<0.005 for both) compared to POI and to normal volunteers. Lifetime estrogen exposure and parity were significantly lower in TS compared to POI, which were in turn lower than the general population of women. The finding that lymphocytic thyroiditis is greatly increased in both women with TS and POI suggests that factors associated with ovarian insufficiency per se promote this form of autoimmunity. The absence of a normal second X-chromosome further contributes to increased autoimmunity in TS. PMID:22342295

Preclinical models of Graves' disease and associated secondary complications.

PubMed

Moshkelgosha, Sajad; So, Po-Wah; Diaz-Cano, Salvador; Banga, J Paul

2015-01-01

Autoimmune thyroid disease is the most common organ-specific autoimmune disorder which consists of two opposing clinical syndromes, Hashimoto's thyroiditis and Graves' (hyperthyroidism) disease. Graves' disease is characterized by goiter, hyperthyroidism, and the orbital complication known as Graves' orbitopathy (GO), or thyroid eye disease. The hyperthyroidism in Graves' disease is caused by stimulation of function of thyrotropin hormone receptor (TSHR), resulting from the production of agonist antibodies to the receptor. A variety of induced mouse models of Graves' disease have been developed over the past two decades, with some reproducible models leading to high disease incidence of autoimmune hyperthyroidism. However, none of the models show any signs of the orbital manifestation of GO. We have recently developed an experimental mouse model of GO induced by immunization of the plasmid encoded ligand binding domain of human TSHR cDNA by close field electroporation that recapitulates the orbital pathology in GO. As in human GO patients, immune mice with hyperthyroid or hypothyroid disease induced by anti-TSHR antibodies exhibited orbital pathology and chemosis, characterized by inflammation of orbital muscles and extensive adipogenesis leading to expansion of the orbital retrobulbar space. Magnetic resonance imaging of the head region in immune mice showed a significant expansion of the orbital space, concurrent with proptosis. This review discusses the different strategies for developing mouse models in Graves' disease, with a particular focus on GO. Furthermore, it outlines how this new model will facilitate molecular investigations into pathophysiology of the orbital disease and evaluation of new therapeutic interventions.

Evaluation of Serum S100A8/S100A9 Levels in Patients with Autoimmune Thyroid Diseases.

PubMed

Korkmaz, Hakan; Tabur, Suzan; Savaş, Esen; Özkaya, Mesut; Aksoy, Şefika Nur; Aksoy, Nurten; Akarsu, Ersin

2016-09-01

The correlation of S100A8/S100A9 with various inflammatory conditions, including autoimmune diseases have been reported. There is no study investigating the levels of S100A8/S100A9 in autoimmune thyroid diseases (AITD). We aimed to evaluate the level of serum S100A8/S100A9 in AITD. Case control study. Fifty patients with AITD (25 Hashimoto's thyroiditis (HT) and 25 Graves' disease (GD)) were included in the study. Twenty seven healthy subjects participated as a control group. Blood samples were obtained in the 3 months after the initiation of medical treatment. Serum levels of total antioxidant status (TAS), total oxidative status (TOS), total free sulfhydryl (SH), lipid hydroperoxide (LOOH) and S100A8/S100A9 were analyzed. The patients with AITD had significantly higher S100A8/S100A9, OSI, LOOH and TOS levels than the healthy control group. There was no significant difference between GD and HT patients in terms of S100A8/S100A9, TOS and OSI levels. S100A8/S100A9 level was positively correlated with LOOH, TOS and OSI levels but negatively correlated with -SH level in the patients with AITD. Serum S100A8/S100A9 levels were increased in patients with AITD and positively correlated with LOOH, TOS and OSI whereas negatively correlated with SH.

Coexistence of ulcerative colitis and Sjögren's syndrome in a patient with Takayasu's arteritis and Hashimoto's thyroiditis.

PubMed

Park, Hyun Woo; Lee, Hyun Seok; Hwang, Sejin; Lee, Han Sol; Bae, Han-Ik; Yoon, Ghilsuk

2017-04-01

A 31-year-old woman with a 15-year history of Takayasu's arteritis (TA) and a 13-year history of Hashimoto's thyroiditis presented with hematochezia. She received a diagnosis of Sjögren's syndrome at 1 month before her visit to Kyungpook National University Medical Center. Her colonoscopic findings were compatible with a diagnosis of ulcerative colitis (UC). She was treated with oral mesalazine, and her hematochezia symptoms subsequently disappeared. The coexistence of UC and TA has been reported; however, reports on the coexistence of UC and Sjögren's syndrome, or of UC and Hashimoto's thyroiditis are rare. Although the precise etiologies of these diseases are unknown, their presence together suggests that they may have a common pathophysiologic background. Furthermore, in patients with autoimmune or vascular diseases, including TA, systemic manifestations should be assessed with consideration of inflammatory bowel diseases including UC in the presence of gastrointestinal symptoms such as diarrhea and hematochezia.

Subclinical hypothyroidism: A common finding in adult patients with cyanotic congenital heart disease.

PubMed

Bak, Peter; Hjortshøj, Cristel S; Gaede, Peter; Idorn, Lars; Søndergaard, Lars; Jensen, Annette S

2018-03-01

Cyanotic congenital heart disease is a systemic disease, with effects on multiple organ systems. A high prevalence of subclinical hypothyroidism (SCH) has been reported in a small cohort of cyanotic congenital heart disease patients. Subclinical hypothyroidism has been associated with various adverse cardiovascular effects, as well as an increased risk of progression to overt hypothyroidism. The aim of this study was to examine the prevalence of SCH in cyanotic congenital heart disease patients, consider possible etiologies, and evaluate thyroid function over time. First, 90 clinically stable cyanotic congenital heart disease patients were examined with blood samples (thyroid-stimulating hormone, C-reactive protein, hemoglobin, hematocrit, and N-terminal pro-brain-natriuretic peptide) in a cross-sectional descriptive study. Second, a longitudinal follow-up study of 43 patients originating from the first study part, was carried out. These patients had thyroid function parameters (thyroid-stimulating hormone, thyroid hormones, and thyroid peroxidase antibodies) evaluated biannually. Elevated thyroid-stimulating hormone was present in 24% of the 90 screened patients. During follow-up (6.5 ± 1.0 years), SCH (defined as ≥2 consecutive elevated thyroid-stimulating hormone values) was present in 26%. Three patients progressed to overt hypothyroidism. Patients with SCH were younger (34 ± 12 vs 42 ± 16 years; P = .01) and had a lower oxygen saturation (80 ± 5 vs 84 ± 6%; P = .03). Subclinical hypothyroidism is a very common finding in cyanotic congenital heart disease. This is not associated with increased levels of C-reactive protein, heart failure, or autoimmunity but appears to be associated with cyanosis and age. Since the clinical impact of SCH is uncertain, further studies are needed to determine this. Regular thyroid evaluation is recommended in cyanotic congenital heart disease patients since SCH can develop to overt hypothyroidism. © 2017 Wiley Periodicals, Inc.

Coexistent findings of renal glomerular disease with Hashimoto's thyroiditis.

PubMed

Koçak, Gülay; Huddam, Bülent; Azak, Alper; Ortabozkoyun, Levent; Duranay, Murat

2012-05-01

Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disease with a female preponderance. Renal involvement in HT is not uncommon. In the present study, we aimed to define the frequency and characteristics of the glomerular diseases associated with HT and further the understanding of any common pathogenesis between HT and glomerular disease. We reviewed retrospectively 28 patients with HT who were referred to our Department because of unexplained haematuria, proteinuria or renal impairment from 2007 to 2011. Routine laboratory investigations including blood count, serum biochemistry, urinalysis and 24-h urinary protein excretion were performed on all patients. Renal biopsy was performed in 20 patients with HT, and the specimens were examined by light microscopy and immunofluorescence staining. We detected four cases of focal segmental glomerulosclerosis (FSGS), four membranous glomerulonephritis (MGN), two minimal-change disease (MCD), three immunoglobulin A nephritis (IgAN), three chronic glomerulonephritis (CGN) and one amyloidosis. In three patients, the renal biopsy findings were nonspecific. Daily urinary protein excretion and glomerular filtration rates were found to be independent of the level of thyroid hormone and thyroid-specific autoantibodies. Glomerular pathologies associated with HT are similar to those in the general population, the most common lesions being MGN, FSGS and IgA nephritis. © 2012 Blackwell Publishing Ltd.

Wernicke-Korsakoff syndrome in the course of thyrotoxicosis - a case report.

PubMed

Wierzbicka-Chmiel, Joanna; Wierzbicki, Krzysztof; Kajdaniuk, Dariusz; Sędziak, Ryszard; Marek, Bogdan

2011-01-01

Wernicke-Korsakoff syndrome (also called Wernicke's encephalopathy) is a potentially fatal, neuropsychiatric syndrome caused most frequently by thiamine deficiency. The three classic symptoms found together are confusion, ataxia and eyeball manifestations. Memory disturbances can also be symptoms. Wernicke's encephalopathy mainly results from alcohol abuse, but also from malnutrition, cancer, chronic dialysis, thyrotoxicosis and, in well-founded cases, encephalopathy associated with autoimmune thyroid disease (EAATD). The coexistence of many factors makes a proper diagnosis difficult, delays appropriate treatment and consequently reduces the chance of complete recovery. We present the case of a 53 year-old female with Wernicke's encephalopathy caused by chronic malnutrition, surgical operation, as well as thyrotoxicosis. She received treatment with intravenous thiamine administration and also anti-thyroid treatment which caused satisfactory regression of her neurological symptoms.

Helicobacter pylori and autoimmune disease: Cause or bystander

PubMed Central

Smyk, Daniel S; Koutsoumpas, Andreas L; Mytilinaiou, Maria G; Rigopoulou, Eirini I; Sakkas, Lazaros I; Bogdanos, Dimitrios P

2014-01-01

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research. PMID:24574735

Detection of erythrovirus B19 in thyroidectomy specimens from Graves' disease patients: a case-control study.

PubMed

Page, Cyril; Hoffmann, Thomas Walter; Benzerdjeb, Nassim; Duverlie, Gilles; Sevestre, Henri; Desailloud, Rachel

2013-08-01

Environmental factors, such as viruses, are thought to contribute to the development of thyroid autoimmunity. Erythrovirus B19 (EVB19) is suspected to be involved in Hashimoto's thyroiditis, but no direct evidence is available concerning the role of EVB19 infection in Graves' disease. The objective of this study was to investigate whether the presence of EVB19 is more frequent in thyroidectomy specimens of patients undergoing thyroidectomy for Graves' disease (cases) than for multinodular thyroid (controls). Serum and thyroidectomy specimens were prospectively collected from 64 patients referred for total thyroidectomy over a 5-year period (2007-2011) and were investigated retrospectively and blindly for circulating EVB19 DNA by q-PCR (Qiagen), and for EVB19 thyrocyte infection by immunochemistry (VP2-Antibody, Dako). EVB19 serology was also determined. General clinical and laboratory data were collected. Twenty patients were referred for Graves' disease and 44 patients were referred for non-autoimmune multinodular thyroid. Patients with thyroid cancer were excluded. Ten percent of Graves' disease patients and 27.7% of control patients had positive staining of thyrocytes for EVB19 antibodies (ns). EVB19-positive and EVB19-negative cases did not differ. EVB19-positive controls were older than EVB19-negative controls (mean age: 57.5 [35-74] vs. 45 [28-80] years, P=0.03) No case of acute EVB19 infection was identified. EVB19-positive serology was more frequent in controls than in Graves' disease patients (88% vs. 45%, P<0.0001). EVB19 was detected in thyrocytes, but not more frequently in Graves' disease patients than in controls. Further studies are needed to determine the role of EVB19 infection in thyroid diseases. Copyright © 2013 Wiley Periodicals, Inc.

Cardiac autonomic regulation is disturbed in children with euthyroid Hashimoto thyroiditis.

PubMed

Kilic, Ayhan; Gulgun, Mustafa; Tascilar, Mehmet Emre; Sari, Erkan; Yokusoglu, Mehmet

2012-03-01

Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common form of thyroiditis in childhood. Previous studies have found autonomic dysfunction of varying magnitude in patients with autoimmune diseases, which is considered a cardiovascular risk factor. We aimed to evaluate the heart rate variability (HRV), a measure of cardiac autonomic modulation, in children with euthyroid Hashimoto thyroiditis (eHT). The study included 32 patients with eHT (27 girls and 5 boys; mean age 11 ± 4.1 years, range 8-16; body mass index 0.47 ± 0.69 kg/m(2)), as judged by normal or minimally elevated serum TSH levels (normal range: 0.34-5.6 mIU/l) and normal levels of free thyroid hormones (FT4 and FT3) and 38 euthyroid age-matched controls. Patients with eHT and control subjects underwent physical examination and 24-hour ambulatory ECG monitoring. Time-domain parameters of HRV were evaluated for cardiac autonomic functions. Children with eHT displayed significantly lower values of time-domain parameters of SDANN (standard deviation of the averages of NN intervals), RMSSD (square root of the mean of the sum of the squares of differences between adjacent NN intervals), NN50 counts (number of pairs of adjacent NN intervals differing by more than 50 ms) and PNN50 (NN50 count divided by the total number of all NN intervals) for each 5-min interval, compared to healthy controls (p < 0.05 for each), indicating the decreased beat-to-beat variation of heart rate. In conclusion, eHT is associated with disturbed autonomic regulation of heart rate. Hence, the children with eHT are at higher risk for developing cardiovascular diseases.

Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

PubMed

Vila, L; Donnay, S; Arena, J; Arrizabalaga, J J; Pineda, J; Garcia-Fuentes, E; García-Rey, C; Marín, J L; Serra-Prat, M; Velasco, I; López-Guzmán, A; Luengo, L M; Villar, A; Muñoz, Z; Bandrés, O; Guerrero, E; Muñoz, J A; Moll, G; Vich, F; Menéndez, E; Riestra, M; Torres, Y; Beato-Víbora, P; Aguirre, M; Santiago, P; Aranda, J; Gutiérrez-Repiso, C

2016-05-01

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 μg/l, and 17·9 % of children showed UI<100 μg/l. The median UI was higher in males (180·8 v. 153·6 μg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis.

PubMed

Collet, Tinh-Hai; Bauer, Douglas C; Cappola, Anne R; Asvold, Bjørn O; Weiler, Stefan; Vittinghoff, Eric; Gussekloo, Jacobijn; Bremner, Alexandra; den Elzen, Wendy P J; Maciel, Rui M B; Vanderpump, Mark P J; Cornuz, Jacques; Dörr, Marcus; Wallaschofski, Henri; Newman, Anne B; Sgarbi, José A; Razvi, Salman; Völzke, Henry; Walsh, John P; Aujesky, Drahomir; Rodondi, Nicolas

2014-09-01

Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.

Preoperative management in patients with Graves' disease.

PubMed

Piantanida, Eliana

2017-10-01

Graves' disease is the most frequent cause of hyperthyroidism in iodine-sufficient geographical areas and is characterized by the presence in patients' serum of autoantibodies directed against the thyrotropin receptor (TRAb) that cause overproduction and release of thyroid hormones. Clinical presentation results from both hyperthyroidism and underlying autoimmunity. The diagnosis is based on characteristic clinical features and biochemical abnormalities. If serum thyrotropin (TSH) is low, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations should be measured to distinguish between subclinical (with normal circulating thyroid hormones) and overt hyperthyroidism (with increased circulating thyroid hormones). Graves' disease is treated with any of three effective and relatively safe initial treatment options: antithyroid drugs (ATDs), radioactive iodine ablation (RAIU), and surgery. Total thyroidectomy is favored in several clinical situations, such as intolerance, ineffectiveness or recurrence after ATD treatment, radioiodine therapy contraindicated, documented or suspected thyroid malignancy, one or more large thyroid nodules, coexisting moderate-to-severe active Graves' orbitopathy, women planning a pregnancy within 6 months. Whenever surgery is selected as treatment, selection of an expert high-volume thyroid surgeons is fundamental and careful preoperative management is essential to optimize surgical outcomes. Pretreatment with ATDs in order to promptly achieve the euthyroid state is recommended to avoid the risk of precipitating thyroid storm during surgery. For the majority of patients, euthyroidism is achieved after few weeks of ATD treatment. Beta-blockers, such as propranolol, are often added effectively to control hyperthyroid symptoms. Saturated solution of potassium iodide (SSKI) or potassium iodine (Lugol's solution), given for a short period prior to surgery, in order to reduce both thyroid hormone release and thyroid gland vascularity, is beneficial to decrease intra-operative blood loss.

HURTLE CELLS IMMUNOHISTOCHEMICAL ACTIVITIES IN HASHIMOTO THYROIDITIS PARENCHYMA.

PubMed

Tsagareli, Z; Kvachadze, T; Melikadze, E; Metreveli, L; Nikobadze, E; Gogiashvili, L

2016-11-01

The present study was designed to evaluate the participation and utility of Hǘrtle cells morphological requirment and transformation under Hashimoto autoimmune thyroiditis versus Riedel´s struma. Several markers have been evaluated to detect induced activities of Hǘrtle cells. Study subject - specimens (tissue fragments) collected from TG surgery (thyroidectomy) for mollecular (receptor) diagnosis of Hǘrtle cells activities using routine histological and immunohistochemical samples. 89 cases were selected in Hashimoto thyroiditis diagnosis with Hǘrtle cells history (adenoma and adenomatous grouth of oncocytes). Markers as: TSH receptors, TTF-1, S-100 protein, also anti-TPO and anti-TG levels in blood plasm were detected. It was shown that solid cell claster-nests like agregation of oncocytes and adenomatous growth foci in parafollicular areas with anti-TPO and anti-TG antibodies levels arising while Riedel´s struma shown only large intra- and extra glandular inflammatory proliferative fibrosing process. Large positive expression of TTF-1 and S-100 protein and the negative reaction of TSH receptor factor suggest that Thyroid parenchyma disorganization and mollecular biological atypia with Hǘrtle cells are proceses due to hypothyreoidismus, as well as neuroectodermal cells prominent activities in 70% of Hashimoto cases.

Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice.

PubMed

McLachlan, Sandra M; Lesage, Sylvie; Collin, Roxanne; Banuelos, Bianca; Aliesky, Holly A; Rapoport, Basil

2017-04-01

Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the major histocompatibility class (MHC) molecule I-Ak from B10.A(4R) mice to nonobese diabetic (NOD) mice. Apart from I-Ak, the genes responsible for the NOD.H2h4 phenotype are unknown. Extending serendipitous observations from crossing BALB/c to NOD.H2h4 mice, thyroid autoimmunity was investigated in both genders of the F1, F2, and the second-generation backcross of F1 to NOD.H2h4 (N2). Medium-density linkage analysis was performed on thyroid autoimmunity traits in F2 and N2 progeny. TgAb develop before TPOAb and were measured after 8 and 16 weeks of iodide exposure; TPOAb and thyroiditis were studied at 16 weeks. TgAb, TPOAb, and thyroiditis, absent in BALB/c and F1 mice, developed in most NOD.H2h4 and in more N2 than F2 progeny. No linkages were observed in F2 progeny, probably because of the small number of autoantibody-positive mice. In N2 progeny (equal numbers of males and females), a chromosome 17 locus is linked to thyroiditis and TgAb and is suggestively linked to TPOAb. This locus includes MHC region genes from B10.A(4R) mice (such as I-Ak and Tnf, the latter involved in thyrocyte apoptosis) and genes from NOD mice such as Satb1, which most likely plays a role in immune tolerance. In conclusion, MHC and non-MHC genes, encoded within the chromosome 17 locus from both B10.A(4R) and NOD strains, are most likely responsible for the Hashimoto disease-like phenotype of NOD.H2h4 mice. Copyright © 2017 Endocrine Society.

Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis.

PubMed

Bonfig, W; Gärtner, R; Schmidt, H

2010-06-01

In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations in patients with autoimmune thyroiditis (AIT). Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab) concentrations in children with AIT. Forty-nine patients (33 females) with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n=18), levothyroxine plus 100 microg sodium-selenite (group B, n=13), or levothyroxine plus 200 microg sodium-selenite (group C, n=18). Mean age at diagnosis was 12.2+/-2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6+/-0.5 microg/kg body weight to lower TSH to the treatment goal of 1-2 microU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p=0.03 and p=0.01), but not in group B (p=0.06). It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 microg daily nor given in the "adult" supplementation dose of 200 microg daily.

Hypothyroidism in patients with autoimmune pancreatitis.

PubMed

Shimizuguchi, Ryoko; Kamisawa, Terumi; Endo, Yuka; Kikuyama, Masataka; Kuruma, Sawako; Chiba, Kazuro; Tabata, Taku; Koizumi, Satomi

2018-05-06

To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis (AIP) patients. We examined thyroid function in 77 patients with type 1 AIP (50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. Eight patients (10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine (FT4) and high thyroid stimulating hormone (TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine (FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG4-related disease (IgG4-RD); presence of anti-thyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP. Hypothyroidism was observed in 8 (10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.

Immunopathogenesis of Thyroid Eye Disease: Emerging Paradigms

PubMed Central

Naik, Vibhavari M; Naik, Milind N; Goldberg, Robert A; Smith, Terry J; Douglas, Raymond S

2009-01-01

Graves disease represents a systemic autoimmune process targeting the thyroid, orbit, and pretibial skin. The thyroid dysfunction is treatable, but no consistently effective medical therapy has yet been described for the orbital manifestations of Graves disease, also known as thyroid-associated ophthalmopathy or thyroid eye disease. Several autoantigens are potentially relevant to the pathogenesis of thyroid eye disease. Activating antibodies generated against the thyrotropin receptor can be detected in a majority of patients, and these drive hyperthyroidism. However, stimulating antibodies against the insulin-like growth factor-1 receptor (IGF-1R) may also play a role in the extra-thyroid manifestations of GD. IGF-1R is over-expressed by orbital fibroblasts derived from patients with TED, while IGF-1R+ T and IGF-1R+ B cells are considerably more frequent in GD. Actions of several cytokines and the molecular interplay peculiar to the orbit appear to provoke the inflammation, fat expansion, and deposition of excessive extracellular matrix molecules in thyroid eye disease. Based upon these new insights, several therapeutic strategies can now be proposed that, for the first time, might specifically interrupt its pathogenesis. PMID:20385333

The Clinical and Thyroid Function Studies of Lymphocytic Thyroiditis with Spontaneously Resolving Hyperthyroidism: Comparison to Subacute Thyroiditis

PubMed Central

Koh, Eun Hee; Park, Yong Joon; Lee, Hyun Chul; Hong, Chein Soo; Huh, Kap Bum; Lee, Sang Yong; Ryu, Kyung Za

1986-01-01

Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH) has been reported in the past years, and is referred to as “silent thyroiditis.” It is characterized by a low or decreased radioactive iodine uptake (RAIU) of thyroid in a patient with hyperthyroidism in whom initial diagnosis is generally thought to be Graves’ disease. Thirty-five patients who had hyperthyroidism or goiter with decreased RAIU have been assessed. Twenty-four (68.6%) of 35 patients had LT-SRH and the remaining patients, subacute thyroiditis (SAT). The clinical characteristics of the patients with LT-SRH were a history of delivery, painless goiter, elevated T3 and T4 levels and positive anti-microsomal antibodies. Anti-microsomal antibodies were positive in 70.8% of the LT-SRH group, whereas 12.5% in the SAT group. Resolution of the hyperthyroidism took 8 to 12 months. It is considered that LT-SRH is an autoimmune thyroiditis with spontaneously resolving hyperthyroidism and determination of the RAIU is very useful in differentiating from other forms of hyperthyroidism. PMID:15759376

Hashimoto thyroiditis: a century later.

PubMed

Ahmed, Rania; Al-Shaikh, Safa; Akhtar, Mohammed

2012-05-01

More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized. The most recently recognized variant is immunoglobulin G4(+) HT, which may occur as isolated thyroid limited disease or as part of a generalized Ig4-related sclerosing disease. The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. HT is frequently associated with papillary thyroid carcinoma and may indeed be a risk factor for developing this type of cancer. The relationship between thyroid lymphoma and HT on the other hand appears well established.

The changing scene in Hashimoto's disease: a review.

PubMed

Stuart, Angus

2011-09-01

The review briefly describes the evolution of hypotheses about cronic thyroiditis, the escape of colloid hypothesis, basement membrane destruction, the auto-immune theory and the role of disregulatory genes. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dry Eye

MedlinePlus

... the Meibomian glands. Autoimmune disorders such as Sjögren’s syndrome, lupus, scleroderma, and rheumatoid arthritis and other disorders such as diabetes, thyroid disorders, and Vitamin A deficiency are associated with dry eye. Women are more likely to develop dry eye. ...

Tryptic peptides of canine thyroglobulin reactive with sera of patients with canine hypothyroidism caused by autoimmune thyroiditis.

PubMed

Lee, J-Y; Uzuka, Y; Tanabe, S; Takasawa, T; Sarashina, T; Nachreiner, R F

2004-10-01

Canine thyroglobulin (cTg) was treated with trypsin at a ratio of trypsin to cTg of 1:100 (w/w). Tryptic peptides of cTg were analysed by Western immunoblotting for their reactivity to serum thyroglobulin autoantibodies (TgAA) from patients with TgAA-positive hypothyroidism and normal individuals. The sera of patients with TgAA-positive hypothyroidism reacted with several peptides: 43, 32.5 and 31 kDa; the sera of normal individuals did not bind these tryptic peptides. Some of the TgAA-positive sera of patients reacted with 25 kDa peptide in addition to three tryptic peptides above. This experiment was the first report about antigenic epitopes of cTg. These small tryptic peptides recognized by TgAA may be related with the induction of TgAA and may be useful as markers for autoimmune thyroid diseases in dog.

Screening of celiac disease in patients with autoimmune thyroid disease from Southern Brazil.

PubMed

Teixeira, Laila M; Nisihara, Renato; Utiyama, Shirley Ramos da Rosa; Bem, Ricardo S de; Marcatto, Cristina; Bertolazo, Michelli; Carvalho, Gisah A de

2014-08-01

The objective of this study was to determine the prevalence of celiac disease (CD) in adults with autoimmune thyroid disease (ATD) from the endocrinology outpatient setting in a university hospital in Southern Brazil. From the years 2007 to 2011, 254 patients with ATD were enrolled consecutively, Grave's disease was diagnosed in 143 (56.3%) and Hashimoto's thyroiditis in 111 (43.7%) of them. All patients answered a questionnaire related to symptoms that could be associated with CD and serum samples to screen for IgA anti-endomysial (EmA-IgA) were collected. EmA-IgA-positive patients were offered upper gastrointestinal endoscopy and biopsy of duodenum. A total of 254 patients were included; 222 (87.4%) female, mean age 45.4 ± 13.43 years (18 to 79 years). EmA-IgA was positive in seven patients (2.7%) and five done endoscopy with biopsy. Of these, three diagnosis of CD was confirmed (1.2%). All the three patients with CD had higher EmA-IgA titration, were female and had Hashimoto's thyroiditis. Like other patients with ATD, CD patients had nonspecific gastrointestinal symptoms, such as heartburn and gastric distention. In our study, one in each 85 patients confirmed the diagnosis of CD. We found a prevalence of 1.2% (1:85) of confirmed CD among Brazilian patients with ATD. Although some IgA-EmA positive patients had Graves' disease and one was male, all three patients with confirmed CD were female and had Hashimoto's thyroiditis.

Laparoscopic Roux-en-Y gastric bypass surgery on morbidly obese patients with hypothyroidism.

PubMed

Fazylov, Rafael; Soto, Eliana; Cohen, Steve; Merola, Stephen

2008-06-01

It is well known that obesity is accompanied by changes in thyroid function. Hypothyroidism is associated with increased body weight. The aim of this study was to evaluate the operative outcomes, weight loss, and the effect of weight loss on thyroid function in morbidly obese patients with hypothyroidism who undergo laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. A retrospective review of 20 morbidly obese female patients with hypothyroidism and on thyroid replacement therapy who underwent LRYGB between January 2003 and August 2006. Mean preoperative body mass index (BMI) was 47.6 kg/m2 (range 38-58.5 kg/m2). Average patient age was 44.5 years (range 21-66 years). There was one early complication (pneumonia). Late complications included one death, three anastomotic strictures, and one small bowel obstruction. The patients were followed for a mean of 13.5 months (range 3-24 months). Their mean excess body weight loss was 13 kg (22%), 24.4 kg (39.4%), 33.2 kg (63.3%), 38.4 kg (65%), 41.7 kg (70%), and 43 kg (73%) at 1, 3, 6, 9, 12, and 24 months, respectively. Change in a mean BMI was the same regardless of the patient preoperative and postoperative thyroxine dose. Hypothyroidism resolved in 5(25%) patients, improved in 2(10%) patients, unchanged in 8(40%) patients, and worsened in 5 (25%) patients. Most of the five whose hypothyroidism worsened had thyroid autoimmune disease. Hypothyroidism appears to improve in the vast majority of morbidly obese patients who undergo LRYGB, except for those whose thyroid disease is autoimmune in nature.

Autoimmune Thyroid Disease in Rheumatoid Arthritis: A Global Perspective

PubMed Central

Cárdenas Roldán, Jorge; Amaya-Amaya, Jenny; Castellanos-de la Hoz, Juan; Giraldo-Villamil, Juliana; Montoya-Ortiz, Gladys; Cruz-Tapias, Paola; Rojas-Villarraga, Adriana; Mantilla, Rubén D.; Anaya, Juan-Manuel

2012-01-01

Objective. To determine the prevalence and impact of autoimmune thyroid disease (AITD) in patients with rheumatoid arthritis (RA). Methods. Eight-hundred patients were included. The association between AITD and RA was analyzed was analyzed by bivariate and multivariate analysis. In addition, a literature review was done focusing on geographical variations. Results. In our cohort the prevalence of AITD was 9.8% while the presence of antibodies was 37.8% for antithyroperoxidase enzyme (TPOAb) and 20.8% for antithyroglobulin protein (TgAb). The presence of type 2 diabetes, thrombosis, abnormal body mass index, and a high educational level was positively associated with AITD. The literature review disclosed a geographical variation of AITD in RA ranging from 0.5% to 27%. Autoantibody prevalence ranges from 6% to 31% for TgAb, 5% to 37% for TPOAb, and from 11.4% to 32% for the presence of either of the two. Conclusion. AITD is not uncommon in RA and should be systematically assessed since it is a risk factor for developing diabetes and cardiovascular disease. These results may help to further study the common mechanisms of autoimmune diseases, to improve patients' outcome, and to define public health policies. An international consensus to accurately diagnose AITD is warranted. PMID:23209899

Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

PubMed

Tecellioglu, Mehmet; Kamisli, Ozden; Kamisli, Suat; Yucel, Fatma Ebru; Ozcan, Cemal

2018-03-09

Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1) cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and autoimmune thyroid disease

PubMed Central

Nielsen, C H; Hegedüs, L; Rieneck, K; Moeller, A C; Leslie, R G Q; Bendtzen, K

2007-01-01

Tumour necrosis factor (TNF)-α and interferon (IFN)-γ exert detrimental effects in organ-specific autoimmune disease, while both destructive and protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5. We examined the production of these cytokines by peripheral blood mononuclear cells (PBMC) from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD) and healthy controls, upon exposure to a thyroid self-antigen, human thyroglobulin (Tg), in the presence of autologous serum. Initially, TNF-α and IL-2 were produced in all three groups, accompanied by IL-10. Release of IFN-γ, IL-4 and, notably, IL-5 ensued. Both patient groups exhibited increased TNF-α, IL-2, IFN-γ and IL-10 responses, and PBMC from HT patients secreted lower amounts of IL-5 than male, but not female, controls. Enhanced TNF-α production by HT cells also occurred in the presence of pooled normal sera, indicating a dependency on intrinsic cellular factors. Conversely, higher production of TNF-α and IL-5 occurred in the presence of autologous sera than in the presence of pooled normal sera in both patient groups, indicating a dependency on serum constituents. Complement appeared to promote the production of IL-2 and particularly IL-5, the levels of which were reduced by neutralization of complement by heat- or zymosan treatment. The production of IFN-γ and IL-2 of the three groups together correlated directly with the serum anti-Tg activity. Moreover, TNF-α, IFN-γ, IL-5 and IL-10 responses were markedly inhibited by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the uptake of autoantigens by antigen-presenting cells. PMID:17223970

Endocrinological side-effects of immune checkpoint inhibitors.

PubMed

Torino, Francesco; Corsello, Salvatore M; Salvatori, Roberto

2016-07-01

Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance. Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent. In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

Increased serum levels of interleukin-17 and transforming growth factor-β in patients with Graves’ disease

NASA Astrophysics Data System (ADS)

Elvira, D.; Nasrul, E.; Sofyan, Y.; Decroli, E.; Darwin, E.

2018-03-01

Graves’ disease (GD) is an organ-specific autoimmune disease, characterized by excessive autoantibody levels due to tolerance breakdown of thyroid-specific autoantigens. To determine the role of interleukin-17 (IL-17) and transforming growth factor-ß (TGF-β) in GD, we assessed their serum levels in patients with GD and healthy controls. Thirty patients with hyperthyroidism, goiter, and positive thyroid-stimulating hormone receptor antibody diagnosed as GD, according to the clinical diagnostic criteria for autoimmune thyroid disease. Blood samples were also from 30 healthy individuals matched for age and sex as a control. Serum levels of IL-17 and TGF-ß were by using ELISA. IL-17 and TGF-ß levels (14.43 ± 2.15 pg/mL and 10.44 ± 3.19 pg/mL, respectively) were significantly higher in patients with GD than in controls (7.07 ± 1.45 pg/mL and 4.95 ± 1.35 pg/mL, respectively). However, no correlation between IL-17 and TGF-β level in patients with GD. The elevated serum level of IL-17 and TGF-β in patients with GD reflects Th-2 predominance, which causes increasing of these pro-inflammatory cytokines.

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

PubMed Central

Misra, Madhusmita; Levitsky, Lynne L.

2015-01-01

Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

Diagnosis of pediatric hyperthyroidism: technetium 99 uptake versus thyroid stimulating immunoglobulins.

PubMed

Baskaran, Charumathi; Misra, Madhusmita; Levitsky, Lynne L

2015-01-01

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

Vitamin D status in children with Hashimoto thyroiditis.

PubMed

Camurdan, Orhun M; Döğer, Esra; Bideci, Aysun; Celik, Nurullah; Cinaz, Peyami

2012-01-01

To investigate vitamin D status in children with Hashimoto thyroiditis. The study group consisted of 78 children recently diagnosed as Hashimoto thyroiditis and 74 subjects as the control group. Parameters of calcium metabolism, thyroid function tests, and 25-hydroxyvitamin D [25(OH)D] levels were measured. Vitamin D deficiency rate was significantly higher in the Hashimoto group compared with the control subjects (73.1% vs. 17.6%, p < 0.0001). In the Hashimoto group, mean 25(OH)D levels were significantly lower compared with the control group (31.2 +/- 11.5 versus 57.9 +/- 19.7 nmol/L, p < 0.001) and was inversely correlated with the anti-thyroid peroxidase (anti-TPO) levels (r = -0.30, p = 0.007). The higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children.

Prevalence and Impact of Thyroid Disorders on Maternal Outcome in Asian-Indian Pregnant Women

PubMed Central

Nambiar, Vimal; Jagtap, Varsha S.; Sarathi, Vijaya; Lila, Anurag R.; Kamalanathan, Sadishkumar; Bandgar, Tushar R.; Menon, Padmavathy S.; Shah, Nalini S.

2011-01-01

Aims. To establish the prevalence and the effect of thyroid dysfunction on pregnancy outcomes in Asian-Indian population. Subjects and Methods. The study cohort comprised of 483 consecutive pregnant women in the first trimester attending the antenatal clinic of a tertiary center in Mumbai, India. Thyroid hormone levels and thyroid peroxidase antibody were estimated. Patients with thyroid dysfunction were assessed periodically or treated depending on the severity. Subjects were followed until delivery. Results. The prevalence of hypothyroidism, Graves' disease, gestational transient thyrotoxicosis, and thyroid autoimmunity (TAI) was 4.8% (n = 24), 0.6% (n = 3), 6.4 % (n = 31), and 12.4% (n = 60), respectively. Forty percent of the hypothyroid patients did not have any high-risk characteristics. Hypothyroidism and TAI were associated with miscarriage (P = 0.02 and P = 0.001, resp.). Conclusions. The prevalence of hypothyroidism (4.8%) and TAI (12.4%) is high. TAI and hypothyroidism were significantly associated with miscarriage. PMID:21789274

The effect of vitamin D on thyroid autoimmunity in non-lactating women with postpartum thyroiditis.

PubMed

Krysiak, R; Kowalcze, K; Okopien, B

2016-05-01

The study included 38 non-lactating l-thyroxine-treated women with postpartum thyroiditis (PPT) and 21 matched healthy postpartum women. Women with vitamin D deficiency were treated with oral vitamin D (4000 IU daily), whereas women with vitamin D insufficiency and women with normal 25-hydroxy vitamin levels were either treated with vitamin D (2000 IU daily) or left untreated. Serum hormone levels and thyroid antibody titers were measured at the beginning of the study and 3 months later. 25-hydroxy vitamin D levels were lower in women with PPT than in healthy women. Thyroid peroxidase and thyroglobulin antibody titers inversely correlated with vitamin D status. Apart from increasing serum levels of 25-hydroxy vitamin D and decreasing serum levels of parathyroid hormone, vitamin D reduced titers of thyroid peroxidase antibodies and this effect was stronger in women with vitamin D deficiency. The study's results suggest that vitamin D supplementation may bring benefits to l-thyroxine-treated women with PPT.

Hashimoto's thyroiditis could be secondary to vitiligo: the possibility of antigen crossover and oxidative stress between the two diseases.

PubMed

Gong, Qingli; Li, Xue; Gong, Qixing; Zhu, Wenyuan; Song, Guoxin; Lu, Yan

2016-05-01

Autoimmune thyroid diseases (AITDs) are often accompanied by vitiligo, and the sera of patients with vitiligo often demonstrate increased frequencies of thyroid autoantibodies. In this study, we investigated the expression of melanocyte-associated antigens in tissues from patients with Hashimoto's thyroiditis (HT) without vitiligo using immunohistochemistry. Tissues of HT without vitiligo, as well as normal thyroid tissues, were both negative for the expression of NKI/beteb, gp100, tyrosinase-related protein 1 (TRP1), HMB-45 and S100, whereas they were positive for the expression of tyrosinase-related protein 2 (TRP2), lysosome-associated membrane protein 1 (LAMP1) and CD69. Tyrosinase (TYR) was only detected in tissues of HT, and levels of LAMP1 and CD69 were higher in tissues of HT than in normal thyroid tissues (p < 0.005). These results suggest the possibility of antigen crossover and oxidative stress between vitiligo and HT that might represent an immunological basis for secondary HT associated with vitiligo.

Hyperthyroidism and Jaundice

PubMed Central

Bal, CS; Chawla, Madhavi

2010-01-01

Development of hyperbilirubinemia, concurrent or subsequent to hyperthyroidism, can be due to thyrotoxicosis per se, or due to drug treatment of hyperthyroidism. Other rare conditions: autoimmune thyroid disease, or causes unrelated to hyperthyroidism like viral hepatitis, alcohol abuse, sepsis, cholangitis, or as a side effect of certain medications. In this article, we review these causes of co-existent hyperthyroidism and jaundice. We also highlight the changes to be expected while interpreting thyroid function tests vis-a-vis liver function tests in this subgroup of patients. PMID:21713219

Vitiligo: Pathogenesis, clinical variants and treatment approaches.

PubMed

Iannella, Giannicola; Greco, Antonio; Didona, Dario; Didona, Biagio; Granata, Guido; Manno, Alessandra; Pasquariello, Benedetta; Magliulo, Giuseppe

2016-04-01

Vitiligo is a common chronic acquired disease of pigmentation whose etiology is unknown, which usually occurs with asymptomatic whitish patch or macule. Although several hypotheses have been proposed in the literature, the leading theory is still the auto-immune etiology linked to specific genetic mutations. Vitiligo can also be associated with several autoimmune diseases, including autoimmune thyroid diseases, alopecia areata, and halo nevi. Sensorineural hearing loss was reported in several vitiligo patients due to a reduction in the number of melanocytes contained in the membranous labyrinth of the inner ear. Because of its complexity, several therapeutic options are available to treat this systemic disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Risk of thyroid cancer in patients with thyroiditis: a population-based cohort study.

PubMed

Liu, Chien-Liang; Cheng, Shih-Ping; Lin, Hui-Wen; Lai, Yuen-Liang

2014-03-01

The causative relationship between autoimmune thyroiditis and thyroid cancer remains a controversial issue. The aim of this population-based study was to investigate the risk of thyroid cancer in patients with thyroiditis. From the Longitudinal Health Insurance Database 2005 (LHID2005) of Taiwan, we identified adult patients newly diagnosed with thyroiditis between 2004 and 2009 (n = 1,654). The comparison cohort (n = 8,270) included five randomly selected age- and sex-matched controls for each patient in the study cohort. All patients were followed up from the date of cohort entry until they developed thyroid cancer or to the end of 2010. Multivariate Cox regression was used to assess the risk of developing thyroid cancer. A total of 1,000 bootstrap replicates were created for internal validation. A total of 35 patients developed thyroid cancer during the study period, of whom 24 were from the thyroiditis cohort and 11 were from the comparison cohort (incidence 353 and 22 per 100,000 person-years, respectively). After adjusting for potential confounding factors, the hazard ratio (HR) for thyroid cancer in patients with thyroiditis was 13.24 (95 % CI 6.40-27.39). Excluding cancers occurring within 1 year of follow-up, the HR remained significantly increased (6.64; 95 % CI 2.35-18.75). Hypothyroidism was not an independent factor associated with the occurrence of thyroid cancer. We found an increased risk for the development of thyroid cancer after a diagnosis of thyroiditis, independent of comorbidities.

[Amiodarone-induced thyrotoxicosis].

PubMed

Bogazzi, Fausto; Tomisti, Luca; Di Bello, Vitantonio; Martino, Enio

2017-03-01

Amiodarone-induced thyroid dysfunction occurs in about 15-20% of patients under amiodarone therapy. Amiodarone-induced hypothyroidism (AIH) can develop in patients with an apparently normal thyroid gland or in those with an underlying chronic autoimmune thyroiditis. On a clinical ground, AIH is not challenging and can be easily treated with L-thyroxine therapy. Amiodarone-induced thyrotoxicosis (AIT) can occur in patients with (AIT 1) or without (AIT 2) an underlying thyroid disease. AIT 1 is a true iodine-induced hyperthyroidism occurring in patients with an underlying thyroid autonomy while AIT 2 is a drug-induced destructive thyroiditis. According to the different pathogenetic mechanism, AIT 2 is treated with glucocorticoids while AIT 1 usually responds to thionamides. Thyroidectomy should be considered when AIT represents an imminent risk for cardiac conditions, when patients require a prompt resolution of thyrotoxicosis or when they do not respond to the medical therapy. An effective collaboration between cardiologists and endocrinologists is crucial in each part of the management of AIT patients, including the evaluation of cardiological conditions with regard to thyroid hormone excess and whether, or not, it is necessary to continue amiodarone therapy.

Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves' disease, Hashimoto's thyroiditis and type 1 diabetes mellitus.

PubMed

Pani, Michael A; Regulla, Karoline; Segni, Maria; Krause, Maren; Hofmann, Stefan; Hufner, Michael; Herwig, Jurgen; Pasquino, Anna Maria; Usadel, Klaus-H; Badenhoop, Klaus

2002-06-01

The vitamin D endocrine system plays a role in the regulation of (auto)immunity and cell proliferation. Vitamin D 1alpha-hydroxylase (CYP1alpha) is one of the key enzymes regulating both systemic and tissue levels of 1,25-dihyroxyvitamin D(3) (1,25(OH)(2)D(3)). Administration of 1,25(OH)(2)D(3), whose serum levels were found to be reduced in type 1 diabetes and thyroid autoimmunity, prevents these diseases in animal models. We therefore investigated a recently reported CYP1alpha polymorphism for an association with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. Four hundred and seven Caucasian pedigrees with one offspring affected by either type 1 diabetes (209 families), Graves' disease (92 families) or Hashimoto's thyroiditis (106 families) were genotyped for a C/T polymorphism in intron 6 of the CYP1alpha gene on chromosome 12q13.1-13.3 and transmission disequilibrium testing (TDT) was performed. Subsets of affected offspring stratified for HLA-DQ haplotype were compared using chi(2) testing. There was no deviation from the expected transmission frequency in either type 1 diabetes mellitus (P=0.825), Graves' disease (P=0.909) or Hashimoto's thyroiditis (P=0.204). However, in Hashimoto's thyroiditis the CYP1alpha C allele was significantly more often transmitted to HLA-DQ2(-) patients (27 transmitted vs 14 not transmitted; TDT: P=0.042) than expected. The C allele was less often transmitted to HLA-DQ2(+) patients (9 transmitted vs 12 not transmitted; TDT: P=0.513), although the difference was not significant (chi(2) test: P=0.143). A similar difference was observed in type 1 diabetes between offspring with high and low risk HLA-DQ haplotypes (chi(2) test: P=0.095). The CYP1alpha intron 6 polymorphism appears not to be associated with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. A potential association in subsets of patients with type 1 diabetes and Hashimoto's thyroiditis should be further investigated as well as its functional implications.

Auto-antibodies and Autoimmune Disease during Treatment of Children with Chronic Hepatitis C

PubMed Central

Molleston, Jean P.; Mellman, William; Narkewicz, Michael R.; Balistreri, William F.; Gonzalez-Peralta, Regino P.; Jonas, Maureen M.; Lobritto, Steven J.; Mohan, Parvathi; Murray, Karen F.; Njoku, Dolores; Rosenthal, Philip; Barton, Bruce A.; Talor, Monica V.; Cheng, Irene; Schwarz, Kathleen B.; Haber, Barbara A.

2012-01-01

Objectives Auto-antibodies were studied in a well-characterized cohort of children with chronic hepatitis C (CHC) during treatment with PEG-IFN and ribavirin to assess the relationship to treatment and development of autoimmune disease. Methods 114 children (5–17 years), previously screened for the presence of high titer autoantibodies, were randomized to Peg-IFN with or without ribavirin. Anti-nuclear (ANA), anti-liver-kidney-microsomal (LKM), anti-thyroglobulin (TG), anti-thyroid peroxidase (TPO), insulin (IA2), anti-glutamic acid decarboxylase (GAD) antibodies were measured after trial completion using frozen sera. Results At baseline,19% had auto-antibodies: ANA (8%), LKM (4%), and GAD (4%). At 24 and 72 weeks (24 weeks after treatment completion), 23% and 26% had auto-antibodies (p=0.50, 0.48 compared to baseline). One child developed diabetes and two hypothyroidism during treatment; none developed autoimmune hepatitis. At 24 weeks, the incidence of flu-like symptoms, gastrointestinal symptoms, and headaches were 42%, 8% and 19% in those with auto-antibodies vs. 52%, 17%, and 26% in those without (p=0.18, 0.36, and 0.20, respectively). In children with negative HCV PCR at 24 weeks, there was no difference in the rate of early virologic response /sustained virologic response respectively in those with auto-antibodies 76%/69%, vs 58%/65% in those without (p=0.48). Conclusions Despite screening, we found autoantibodies commonly at baseline, during treatment for CHC and after. The presence of antibodies did not correlate with viral response, side effects, or autoimmune hepatitis. Neither screening nor archived samples assayed for thyroid and diabetes-related antibodies identified the 3 subjects who developed overt autoimmune disease, diabetes (1) and hypothyroidism (2). PMID:23439301

Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease.

PubMed

Villanueva-Ortega, E; Ahedo, B; Fonseca-Sánchez, M A; Pérez-Durán, J; Garibay-Nieto, N; Macías-Galavíz, M T; Trujillo-Cabrera, Y; García-Latorre, E; Queipo, G

2017-08-01

Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X 2  = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X 2  = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X 2  = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS. © 2017 John Wiley & Sons Ltd.

[A Patient with Probable Dementia with Lewy Bodies and Positive Autoantibodies against the Anti-NH₂-terminal of α-Enolase].

PubMed

Ikura, Takahiro; Fujishiro, Hiroshige; Takahashi, Yukitoshi; Yoneda, Makoto; Saito, Tomoyuki; Chiba, Yuhei; Kamada, Ayuko; Katsuse, Omi; Hirayasu, Yoshio

2015-07-01

Dementia with Lewy bodies (DLB) is clinically characterized by progressive dementia that is frequently accompanied by neurological and psychiatric manifestations. Hashimoto's encephalopathy (HE) is a rare autoimmune disease with neurological and psychiatric manifestations that is not well understood. However, this disease has attracted growing attention as a treatable dementia. Although autoimmune mechanisms are thought to play a pathogenic role in HE, the etiology of the disease remains unclear. Recently, it was reported that the serum in patients with HE is frequency positive for autoantibodies against the anti-NH₂-terminal of α-enolase (anti-NAE), indicating a useful serological diagnostic marker for HE. We report the case of an 81-year-old Japanese woman with probable DLB and hypothyroidism. In her serum, elevated anti-thyroid antibodies and positive autoantibodies against anti-NAE were observed. Elevated levels of anti-glutamate receptor ε2 subunit (GluRε2) antibodies were also detected in her cerebrospinal fluid. Because her clinical condition became stable after treatment with cholinesterase inhibitor, levodopa, and levothyroxine, immunotherapy was not performed. Although the relationship between autoimmunity and cognitive decline in this patient was unclear, the present observations suggest the coexistence of neurodegeneration and autoimmunity as the underlying pathogenic mechanism.

Rare acute kidney injury secondary to hypothyroidism-induced rhabdomyolysis.

PubMed

Cai, Ying; Tang, Lin

2013-01-01

Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients. We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism- induced rhabdomyolysis from January 2006 to December 2010. Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification. Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted.

Peripheral blood lymphocyte apoptosis and its relationship with thyroid function tests in adolescents with hyperthyroidism due to Graves' disease

PubMed Central

Grywalska, Ewelina; Surdacka, Agata; Tarach, Jerzy; Klatka, Janusz; Roliński, Jacek

2012-01-01

Introduction Failures in apoptotic pathways can contribute to various autoimmune diseases, including autoimmune hyperthyroidism due to Graves’ disease (GD). The aim of the present research was to assess changes in the degree of peripheral blood (PB) lymphocyte apoptosis during methimazole (MMI) treatment in the group of teenage children, and to describe its relationship with thyroid function tests. Material and methods The percentage of PB apoptotic lymphocytes, assessed by the decrease in mitochondrial transmembrane potential (CMXRos staining), was measured in 30 adolescents at the time of diagnosis and after obtaining normalization of the thyroid hormone levels. Results The percentage of apoptotic lymphocytes in previously untreated patients with GD (5.16 ±2.81%) was significantly lower (p = 0.000001) than the percentage of apoptotic cells in the same group of patients after obtaining methimazole-induced euthyroidism (10.72 ±4.66%). There was a correlation between the increase of the mean percentages of apoptotic lymphocytes and the reduction of FT4 levels (R = 0.63, p < 0.0001), as well as the reduction of TT3 levels (R = 0.95, p < 0.0001). The more signs and symptoms accompanying the diagnosis of GD, the higher was the increment of the degree of lymphocyte apoptosis observed during the MMI-treatment (R = 0.74, p < 0.0000001). The methimazole dosage correlated (R = 0.85, p < 0.0001) with the percentage of apoptotic cells. Conclusions The use of methimazole in treatment of hyperthyroidism due to GD leads to an increment of apoptotic cells in PB. Higher doses of methimazole cause a higher increase of apoptotic lymphocytes. Apoptosis induction of human PB lymphocytes seems to be one of the indicators of proper hyperthyroidism treatment. PMID:23185197

Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism

PubMed Central

Patel, Hinal; Mansuri, Mohmmad Shoab; Singh, Mala; Begum, Rasheedunnisa; Shastri, Minal; Misra, Ambikanandan

2016-01-01

Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3’UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & p<0.0001 for allele) and TG E33 (p = 0.0003 for E33TC p<0.0001 for E33CC& p<0.0001 for allele) SNPs between patients and controls. Patients had significantly decreased mRNA levels of both sCTLA4 (p = 0.0017) and flCTLA4 (p<0.0001) compared to controls. +49A/G and CT60 polymorphisms of CTLA4 were in moderate linkage disequilibrium. Logistic regression analysis indicated significant association of CT49A/G, CT60A/G and TG exon 33 polymorphisms with susceptibility to autoimmune hypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism. PMID:26963610

Graves' disease presenting as bi-ventricular heart failure with severe pulmonary hypertension and pre-eclampsia in pregnancy--a case report and review of the literature.

PubMed

Sabah, Khandker Mohammad Nurus; Chowdhury, Abdul Wadud; Islam, Mohammad Shahidul; Cader, Fathima Aaysha; Kawser, Shamima; Hosen, Md Imam; Saleh, Mohammed Abaye Deen; Alam, Md Shariful; Chowdhury, Mohammad Monjurul Kader; Tabassum, Humayara

2014-11-18

Graves' disease, a well-known cause of hyperthyroidism, is an autoimmune disease with multi-system involvement. More prevalent among young women, it appears as an uncommon cardiovascular complication during pregnancy, posing a diagnostic challenge, largely owing to difficulty in detecting the complication, as a result of a low index of suspicion of Graves' disease presenting during pregnancy. Globally, cardiovascular disease is an important factor for pregnancy-related morbidity and mortality. Here, we report a case of Graves' disease detected for the first time in pregnancy, in a patient presenting with bi- ventricular heart failure, severe pulmonary hypertension and pre- eclampsia. Emphasis is placed on the spectrum of clinical presentations of Graves' disease, and the importance of considering this thyroid disorder as a possible aetiological factor for such a presentation in pregnancy. A 30-year-old Bangladeshi-Bengali woman, in her 28th week of pregnancy presented with severe systemic hypertension, bi-ventricular heart failure and severe pulmonary hypertension with a moderately enlarged thyroid gland. She improved following the administration of high dose intravenous diuretics, and delivered a premature female baby of low birth weight per vaginally, twenty four hours later. Pre-eclampsia was diagnosed on the basis of hypertension first detected in the third trimester, 3+ oedema and mild proteinuria. Electrocardiography revealed sinus tachycardia with incomplete right bundle branch block and echocardiography showed severe pulmonary hypertension with an estimated pulmonary arterial systolic pressure of 73 mm Hg, septal and anterior wall hypokinesia with an ejection fraction of 51%, grade I mitral and tricuspid regurgitation. Thyroid function tests revealed a biochemically hyperthyroid state and positive anti- thyroid peroxidase antibodies was found. (99m)Technetium pertechnetate thyroid scans demonstrated diffuse toxic goiter as evidenced by an enlarged thyroid gland with intense radiotracer concentration all over the gland. The clinical and biochemical findings confirmed the diagnosis of Graves' disease. Graves' disease is an uncommon cause of bi-ventricular heart failure and severe pulmonary hypertension in pregnancy, and a high index of clinical suspicion is paramount to its effective diagnosis and treatment.

Polymorphisms of IKZF3 Gene and Autoimmune Thyroid Diseases: Associated with Graves' Disease but Not with Hashimoto's Thyroiditis.

PubMed

Li, Ling; Ding, Xiaolian; Wang, Xuan; Yao, Qiuming; Shao, Xiaoqing; An, Xiaofei; Yan, Ni; Jiang, Yanfei; Wang, Wen; Shi, Liangfeng; Qin, Qiu; Song, Ronghua; Zhang, Jin-An; Sun, Peilong

2018-01-01

The IKZF3 gene encodes a zinc-finger protein that plays an important role in the proliferation and differentiation of B lymphocytes. Autoimmune thyroid diseases (AITDs), mainly include Graves' disease (GD) and Hashimoto's thyroiditis (HT), are probably caused by the aberrant proliferation of B cells. The objective of this study was to explore the association between IKZF3 polymorphisms and AITDs. We examined 915 AITD patients (604 GD and 311 HT) and 814 healthy controls. IKZF3 variants (rs2941522, rs907091, rs1453559, rs12150079 and rs2872507) were tested by PCR-ligase detection reaction. It was manifested that that the minor alleles of the five loci increased susceptibility to GD (p<0.05 for rs2941522, and p<0.01 for rs907091, rs1453559, rs12150079 and rs2872507) but in HT patients, these loci showed no significant difference compared with controls. Similarly, the genotype distributions of GD patients manifested obvious differences in all these loci compared with the control group, whereas no statistical differences were observed between HT patients and controls. Furthermore, bioinformatics tools were used to analyze rs1453559, rs12150079 and rs907091. These variants were believed to be the transcription regulator. It is the first time we reported the association between the IKZF3 polymorphisms and GD, indicating that IKZF3 gene tends to bean important risk factor for the development of GD. © 2018 The Author(s). Published by S. Karger AG, Basel.

Clinical features of a new disease concept, IgG4-related thyroiditis.

PubMed

Watanabe, T; Maruyama, M; Ito, T; Fujinaga, Y; Ozaki, Y; Maruyama, M; Kodama, R; Muraki, T; Hamano, H; Arakura, N; Kadoya, M; Suzuki, S; Komatsu, M; Shimojo, H; Notohara, K; Uchida, M; Kawa, S

2013-01-01

Immunoglobulin (Ig)G4-related disease is a recently proposed systemic disorder that includes autoimmune pancreatitis (AIP), Mikulicz's disease, and various other organ lesions. In the present retrospective study, we examined whether thyroid lesions should also be included in IgG4-related disease (Ig4-RD) under the new term IgG4-related thyroiditis. We enrolled 114 patients with Ig4-RD, including 92 patients with AIP, 15 patients with Mikulicz's disease, and seven patients with IgG4-related cholangitis, and analysed clinical findings, function, serum values of activity markers, computed tomography (CT) images, and histology of the thyroid gland. Among the 22 patients (19%) in our cohort who were found to have hypothyroidism [thyroid stimulating hormone (TSH) > 4 mIU/L], 11 patients had clinical hypothyroidism [free thyroxine (FT4) < 1 ng/dL] and 11 patients had subclinical hypothyroidism (FT4 ≥ 1 ng/dL). Serum concentrations of IgG, IgG4, circulating immune complex (CIC), and β2-microglobulin (β2-MG) were significantly higher in the hypothyroidism group compared with the remaining 92 euthyroid patients, and serum C3 concentration was significantly lower. After prednisolone treatment, TSH values had decreased significantly (p = 0.005) in this group and FT4 values had increased significantly (p = 0.047). CT images showed that the thyroid glands of patients with clinical hypothyroidism had a significantly greater volume than those of the euthyroid and other groups. Pathological analysis of one resected thyroid gland disclosed a focused lesion with infiltration of lymphocytes and IgG4-bearing plasma cells and loss of thyroid follicles. Thyroid lesions associated with hypothyroidism can be considered as a new disease termed IgG4-related thyroiditis. Awareness of this condition should lead to appropriate corticosteroid treatment that may prevent progression to a fibrous state.

Autoimmune disorders in women with turner syndrome and women with karyotypically normal primary ovarian insufficiency.

PubMed

Bakalov, Vladimir K; Gutin, Liat; Cheng, Clara M; Zhou, Jian; Sheth, Puja; Shah, Kavita; Arepalli, Sruthi; Vanderhoof, Vien; Nelson, Lawrence M; Bondy, Carolyn A

2012-06-01

The higher prevalence of autoimmune diseases in women compared to men could be due to effects of ovarian hormones, pregnancy and/or the presence of a second X chromosome. To elucidate the role of these factors, we investigated the prevalence and spectrum of autoimmune diagnoses in women with primary ovarian insufficiency associated with X chromosome monosomy (Turner syndrome, TS, n = 244) and women with karyotypically normal (46,XX) primary ovarian insufficiency (POI, n = 457) in a prospective study, conducted at the National Institutes of Health. We compared the study group prevalence to normative data for the U.S. population of women. Chronic lymphocytic (Hashimoto's) thyroiditis (HT) occurred in 37% of women with TS vs. 15% with POI (P < 0.0001); HT prevalence in both ovarian insufficiency groups significantly exceeded that in U.S. population of women (5.8%). Inflammatory bowel (IBD, 4%) and celiac disease (CD, 2.7%) were significantly increased in TS, but not in POI. No other autoimmune diagnosis, including Graves' disease or Type 1 diabetes appears to be significantly increased in either group. Women with TS had higher pro-inflammatory IL6 and TGF β1 levels (p < 0.0001 for both), and lower anti-inflammatory IL10 and TGF β2 levels (p < 0.005 for both) compared to POI and to normal volunteers. Lifetime estrogen exposure and parity were significantly lower in TS compared to POI, which were in turn lower than the general population of women. The finding that lymphocytic thyroiditis is greatly increased in both women with TS and POI suggests that factors associated with ovarian insufficiency per se promote this form of autoimmunity. The absence of a normal second X-chromosome further contributes to increased autoimmunity in TS. Published by Elsevier Ltd.

Altered balance between self-reactive T helper (Th)17 cells and Th10 cells and between full-length forkhead box protein 3 (FoxP3) and FoxP3 splice variants in Hashimoto's thyroiditis.

PubMed

Kristensen, B; Hegedüs, L; Madsen, H O; Smith, T J; Nielsen, C H

2015-04-01

T helper type 17 (Th17) cells play a pathogenic role in autoimmune disease, while interleukin (IL)-10-producing Th10 cells serve a protective role. The balance between the two subsets is regulated by the local cytokine milieu and by the relative expression of intact forkhead box protein 3 (FoxP3) compared to FoxP3Δ2, missing exon 2. Th17 and Th10 cell differentiation has usually been studied using polyclonal stimuli, and little is known about the ability of physiologically relevant self-antigens to induce Th17 or Th10 cell differentiation in autoimmune thyroid disease. We subjected mononuclear cells from healthy donors and patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) to polyclonal stimulation, or stimulation with human thyroglobulin (TG), human thyroid peroxidase (TPO), or Esherichia coli lipopolysaccharide (LPS). TPO and LPS induced increased differentiation of naive CD4(+) CD45RA(+) CD45R0(-) T cells from HT patients into Th17 cells. Th10 cell proportions were decreased in HT after polyclonal stimulation, but were comparable to those of healthy donors after antigen-specific stimulation. Taken together, our data show that an increased Th17 : Th10 ratio was found in HT patients after stimulation with thyroid-specific self-antigens. We also observed an elevated baseline production of IL-6 and transforming growth factor (TGF)-β1 and of mRNA encoding FoxP3Δ2 rather than intact FoxP3. This may contribute to the skewing towards Th17 cell responses in HT. © 2014 British Society for Immunology.

Hypothyroidism and obesity: An intriguing link.

PubMed

Sanyal, Debmalya; Raychaudhuri, Moutusi

2016-01-01

According to common perception, hypothyroidism is held responsible for obesity. However, linking them causally is controversial. Overt hypothyroidism is associated with modest weight gain, but there is a lack of clarity regarding subclinical hypothyroidism. Novel view indicates that changes in thyroid-stimulating hormone (TSH) could well be secondary to obesity. The increasing prevalence of obesity further confounds definition of normal TSH range in population studies. Thyroid autoantibody status may help in establishing the diagnosis of subclinical hypothyroidism in obesity. High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism. There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients.

Graves' disease: diagnostic and therapeutic challenges (multimedia activity).

PubMed

Kahaly, George J; Grebe, Stefan K G; Lupo, Mark A; McDonald, Nicole; Sipos, Jennifer A

2011-06-01

Graves' disease is the most common cause of hyperthyroidism in the United States. Graves' disease occurs more often in women with a female:male ratio of 5:1 and a population prevalence of 1% to 2%. A genetic determinant to the susceptibility to Graves' disease is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. Graves' disease is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid antigen-specific T cells into the thyroid and thyroid-stimulating hormone receptor expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens, such as thyroid peroxidase, thyroglobulin, and the thyroid-stimulating hormone receptor. The thyroid-stimulating hormone receptor is central to the regulation of thyroid growth and function. Stimulatory autoantibodies in Graves' disease activate the thyroid-stimulating hormone receptor leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Below-normal levels of baseline serum thyroid-stimulating hormone receptor, normal to elevated serum levels of T4, elevated serum levels of T3 and thyroid-stimulating hormone receptor autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of Graves' disease (available at: http://supplements.amjmed.com/2010/hyperthyroid/faculty.php). This Resource Center is also available through the website of The American Journal of Medicine (www.amjmed.com). Click on the “Thyroid/Graves' Disease” link in the “Resource Centers” section, found on the right side of the Journal homepage. Copyright © 2011 Elsevier Inc. All rights reserved.

Inheritable and sporadic non-autoimmune hyperthyroidism.

PubMed

Ferraz, Carolina; Paschke, Ralf

2017-03-01

Hyperthyroidism is a clinical state that results from high thyroid hormone levels which has multiple etiologies, manifestations, and potential therapies. Excluding the autoimmune Graves disease, autonomic adenomas account for the most import cause of non-autoimmune hyperthyroidism. Activating germline mutations of the TSH receptor are rare etiologies for hyperthyroidism. They can be inherited in an autosomal dominant manner (familial or hereditary, FNAH), or may occur sporadically as a de novo condition, also called: persistent sporadic congenital non-autoimmune hyperthyroidism (PSNAH). These three conditions: autonomic adenoma, FNAH and PSNAH constitute the inheritable and sporadic non-autoimmune hyperthyroidism. Particularities in epidemiology, etiology, molecular and clinical aspects of these three entities will be discussed in this review in order to guide to an accurate diagnosis allowing among others genetic counseling and presymptomatic diagnosis for the affected families. The optimal treatment based on the right diagnosis will avoid consequences of a persistent or relapsing hyperthyroidism. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Anti-PD-L1 atezolizumab-Induced Autoimmune Diabetes: a Case Report and Review of the Literature.

PubMed

Hickmott, Laura; De La Peña, Hugo; Turner, Helen; Ahmed, Fathelrahman; Protheroe, Andrew; Grossman, Ashley; Gupta, Avinash

2017-04-01

Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors trigger an immune-mediated anti-tumour response by promoting the activation of cytotoxic T lymphocytes. Although proven to be highly effective in the treatment of several malignancies they can induce significant immune-related adverse events (irAEs) including endocrinopathies, most commonly hypophysitis and thyroid dysfunction, and rarely autoimmune diabetes. Here we present the first case report of a patient with a primary diagnosis of urothelial cancer developing PD-L1 inhibitor-induced autoimmune diabetes. A euglycemic 57 year old male presented to clinic with dehydration after the fifth cycle of treatment with the novel PD-L1 inhibitor atezolizumab. Blood tests demonstrated rapid onset hyperglycaemia (BM 24 mmol/L), ketosis and a low C-peptide level (0.65 ng/mL) confirming the diagnosis of type 1 diabetes. He responded well to insulin therapy and was discharged with stable blood glucose levels. Due to the widening use of PD-1/PD-L1 inhibitors in cancer treatment clinicians need to be aware of this rare yet treatable irAE. Given the morbidity and mortality associated with undiagnosed autoimmune diabetes we recommend routine HbA1c and plasma glucose testing in all patients prior to and during treatment with PD-1/PD-L1 inhibitors until more evidence has accumulated on identifying those patients with a pre-treatment risk of such irAEs.

Non-autoimmune primary hypothyroidism in diabetic and non-diabetic chronic renal dysfunction.

PubMed

Bando, Y; Ushiogi, Y; Okafuji, K; Toya, D; Tanaka, N; Miura, S

2002-11-01

The aim of this study was to investigate the frequency and mechanisms of hypothyroidism observed in diabetic patients with advanced diabetic nephropathy, including outcomes of management for this condition. A controlled study was designed using 32 diabetic and 31 non-diabetic patients not receiving hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) who excreted mean urinary protein greater than 0.5 g/day examined on three consecutive days during admission to our hospital. Thyroid hormones in both serum and urine, anti-thyroid antibodies, renal function and iodine concentrations in serum were measured during admission in all patients included. In particular, in patients who showed overt hypothyroidism, further studies including large-needle biopsies of the thyroid and iodine-perchlorate discharge tests were performed. All patients in the two groups revealed negative antithyroid antibody titers, and the mean serum total iodine levels did not significantly differ between the two groups. Mean serum FT4 levels significantly decreased, and the TSH level was significantly elevated in the diabetic group compared to those in the non-diabetic group (p < 0.005, p < 0.02, respectively). The frequency of overt hypothyroidism in the diabetic group (22%; 7/32) was significantly higher (p < 0.05) than that in the non-diabetic group (3.2%; 1/31). The daily urinary thyroid hormone excretion in both groups did not show any significant correlation with serum thyroid hormone levels. Seven patients who revealed overt hypothyroidism in the diabetic group showed elevated serum total iodine levels during hypothyroidal status, ranging between 177 and 561 microg/l. Also, the iodine-perchlorate discharge tests carried out in six of these patients all showed a positive discharge. After management based on iodine restriction, normalization of serum thyroid hormone levels in accordance with definite decreases in the serum total iodine level was achieved, accompanied by a significant weight reduction. In conclusion, we found a significantly high prevalence of non-autoimmune primary hypothyroidism in patients with advanced diabetic nephropathy compared to those with non-diabetic chronic renal dysfunction, which may partly relate to earlier development of oedematous status. Clinical and laboratory findings suggest that impaired renal handling of iodine resulting in an elevation of serum iodine levels, rather than autoimmune mechanism or urinary hormone loss, may play a principal role in the development of these conditions, probably through a prolongation of the Wolff-Chaikoff effect. The mechanisms by which this phenomenon develops more frequently in diabetic than in non-diabetic renal dysfunction remain to be elucidated.

Stiff person syndrome: presentation of a case with repetitive complex discharges in electromiograms.

PubMed

Jiménez Caballero, Pedro Enrique

2009-07-01

Stiff person syndrome is characterized by rigidity of axial and proximal limb muscles, associated with muscle spasms, triggered by unexpected acoustic or somesthetic stimuli. It usually has an autoimmune basis, in which the blood contains antiglutamate decarboxylase antibodies, and is associated with different types of autoimmune diseases. The electromyogram provides evidences of continuous muscular activity. A 41-year-old woman with a history of diabetes mellitus type I, Hashimoto thyroiditis, vitiligo, and pernicious anemia developed symptoms compatible with stiff person syndrome. In the electromyogram, in addition to continuous muscular activity, there was evidence of complex repetitive activity in the form of doublets and triplets. Given the absence of clinical or electrophysiological neuropathic affectation, the presence of doublets and triplets in our patient could be due to a subclinical functional alteration of alpha motoneurons. They could produce the complex repetitive discharges when released from the inhibition mediated by GABAergic neurons.

Thyroid Antibody Status, Subclinical Hypothyroidism, and the Risk of Coronary Heart Disease: An Individual Participant Data Analysis

PubMed Central

Collet, Tinh-Hai; Bauer, Douglas C.; Cappola, Anne R.; Åsvold, Bjørn O.; Weiler, Stefan; Vittinghoff, Eric; Gussekloo, Jacobijn; Bremner, Alexandra; den Elzen, Wendy P. J.; Maciel, Rui M. B.; Vanderpump, Mark P. J.; Cornuz, Jacques; Dörr, Marcus; Wallaschofski, Henri; Newman, Anne B.; Sgarbi, José A.; Razvi, Salman; Völzke, Henry; Walsh, John P.; Aujesky, Drahomir

2014-01-01

Context: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk. Objective: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs). Data Sources and Study Selection: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes. Data Extraction: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events. Data Synthesis: Among 38 274 adults (median age 55 y, 63% women), 1691 (4.4%) had subclinical hypothyroidism, of whom 775 (45.8%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.87–1.53 vs HR 1.26, CI 1.01–1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87–1.56 vs HR 1.26, CI 1.02–1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status. Conclusions: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes. PMID:24915118

Iodine deficiency and thyroid disorders.

PubMed

Zimmermann, Michael B; Boelaert, Kristien

2015-04-01

Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association Studies of the GPR103 and BCL2L15 Genes in Autoimmune Thyroid Disease in the Japanese Population

PubMed Central

Ban, Yoshiyuki; Tozaki, Teruaki; Nakano, Yasuko

2016-01-01

While the past genome-wide association study (GWAS) for autoimmune thyroid diseases (AITDs) was done in Caucasians, a recent GWAS in Caucasian patients with both AITD and type 1 diabetes [a variant of autoimmune polyglandular syndrome type 3 (APS3v)] identified five non-HLA genes: BCL2L15, MAGI3, PHTF1, PTPN22, and GPR103. The aim of our study was to replicate these associations with AITD in a Japanese population. Since analyzing the rs2476601 single-nucleotide polymorphism (SNP) within the PTPN22 gene revealed no polymorphism in the Japanese, we analyzed four SNPs, rs2358994 (in BCL2L15), rs2153977 (in MAGI3), rs1111695 (in PHTF1), and rs7679475 (in GPR103) genotypes in a case–control study based on 447 Japanese AITD patients [277 Graves’ disease (GD) and 170 Hashimoto’s thyroiditis (HT) patients] and 225 matched Japanese controls using the high-resolution melting and unlabeled probe methods. Case–control association studies were performed using the χ2 and Fisher’s exact tests with Yates correction. The G allele of rs7679475 (A/G) was associated with HT compared with controls [P = 0.022, odds ratio (OR) = 0.69]. GD showed no significant associations with any SNPs. However, when patients with GD were stratified according to Graves’ ophthalmopathy (GO), the G allele of rs2358994 (A/G) was associated with GO vs. controls (P = 0.018, OR = 1.52). These findings suggest that in the Japanese population the GPR103 gene may contribute to the pathogenesis of HT. Moreover, this study demonstrated that the SNP rs2358994 within BCL2L15 gene is associated with GO in the Japanese population. PMID:27486433

Assessment of Vitamin D Level in Autoimmune Thyroiditis Patients and a Control Group in the Polish Population.

PubMed

Maciejewski, Adam; Wójcicka, Marlena; Roszak, Magdalena; Losy, Jacek; Łącka, Katarzyna

2015-01-01

Vitamin D, known for its role in calcium-phosphorus homeostasis, is also a significant immunomodulatory factor. Vitamin D deficiency has been reported in some autoimmune disorders. Recently, vitamin D level in autoimmune thyroiditis (HT - Hashimoto's thyroiditis) has become the subject of researchers' interest. This study aims to assess vitamin 25-OH-D3 levels in HT patients in comparison to a control group in the Polish population. This would be the first attempt conducted in this region with such poor sunlight exposure. The group we studied consisted of 62 subjects diagnosed with HT (mean age 49.15±15.51) and 32 healthy controls matched with age and sex (mean age 46.09±14.32). All blood samples were collected in the first quarter of the year to minimize the impact of seasonal fluctuations of vitamin D concentrations. In the HT group the mean vitamin D level was 20.09 nmol/L (SD±12.66), compared to 30.31 nmol/L (SD±19.49) in the controls, p=0.014. None of the patients and the controls was vitamin D sufficient (75-125 nmol/L). The deficiency (<50 nmol/L) was significantly more common among HT patients compared to the controls (61-98.4% vs. 27- 84.4%, p=0.029). In conclusion, we found that serum vitamin D concentration is significantly lower in HT patients in comparison to the control group. This suggests vitamin D deficit as one of the risk factors for HT development. Observed vitamin D level was also low in the control group, therefore wider supplementation in general population should be recommended.

The natural history of autoimmune Addison's disease with a non-classical presentation: a case report and review of literature.

PubMed

Manso, Jacopo; Pezzani, Raffaele; Scarpa, Riccardo; Gallo, Nicoletta; Betterle, Corrado

2018-05-24

Autoimmune Addison's disease (AAD) is the most frequent cause of adrenocortical insufficiency. The natural history of AAD usually comprises five consecutive stages with the first stage characterized by the increase of plasma renin consistent with the impairment of pars glomerulosa, which is usually the first affected layer of the adrenal cortex. We describe a 19-year-old female with Hashimoto's thyroiditis (HT) who underwent an autoantibody screening due to having the personal and family history of other autoimmune diseases in the absence of relevant clinical manifestations. She was positive for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OH Ab) at high titers. She had increased basal levels of ACTH with normal basal cortisol not responding to ACTH stimulation, reduced levels of dehydroepiandrosterone-sulfate but normal levels of orthostatic renin and aldosterone. This scenario was consistent with a subclinical AAD presenting with first impairments in pars fasciculata and reticularis and conserved pars glomerulosa function. Only subsequently, progressive deficiency in pars glomerulosa function has become evident. Review of the literature showed that there was only one case, reported to date, with a similar atypical natural history of AAD. The strategies for screening for ACA/21-OH Ab in patients with HT are discussed.

[Age characteristics of the cardiovascular system, depending on the thyroid function in type 2 diabetes mellitus].

PubMed

Ignateva, P A; Ballyuzek, M F; Shpakov, A O

To study the features of cardiovascular system in patients with diabetes mellitus type 2 considering the thyroid pathology and age, 264 patients were examined. They were divided into three groups: 1st - patients with diffuse-nodular changes in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a control group of patients without thyroid disease. The patients of different ages were examined in each of these groups. All patients were in euthyroid state. It was established that identified in diabetes mellitus type 2 thyroid pathology and the thyroid disease contribute special features to the clinical picture for combined diabetic and cardiovascular pathology even in a euthyroid state including the age features. The laboratory and instrumental researches showed that the patients with combined diabetes and thyroid pathology have a higher incidence of atrial fibrillation, ischemic heart disease, and ventricular arrhythmias of high grades. They also were noticed to have a more adverse form of the left ventricle remodeling, also the combination of diastolic and systolic dysfunctions were found to be more frequent. It was concluded about the necessity of early diagnosis and correction of the cardiovascular disorders and thyroid systems in type 2 diabetes mellitus patients, including euthyroid patients.

Hashimoto's Thyroiditis: Celebrating the Centennial Through the Lens of the Johns Hopkins Hospital Surgical Pathology Records

PubMed Central

De Remigis, Alessandra; Chuang, Kelly; Dembele, Marieme; Iwama, Akiko; Iwama, Shintaro

2013-01-01

Hashimoto's thyroiditis is now considered the most prevalent autoimmune disease, as well as the most common endocrine disorder. It was initially described in 1912, but only rarely reported until the early 1950s. To celebrate this centennial, we reviewed the surgical pathology archives of the Johns Hopkins hospital for cases of Hashimoto's thyroiditis, spanning the period from May 1889 to October 2012. Approximately 15,000 thyroidectomies were performed at this hospital over 124 years. The first surgical case was reported in 1942, 30 years after the original description. Then, 867 cases of Hashimoto's thyroiditis were seen from 1942 to 2012, representing 6% of all thyroidectomies. Hashimoto's thyroiditis was the sole pathological finding in 462 cases; it accompanied other thyroid pathologies in the remaining 405 cases. The most commonly associated pathology was papillary thyroid cancer, an association that increased significantly during the last two decades. The most common indication for thyroidectomy was a thyroid nodule that was cytologically suspicious for malignancy. Hashimoto's thyroiditis remains a widespread, intriguing, and multifaceted disease of unknown etiology one century after its description. Advances in the understanding of its pathogenesis and preoperative diagnosis will improve recognition and treatment of this disorder, and may one day lead to its prevention. PMID:23151083

Prevalence of diagnostic characteristics indicating canine autoimmune lymphocytic thyroiditis in giant schnauzer and hovawart dogs.

PubMed

Ferm, K; Björnerfeldt, S; Karlsson, A; Andersson, G; Nachreiner, R; Hedhammar, A

2009-04-01

To investigate prevalence of autoantibodies to thyroglobulin (TgAA) and/or elevated levels of thyroid stimulating hormone (TSH), indicating canine autoimmune lymphocytic thyroiditis (CLT) and/or hypothyroidism, in two high-risk dog breeds. A cohort study was conducted in two birth cohorts of giant schnauzer and hovawart dogs. The cohorts were three to four and six to seven years of age at the time of blood sampling and screening for TgAA and TSH levels. Blood sampling was accompanied by one initial and one follow-up questionnaire to the dog owners. A total number of 236 giant schnauzers and 95 hovawarts were included in the study. Seventeen (7.2 per cent) giant schnauzers and three (3.2 per cent) hovawarts had been diagnosed as hypothyroid at the time of sampling. Out of the remaining dogs, 22 giant schnauzers (10.0 per cent) and nine hovawarts (10.1 per cent) had elevated TgAA and/or TSH levels. Prevalence of elevated TgAA and TSH levels varied with age. The high prevalence of diagnostic characteristics indicating CLT/hypothyroidism in these two breeds suggests a strong genetic predisposition. It would be advisable to screen potential breeding stock for TSH and TgAA as a basis for genetic health programmes to reduce prevalence of CLT in these breeds.

Hashimoto's thyroiditis following Graves' disease.

PubMed

Umar, Husaini; Muallima, Nur; Adam, John M F; Sanusi, Harsinen

2010-01-01

Both Graves' disease and chronic thyroiditis (Hashimoto's thyroiditis) are autoimmune diseases of thyroid gland. Graves' disease is caused by stimulation of TSH receptor located on the thyroid gland by an antibody, which is known as TSH receptor antibody (TRAb). Furthermore, this may lead to hyperplasia and hyperfunction of the thyroid gland. On the contrary, the cause of Hashimoto's thyroiditis is thought due to a TSH stimulation-blocking antibody (TSBAb) which blocks the action of TSH hormone and subsequently brings damage and atrophy to thyroid gland. Approximately 15-20% of patients with Graves' disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto's disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves' disease remains unclear. It has been estimated that chronic thyroiditis or Hashimoto's disease, which occurs following the Graves' disease episode is due to extended immune response in Graves' disease. It includes the immune response to endogenous thyroid antigens, i.e. thyroid peroxidase and thyroglobulin, which may enhance lymphocyte infiltration and finally causes Hashimoto's thyroiditis. We report four cases of chronic thyroiditis (Hashimoto's disease) in patients who have been previously diagnosed with Graves' hyperthyroidism. In three cases, Hashimoto's thyroiditis occurs in 7 to 25 years after the treatment of Grave's disease; while the other case has it only after few months of Grave's disease treatment. The diagnosis of Hashimoto's disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment.

Onset of Graves' disease during pregnancy in a woman with established hypothyroidism.

PubMed

Alberiche, María; Sánchez-Hernández, Rosa María; López Mérida, Xabier; Wägner, Ana María

2017-01-01

Pregnancy strongly influences the thyroid gland and its function. Thyroid guidelines recommend a 30 to 50% increase of the preconceptional levothyroxine dose in women with hypothyroidism, when pregnancy is diagnosed. A 33 year-old, 8-week pregnant woman with hypothyroidism, presents with a 2-week history of palpitations, sweating, nervousness and fatigue. Physical examination shows tachycardia (108 bpm), distal tremors and diffuse goiter. After biochemical confirmation of hyperthyroidism, her levothyroxine dose is reduced and finally interrupted. Propylthiouracil is started and maintained until after the delivery of a healthy baby at week 40. Two weeks postpartum, hyperthyroidism worsens and propylthiouracil is replaced by methimazole. Eighteen months after delivery 7.5 mCi 131Iodine was given. Two months later, hypothyroidism developed and levothyroxine was initiated. Although conversion of Hashimoto's hypothyroidism into Graves' disease is exceptional in pregnancy, pregnant women with autoimmune hypothyroidism should ideally have their TSH concentrations measured before empirically increasing their levothyroxine dose.

[Postpartum thyroiditis. A review].

PubMed

Hurtado-Hernández, Z; Segura-Domínguez, A

2013-01-01

Postpartum thyroiditis (PPT) is a transient thyroid dysfunction of autoimmune origin that can occur in the first year postpartum in women who have not been previously diagnosed with thyroid disease. It may start with clinical thyrotoxicosis followed by hypothyroidism and the subsequent recovery of thyroid function, or may just appear as isolated thyrotoxicosis or hypothyroidism. PPT recurs in high percentage of patients after subsequent pregnancies. Many women develop permanent hypothyroidism sometime during the 3 to 10 year period after an episode of PPT. It is important for family physicians to be familiar with this disease, due to its high prevalence in order to make a correct diagnosis and therapeutic intervention. Family doctors also play a crucial role in the monitoring of these patients, given the negative implications of established hypothyroidism on reproduction in the female population during their reproductive years. This article reviews the principle characteristics of PPT along with its diagnosis and treatment. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

[Thyroid dysfunction during pregnancy].

PubMed

Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

2015-10-21

Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Thyroid epithelial cell hyperplasia in IFN-gamma deficient NOD.H-2h4 mice.

PubMed

Yu, Shiguang; Sharp, Gordon C; Braley-Mullen, Helen

2006-01-01

The role of inflammatory cells in thyroid epithelial cell (thyrocyte) hyperplasia is unknown. Here, we demonstrate that thyrocyte hyperplasia in IFN-gamma-/- NOD.H-2h4 mice has an autoimmune basis. After chronic exposure to increased dietary iodine, 60% of IFN-gamma-/- mice had severe thyrocyte hyperplasia with minimal or moderate lymphocyte infiltration, and thyroid dysfunction with reduced serum T4. All mice produced anti-thyroglobulin autoantibody. Some wild-type NOD.H-2h4 mice had isolated areas of thyrocyte hyperplasia with predominantly lymphocytic infiltration, whereas IL-4-/- and 50% of wild-type NOD.H-2h4 mice developed lymphocytic thyroiditis but no thyrocyte hyperplasia. Both thyroid infiltrating inflammatory cells and environmental factors (iodine) were required to induce thyrocyte hyperplasia. Splenocytes from IFN-gamma-/- mice with thyrocyte hyperplasia, but not splenocytes from naïve IFN-gamma-/- mice, induced hyperplasia in IFN-gamma-/- NOD.H-2h4.SCID mice. These results may provide clues for understanding the mechanisms underlying development of epithelial cell hyperplasia not only in thyroids but also in other tissues and organs.

Autoantibodies to alfa-fodrin in patients with Hashimoto thyroiditis and Sjögren's syndrome: possible markers for a common secretory disorder.

PubMed

Szanto, Antonia; Csipo, Istvan; Horvath, Ildiko; Biro, Edit; Szodoray, Peter; Zeher, Margit

2008-09-01

Presence of autoantibodies to alfa-fodrin was investigated in patients with Sjögren's syndrome (n = 61), Hashimoto thyroiditis (n = 27), Sjögren's syndrome associated with Hashimoto thyroiditis (n = 31) and in healthy persons (n = 77). In each group, level of alfa-fodrin antibodies was higher than in the controls. There was no significant difference in their presence either between patients with Hashimoto thyroiditis with or without Sjögren's syndrome, or-in IgA isotype-between Sjögren's and Hashimoto thyroiditis patients. Correlation was found between the level of IgG alfa-fodrin and anti-thyroglobulin antibodies. Based on these findings, fodrin can be associated with both endocrine and exocrine glandular secretion. Antibodies to alfa-fodrin might have a role in the pathogenesis of Hashimoto thyroiditis concerning the "final common effectory pathway", secretion. Alfa-fodrin antibodies can be good markers of secretory disorders. Assessment of these autoantibodies might help the diagnosis and follow-up of patients with impaired secretory capability of not only autoimmune origin.

Consequences of dysthyroidism on the digestive tract and viscera

PubMed Central

Daher, Ronald; Yazbeck, Thierry; Jaoude, Joe Bou; Abboud, Bassam

2009-01-01

Thyroid hormones define basal metabolism throughout the body, particularly in the intestine and viscera. Gastrointestinal manifestations of dysthyroidism are numerous and involve all portions of the tract. Thyroid hormone action on motility has been widely studied, but more complex pathophysiologic mechanisms have been indicated by some studies although these are not fully understood. Both thyroid hormone excess and deficiency can have similar digestive manifestations, such as diarrhea, although the mechanism is different in each situation. The liver is the most affected organ in both hypo- and hyperthyroidism. Specific digestive diseases may be associated with autoimmune thyroid processes, such as Hashimoto’s thyroiditis and Grave’s disease. Among them, celiac sprue and primary biliary cirrhosis are the most frequent although a clear common mechanism has never been proven. Overall, thyroid-related digestive manifestations were described decades ago but studies are still needed in order to confirm old concepts or elucidate undiscovered mechanisms. All practitioners must be aware of digestive symptoms due to dysthyroidism in order to avoid misdiagnosis of rare but potentially lethal situations. PMID:19533804

Autoimmune gastritis presenting as iron deficiency anemia in childhood.

PubMed

Gonçalves, Cristina; Oliveira, Maria Emília; Palha, Ana M; Ferrão, Anabela; Morais, Anabela; Lopes, Ana Isabel

2014-11-14

To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation. A descriptive, observational study including pediatric patients with a diagnosis of autoimmune gastritis (positive parietal cell antibody and gastric corpus atrophy) established in a 6 year period (2006-2011) in the setting of refractory iron deficiency anemia (refractoriness to oral iron therapy for at least 6 mo and requirement for intravenous iron therapy) investigation, after exclusion of other potentially contributing causes of anemia. Helicobacter pylori (H. pylori) infection and anti-secretory therapy were also excluded. Data were retrospectively collected from clinical files, including: demographic data (age, gender, and ethnic background), past medical history, gastrointestinal symptoms, familial history, laboratorial evaluation (Hb, serum ferritin, serum gastrin, pepsinogen I/ pepsinogen II, B12 vitamin, intrinsic factor autoantibodies, thyroid autoantibodies, and anti-transglutaminase antibodies), and endoscopic and histological findings (HE, Periodic Acid-Schiff/Alcian blue, gastrin, chromogranin A and immunochemistry analysis for CD3, CD20 and CD68). Descriptive statistical analysis was performed (mean, median, and standard deviation). We report a case-series concerning 3 girls and 2 boys with a mean age of 13.6 ± 2.8 years (3 Caucasian and 2 African). One girl had type I diabetes. Familial history was positive in 4/5 cases, respectively for autoimmune thyroiditis (2/5), sarcoidosis (1/5) and multiple myeloma (1/5). Laboratorial evaluation on admission included: Hb: 9.5 ± 0.7 g/dL; serum ferritin: 4.0 ± 0.9 ng/mL; serum gastrin: 393 ± 286 pg/mL; low pepsinogen I/ pepsinogen II ratio in 1/5 patients; normal vitamin B12 levels (analyzed in 3 patients). Endoscopy findings included: duodenal nodularity (2/5) and gastric fold softening (2/5), and histological evaluation showed corpus atrophic gastritis with lymphocytic infiltration (5/5), patchy oxyntic gland mononuclear cell infiltration (5/5), intestinal and/or pseudo-pyloric metaplasia in corpus mucosa (4/5), and enterochromaffin cell hyperplasia (4/5). Immunochemistry for gastrin on corpus biopsies was negative in all cases. Duodenal histology was normal. All biopsies were negative for H. pylori (Giemsa staining and cultural examination). We highlight autoimmune gastritis as a diagnosis to be considered when investigating refractory iron deficiency anemia in children, particularly in the setting of a personal/familial history of autoimmune disease, as well as the diagnostic contribution of a careful immunohistological evaluation.

Massive pericardial effusion associated with hypothyroidism.

PubMed

Ionescu, Simona Daniela; Tănase, Daniela Maria; Ouatu, Anca; Ambăruş, V; Dosa, Anca; Arsenescu-Georgescu, Cătălina

2014-01-01

The diagnosis of hypothyroidism is difficult because hypothyroidism in adults and especially the elderly, classic, has an insidious onset with a range of nonspecific symptoms which may delay diagnosis for months or even years. Old age seems to represent trigger factor for autoimmune diseases, including hypothyroidism. Clinical features in hypothyroidism, such as weight gain, fatigue, cold intolerance, constipation, dry skin, edema and muscle weakness, and decreased osteo-tendinous reflexes are usually subtle and can be overlooked. Thyroid dysfunction may be associated with a negative impact on the cardiovascular system. Pericardial, pleural and peritoneal effusions are common findings in hypothyroidism. This case report represents a typical primary hypothyroidism (autoimmune) and shows the clinical features of this disease. Basically we talked about a severe myxedema with the involvement of internal organs in an elderly woman and the euthyroidism restoration, under thyroid replacement therapy, was correlated with the clinical improvement and cardiovascular and neurological status, with radiographic remission and regression to extinction of pericardial effusion at repeated echocardiographic evaluations.

Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study.

PubMed

Kitahara, Cari M; K Rmendiné Farkas, Dóra; Jørgensen, Jens Otto L; Cronin-Fenton, Deirdre; Sørensen, Henrik Toft

2018-06-01

Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Nationwide (Denmark). Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

PubMed Central

Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W; Hoermann, Rudolf

2015-01-01

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4–T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23–29 and >29 nmol/s revealed an increasing FT3–FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3–TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases. PMID:26335522

Analysis of orbital T cells in thyroid-associated ophthalmopathy

PubMed Central

Förster, G; Otto, E; Hansen, C; Ochs, K; Kahaly, G

1998-01-01

Thyroid-associated ophthalmopathy (TAO) has a major effect on the two compartments of the retro-orbital (RO) space, leading to enlargement of the extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue is a characteristic feature of TAO and there is current interest in whether these T cells are specifically and selectively reactive to RO tissue itself. We recently established 18 T cell lines (TCL) from RO adipose/connective tissue of six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T cells reactive to autologous RO tissue protein fractions. Here we report on the phenotype characteristics and cytokine gene expression profiles of these orbital TCL and on their immunoreactivity to the organ-specific thyroid antigens thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG). Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL), interferon-gamma (IFN-γ) (n = 10), tumour necrosis factor-beta (TNF-β) (n = 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-α (n = 12) and IL-10 (n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other 16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were predominantly CD4+ there were no significant relationships between TCL phenotype, cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare) occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine gene expression in all RO tissue-reactive TCL support the concept that TAO is a tissue-specific autoimmune disease, distinct immunologically from the thyroid, and involving both T cell and B cell autoimmune mechanisms in disease pathogenesis. PMID:9649211

Fetal/Neonatal Thyrotoxicosis in a Newborn From a Hypothyroid Woman With Hashimoto Thyroiditis.

PubMed

Kiefer, Florian W; Klebermass-Schrehof, Katrin; Steiner, Manuel; Worda, Christof; Kasprian, Gregor; Diana, Tanja; Kahaly, George J; Gessl, Alois

2017-01-01

Fetal/neonatal thyrotoxicosis is a rare but potentially life-threatening condition. It is most commonly observed in poorly controlled Graves disease during pregnancy. Here we describe a fetus/newborn patient with thyrotoxicosis who was born of a woman with Hashimoto thyroiditis and levothyroxine-treated hypothyroidism. Transplacental passage of stimulating thyrotropin (TSH) receptor antibodies, which were measured by a cell-based bioassay, was the underlying mechanism of fetal/neonatal thyrotoxicosis, although the mother had no history of hyperthyroidism. Diagnosis and management of fetal hyperthyroidism can be challenging. TSH receptor antibody testing should be considered in pregnant women with any history of autoimmune thyroid disease and symptoms of fetal hyperthyroidism. Copyright © 2017 by the Endocrine Society

Thyroid-stimulation hormone-receptor antibodies as a predictor of thyrosuppressive drug therapy outcome in Graves' disease patients.

PubMed

Aleksić, Aleksandar Z; Aleksić, Željka; Manić, Saška; Mitov, Vladimir; Jolić, Aleksandar

2014-01-01

Graves' disease is autoimmune hyperthyroidism caused by pathological stimulation of thyroid-stimulation hormone-receptor antibodies. The decision on changing the therapy can be made on time by determining the prognostic factors of thyrosuppressive drug therapy outcome. The aim of the study was to determine the significance of thyroid-stimulation hormone-receptor antibodies level on the prediction of therapy outcome. The study was prospective and involved 106 drug-treated patients with newly diagnosed Graves' disease. Thyroid-stimulation hormone-receptor antibodies level was measured at the beginning of therapy, during therapy and 12 months after it had been introduced. No statistically significant difference in the level of thyroid-stimulation hormone-receptor antibodies was found at the beginning of disease and 12 months after the introduction of thyrosuppressive drug therapy among the patients who had been in remission and those who had not. Regardless of the outcome, thyroid-stimulation hormone-receptor antibodies level significantly decreased in all patients 12 months after the therapy had been introduced. The level of thyroid-stimulation hormone-receptor antibodies at the beginning of disease and 12 months after the introduction of therapy cannot predict the outcome of thyrosuppressive drug therapy.

Radiation-associated thyrotoxicosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katayama, S.; Shimaoka, K.; Osman, G.

We studied 154 consecutive patients with a diagnosis of thyrotoxicosis seen at Roswell Park Memorial Institute from 1963 to 1982. The retrospective review of the clinical materials revealed that 23 (15%) had a previous history of therapeutic radiation for various diseases. The radiation dose ranged from several to 3600 rads to the thyroid with a mean latency of 14.2 +/- 3.0 years. In 11 out of 16 patients who were tested for antithyroglobulin and antimicrosomal showed positive titers of either or both antibodies (69%). In a small number of patients, thyroid stimulating immunoglobulins were studied; long-acting thyroid stimulators (LATS) weremore » positive in one of six tested and thyrotrophin binding inhibitory immunoglobulins (TBII) in five of eight. The radiation-associated thyroidal dysfunction appears to be associated with the organ-specific autoimmune processes and could manifest as either hypo- or hyperfunction of the gland.« less

Current Concepts in Graves' Disease

PubMed Central

Girgis, Christian M.; Champion, Bernard L.; Wall, Jack R.

2011-01-01

Graves' disease is the most common cause of hyperthyroidism in the developed world. It is caused by an immune defect in genetically susceptible individuals in whom the production of unique antibodies results in thyroid hormone excess and glandular hyperplasia. When unrecognized, Graves' disease impacts negatively on quality of life and poses serious risks of psychosis, tachyarrhythmia and cardiac failure. Beyond the thyroid, Graves' disease has diverse soft-tissue effects that reflect its systemic autoimmune nature. Thyroid eye disease is the most common of these manifestations and is important to recognise given its risk to vision and potential to deteriorate in response to radioactive iodine ablation. In this review we discuss the investigation and management of Graves' disease, the recent controversy regarding the hepatotoxicity of propylthiouracil and the emergence of novel small-molecule thyroid-stimulating hormone (TSH) receptor ligands as potential targets in the treatment of Graves' disease. PMID:23148179

Modulating the function of the immune system by thyroid hormones and thyrotropin.

PubMed

Jara, Evelyn L; Muñoz-Durango, Natalia; Llanos, Carolina; Fardella, Carlos; González, Pablo A; Bueno, Susan M; Kalergis, Alexis M; Riedel, Claudia A

2017-04-01

Accumulating evidence suggests a close bidirectional communication and regulation between the neuroendocrine and immune systems. Thyroid hormones (THs) can exert responses in various immune cells, e.g., monocytes, macrophages, natural killer cells, and lymphocytes, affecting several inflammation-related processes (such as, chemotaxis, phagocytosis, reactive oxygen species generation, and cytokines production). The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions, including sepsis, inflammation, autoimmune diseases and viral infections. Under these conditions, TH therapy could contribute to restoring normal physiological functions. Here we discuss the effects of THs and thyroid stimulating hormone (TSH) on the immune system and the contribution to inflammation and pathogen clearance, as well as the consequences of thyroid pathologies over the function of the immune system. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Heritability analysis of IgG4 antibodies in autoimmune thyroid disease.

PubMed

Outschoorn, I M; Talor, M V; Burek, C L; Hoffman, W H; Rose, N R

2014-08-01

A study of IgG4 autoantibody levels in juvenile thyroid disease patients showed evidence of heritability using the ROMP screening method. These levels increased with time despite the fact that total IgG antibody decreased with time. Evidence of heritability was demonstrated only in patients with high titers of autoantibodies to both thyroglobulin (Tg) and thyroperoxidase (TPO) unlike family members who may show high titers of one or the other and be asymptomatic at the time of sampling. Since high and low IgG4 levels give different heritability plots, these findings may represent a more severe fibrotic form of thyroiditis with a distinct genetic background. Hence a simple predictive approach is offered by this screening tool for the disease in patients and family members which may be helpful in the future to identify IgG4-related thyroiditis early in the course of disease without the requirement for biopsy.

[Influence of selected endogenous and environmental factors on the course and complications of Grave's disease].

PubMed

Kurzynska, Anna; Przybylik-Mazurek, Elwira; Węgrzynowicz, Katarzyna; Morzywołek, Aleksandra; Wieczorek, Agata; Żarnowska, Maja; Hubalewska-Dydejczyk, Alicja

2014-01-01

Graves' disease (GD) is an autoimmune thyroid disease with complex and not fully established etiology. It occurs when environmental factors influence people genetically prone to this illness. The aim of this study was to determine the impact of selected factors (endogenous and environmental) on the course and complications of disease in patients with recurrent GD. Two hundred and four patients with relapsed GD, treated in the Clinical Department of Endocrinology in University Hospital in Cracow in years 2004-2006 and then in 2011 were retrospectively analyzed. Patients who agreed to participate in the study were sent questionnaire to complete. Demographic and clinical data were collected and entered into a database. Patient data included: gender, place of living, lifestyle (smoking), family history of autoimmune diseases, the course of the disease, its symptoms and the treatment strategy. Furthermore the medical documentation was analyzed. Descriptive statistical analyses were made. The study showed a significant difference in the frequency of appearance of ophthalmopathy between men and women (80% and 37.14%, respectively, p = 0.041), between smokers and nonsmokers (61.9% and 21.05%, respectively, p = 0.022) and between the age of patients with positive and negative family history of autoimmune diseases (37.6 years and 50.5 years respectively, p = 0.002). 1. Male gender is a risk factor for ophthalmopathy in GD. 2. Cigarette smoking affects the risk of Graves' ophthalmopathy. 3. A positive family history of thyroid diseases and/or autoimmune diseases promotes the development of GD at a younger age.

Chronic autoimmune disorders are increased in coeliac disease: A case-control study.

PubMed

Bibbò, Stefano; Pes, Giovanni Mario; Usai-Satta, Paolo; Salis, Roberta; Soro, Sara; Quarta Colosso, Bianca Maria; Dore, Maria Pina

2017-11-01

Coeliac disease (CD) is an autoimmune disorder of the small bowel associated with increased risk of additional autoimmune diseases (ADs).To investigate the prevalence of ADs in a population of adult coeliac patients.This was a retrospective case-control study. Data from coeliac patients and controls referred to a tertiary center between 2013 and 2016 were collected. The frequency of ADs and the unadjusted and adjusted odds ratios (ORs) for age, gender, disease duration, and body mass index with their 95% confidence intervals (CIs) were evaluated.Two hundred fifty-five patients with CD (median age 37.1 years; 206 women) were matched with 250 controls. ADs were more frequent (35.3%) in coeliac patients than in controls (15.2%). Adjusted ORs for the presence of only 1, at least 1, and more than 1 AD were 3.13 (95% CI 1.81-5.42, P < .0001), 3.31 (95% CI 2.00-5.46, P < .0001), and 3.93 (95% CI 1.49-10.36, P = .006), respectively. Hashimoto thyroiditis was the most prevalent AD (24.3% vs. 10%) OR = 2.55 (95% CI 1.39-4.70, P < .0001), followed by psoriasis (4.3% vs. 1.6%), type 1 diabetes (2.7% vs. 0.4%), and Sjögren syndrome (2.4% vs. 0.4%).These findings suggest a need for a careful surveillance of autoimmune status, especially for Hashimoto thyroiditis in patients with celiac disease. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Effects of age of onset on disease characteristics in non-segmental vitiligo.

PubMed

Solak, Berna; Dikicier, Bahar Sevimli; Cosansu, Nur C; Erdem, Teoman

2017-03-01

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non-segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid-stimulating hormone (TSH), thyroxine (T4) hormone, anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult-onset disease than in either pediatric patients or adults with childhood-onset disease (P = 0.002). Both anti-TG and anti-TPO levels were significantly higher in adults with adult-onset disease than in pediatric patients and adult patients with childhood-onset disease. The prevalence of autoimmune disease was 22.2%. Anti-TG levels were significantly higher in patients with treatment-related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo. © 2017 The International Society of Dermatology.

Few items in the thyroid-related quality of life instrument ThyPRO exhibited differential item functioning.

PubMed

Watt, Torquil; Groenvold, Mogens; Hegedüs, Laszlo; Bonnema, Steen Joop; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

2014-02-01

To evaluate the extent of differential item functioning (DIF) within the thyroid-specific quality of life patient-reported outcome measure, ThyPRO, according to sex, age, education and thyroid diagnosis. A total of 838 patients with benign thyroid diseases completed the ThyPRO questionnaire (84 five-point items, 13 scales). Uniform and nonuniform DIF were investigated using ordinal logistic regression, testing for both statistical significance and magnitude (∆R(2) > 0.02). Scale level was estimated by the sum score, after purification. Twenty instances of DIF in 17 of the 84 items were found. Eight according to diagnosis, where the goiter scale was the one most affected, possibly due to differing perceptions in patients with auto-immune thyroid diseases compared to patients with simple goiter. Eight DIFs according to age were found, of which 5 were in positively worded items, which younger patients were more likely to endorse; one according to gender: women were more likely to report crying, and three according to educational level. The vast majority of DIF had only minor influence on the scale scores (0.1-2.3 points on the 0-100 scales), but two DIF corresponded to a difference of 4.6 and 9.8, respectively. Ordinal logistic regression identified DIF in 17 of 84 items. The potential impact of this on the present scales was low, but items displaying DIF could be avoided when developing abbreviated scales, where the potential impact of DIF (due to fewer items) will be larger.

Rituximab therapy in steroid-resistant severe hypothyroid Grave's ophthalmopathy

PubMed Central

Pandit, Aditi; Gundgurthi, Abhay; Kharb, Sandeep; Brar, Karninder S.; Garg, M. K.

2013-01-01

Association of Grave's ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave's ophthalmopathy successfully treated with rituximab. PMID:23776919

Graves' hyperthyroidism and moderate alcohol consumption: evidence for disease prevention.

PubMed

Carlé, Allan; Bülow Pedersen, Inge; Knudsen, Nils; Perrild, Hans; Ovesen, Lars; Rasmussen, Lone Banke; Jørgensen, Torben; Laurberg, Peter

2013-07-01

We recently demonstrated that moderate alcohol consumption is associated with a considerable reduction in the risk of autoimmune hypothyroidism, similar to findings in other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. We aimed to study a possible association between alcohol intake and autoimmune Graves' hyperthyroidism. This is a population-based, case-control study. In a well-defined Danish population (2,027,208 person-years of observation), we prospectively identified patients with new overt thyroid dysfunction and studied 272 patients with Graves' hyperthyroidism. For each patient, we recruited four age-gender-region-matched controls with normal thyroid function (n = 1088). Participants gave detailed information on current and previous alcohol intake as well as other factors to be used for analyses. The association between alcohol intake and development of hyperthyroidism was analysed in conditional multivariate Cox regression models. Graves' patients had a lower reported alcohol consumption than controls (median units of alcohol (12 g) per week: 2 vs 4, P < 0·001). In a multivariate regression model, alcohol consumption was associated with a dose-dependent reduction in risk for development of overt Graves' hyperthyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1-2 units of alcohol per week were as follows: 0 units/week 1·73 (1·17-2·56), 3-10 units/week 0·56 (0·39-0·79), 11-20 units/week 0·37 (0·21-0·65), ≥21 units/week 0·22 (0·08-0·60). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with the type of alcohol consumed (wine vs beer), smoking habit, age, gender or region of inhabitancy. Moderate alcohol consumption is associated with a considerable reduction in the risk of Graves' disease with hyperthyroidism--irrespective of age and gender. Autoimmune thyroid disease seems to be much more dependent on environmental factors than hitherto anticipated. © 2012 John Wiley & Sons Ltd.

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression of Duox1 and the Anion Transporter Pendrin

PubMed Central

Achouri, Younes; Hahn, Stephan; Many, Marie-Christine; Craps, Julie; Refetoff, Samuel; Liao, Xiao-Hui; Dumont, Jacques E.; Van Sande, Jacqueline; Corvilain, Bernard; Miot, Françoise; De Deken, Xavier

2016-01-01

Background: The dual oxidases (Duox) are involved in hydrogen peroxide generation, which is essential for thyroid hormone synthesis, and therefore they are markers of thyroid function. During inflammation, cytokines upregulate DUOX gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates DUOX gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function. Methods: Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and ex vivo thyroid function assays. Results: Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of Duox1, Duoxa1, and the pendrin anion exchanger gene (Slc26a4) was detected. In contrast, the iodide symporter gene Slc5a5 was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected. Conclusions: This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates Duox1/Duoxa1 and Slc26a4 expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating Slc5a5 expression, while maintaining a normal euthyroid phenotype. PMID:27599561

Excess iodine promotes apoptosis of thyroid follicular epithelial cells by inducing autophagy suppression and is associated with Hashimoto thyroiditis disease.

PubMed

Xu, Chengcheng; Wu, Fei; Mao, Chaoming; Wang, Xuefeng; Zheng, Tingting; Bu, Ling; Mou, Xiao; Zhou, Yuepeng; Yuan, Guoyue; Wang, Shengjun; Xiao, Yichuan

2016-12-01

The incidence of the autoimmune thyroid disease Hashimoto thyroiditis (HT) has increased in recent years, and increasing evidence supports the contribution of excess iodine intake to thyroid disease. In this study, we examined the status of autophagy and apoptosis in thyroid tissues obtained from patients with HT, and we determined the effects of excessive iodine on the autophagy and apoptosis of thyroid follicular cells (TFCs) in an attempt to elucidate the effects of excess iodine on HT development. Our results showed decreases in the autophagy-related protein LC3B-II, and increases in caspase-3 were observed in thyroid tissues from HT patients. Interestingly, the suppression of autophagy activity in TFCs was induced by excess iodine in vitro, and this process is mediated through transforming growth factor-β1 downregulation and activation of the Akt/mTOR signaling pathway. In addition, excess iodine induced autophagy suppression and enhanced reactive oxygen species (ROS) production and apoptosis of TFCs, which could be rescued by the activation of autophagy. Taken together, our results demonstrated that excess iodine contributed to autophagy suppression and apoptosis of TFCs, which could be important factors predisposing to increased risk of HT development. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

Genetics of autoimmune thyroid disease in the Lebanese population.

PubMed

Farra, C; Awwad, J; Fadlallah, A; Sebaly, G; Hage, G; Souaid, M; Ashkar, H; Medlej, R; Gannageh, M H; Halaby, G

2012-10-01

This study aims to investigate the association of human leukocyte antigen (HLA) class II genes and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) with autoimmune thyroid diseases in the Lebanese population. A total of 128 patients with autoimmune thyroid disease (55 with Graves' disease (GD) and 73 with Hashimoto's thyroiditis (HT)) were typed for HLA DQA1 (0301 and 0501) and DQB1 (0201, 0302, and 0303) and for 49A/G CTLA-4 using PCR-based sequence-specific priming methods. A total of 186 matched controls were typed for the same alleles and compared to the diseased population. Results showed no significant differences in HLA DQB1*0201 or DQB1*0301 allelic frequencies or CTLA-4 polymorphisms between patients and controls. For GD, there was a weak association with HLA DQB1*0302 [34.6% (19 of 55) vs. 21.5% (40 of 186), P = 0.048, odds ratio (OR) = 1.926, confidence interval (CI) = 0.999-3.715] and HLA DQB1*0302-DQA1*0501 haplotype [56.36% (31 of 55) vs. 40.8% (76 of 186), P = 0.042, OR = 1.870, CI = 1.018-3.433]. For HT, the frequencies of DQB1*0302-DQA1*0501 haplotype [28.8% (21of 73) vs. 14.5% (27 of 186), P = 0.008, OR = 2.378, CI = 1.241-4.558] and DQB1*0302-DQA1*0301 haplotype [60.2% (44 of 73) vs. 38.7% (72 of 186), P = 0.002, OR = 2.402, CI = 1.381-4.180] were significantly higher in patients. On the other hand, weak association was found between HT and DQA1*0301 allele [32.9% (24 of 73) vs. 20.9% (39 of 186), P = 0.044, OR = 1.846, CI = 1.011-3.373]. Findings show that DQB1*0302-DQA1*0501 and DQB1*0302-DQA1*0301 haplotypes may play a role in the pathogenesis of HT in the Lebanese population. For the 49A/G CTLA-4 polymorphism, no significant difference was found between patients and controls.

[Analysis of serum levels of nesfatin-1 in children and adolescents with autoimmune thyroid diseases].

PubMed

Sawicka, Beata; Bossowski, Artur

2013-01-01

Overweight and diseases connected with it are an increasing problem in children and adolescents. Thyroid disease leads to a change of weight - in hyperthyroidism body mass is reduced whereas in hypothyroidism it is increased. It is emphasized that changes in hormones such as peptide levels are in close relationship with the regulation of body mass. Nesfatin-1 is a recently described anorexigenic peptide produced by the brain. Nesfatin-1 also reduces body weight gain, suggesting a role as a new modulator of energy balance. Excess nesfatin in the brain leads to a loss of appetite, less frequent hunger, a `sense of fullness´, and a drop in body fat and weight. A lack of nesfatin-1 in the brain leads to an increase of appetite, more frequent episodes of hunger, an increase of body fat and weight, and the inability to `feel full´. Aim of the study was to evaluate nesfatin-1 levels in young patients with untreated Graves´ disease, subclinical Hashimoto´ thyroiditis, and in healthy children. The study group formed 78 patients of the Outpatient Endocrinology Clinic of Pediatrics, Endocrinology, Diabetology with Cardiology Division. In all the patients, nesfatin level was analyzed by the ELISA´s method. In the group with hyperthyroidism in Graves´ disease lower levels of nesfatin-1 were found compared to the group of healthy children (19.37 vs 32.96 ng/ml; p<0.02); after appropriate treatment in that group the levels of nesfatin-1 were higher compared to the group with hyperthyroidism, but lower compared to the group of healthy children (20.35 vs 32.96 ng/ml; NS). On the other hand, nesfatin-1 levels were lower in children with untreated subclinical hypothyroidism in Hashimoto´s thyroiditis compared to the group of healthy children (17.2 vs32.96 ng/ml; p<0.002). After treatment of L-thyroxine lower levels of nesfatin-1 were found compared to the control group (14.5 vs 32.96 ng/ml; NS). No relationship between nesfatin-1 and thyroid hormones was observed. It might be that disturbances in thyroid hormones in thyroid diseases do not have an essential effect on changes of nesfatin-1 - an appetite-controlling hormone/peptide. Secondly, nesfatin-1 levels were lower in children with untreated autoimmune thyroid diseases, however, the mechanism is also unknown.

Prevalence of thyroid dysfunction in untreated cancer patients: a cross-sectional study.

PubMed

Dişel, Umut; Beşen, Ayberk; Karadeniz, Cemile; Mertsoylu, Hüseyin; Sezer, Ahmet; Köse, Fatih; TanerSümbül, Ahmet; Gürkut, Ozlem; Muallaoğlu, Sadik; Abali, Hüseyin; Ozyilkan, Ozgür

2012-12-01

The relationship between thyroid disease and cancer (and cancer therapies) has been under investigation for years. Factors that increase the risk for thyroid disease include iodine deficiency, autoimmune disorders, old age, and pregnancy. The screening policy for thyroid disease in the healthy population is not precisely defined, and the frequency of thyroid dysfunction in untreated cancer patients has not been investigated in any great detail. This study was designed to compare the prevalence of thyroid dysfunction in 457 untreated cancer patients at the time of initial diagnosis to that of 373 age- and sex-matched subjects who were healthy and cancer-free (control group). Thyroid dysfunction was found in 29.5 % (135/457) of the cancer patients, while only 15.4 % (56/373) of the control group had thyroid dysfunction (p = 0.0001). The most prevalent abnormality was euthyroid sick syndrome (14.0 %, 64/457). Overt and subclinical hyperthyroidism and overt hypothyroidism were observed more frequently in cancer patients than the control group, and these differences were all statistically significant. Thyroid dysfunction was more frequent in patients with poor performance scores and those over the age of 50 years. These data indicate that alterations in thyroid hormone metabolism are twice as common in patients with untreated cancer than in control subjects. Those alterations may lead to delayed diagnosis, suboptimal treatment, and a poorer prognosis. In all, this study suggests that screening with thyroid function tests is strongly recommended in all newly diagnosed cancer patients.

[Lymphoproliferative disease in patients with autoimmune and inflammatory diseases: significance of antigenic stimulation and inflammatory processes].

PubMed

Tvarůzková, Zuzana; Pavlová, Sárka; Doubek, Michael; Mayer, Jirí; Pospísilová, Sárka

2011-01-01

Evidence has been growing that the pathogenesis of lymphoproliferative disease involves immune processes deregulation. It is believed that antigens or immunological elements can trigger transformation of normal lymphocyte polyclonal population into monoclonal neoplastic disorder--lymphoproliferative disease. Extensive studies point to the link between malignant lymphoma development and autoimmune or inflammatory diseases--namely rheumatoid arthritis, Sjörgen's syndrome, coeliac disease, systemic lupus erythematosus or thyroiditis. Increased risk of lymphoproliferative disease development was also proved for some infections. These infections involve both viral (e.g. Epstein-Barr virus, HIV or hepatitis C virus) and bacterial agents (e.g. Helicobacter pylori, Borrelia burgdorferi). Besides various lymphomas, the links to autoimmune/inflammatory diseases have also been described in chronic lymphocytic leukaemia. Regarding clinical medicine, it is necessary to distinguish patients with autoimmune, inflammatory and infectious diseases who are at the increased risk of tumour development. New approaches must be found to lower this risk. Also, the relationship between autoimmune/inflammatory disease therapy and lymphoma development should be clarified. Although lymphomas associated with autoimmune and inflammatory diseases represent only a small proportion of all lymphomas, any new findings regarding these diseases can cast light on lymphoma pathogenesis as a whole.

Severe aplastic anaemia and Grave's disease in a paediatric patient.

PubMed

Kumar, Manjusha; Goldman, Jeffrey

2002-07-01

Severe aplastic anaemia (SAA) is considered to be an autoimmune disorder affecting the haematopoietic cells and most often is idiopathic. An association between SAA and other autoimmune diseases is rare and has been described in adults for eosinophilic fasciitis, thymomas, systemic lupus erythematosus and thyroid disorders. We describe the first paediatric patient with chronic relapsing SAA and Grave's disease. We discuss the difficulty in diagnosis of Grave's disease, the possibility of its manifestation due to withdrawal of immunosuppressants, and issues to consider in the treatment of this disease in the setting of bone marrow failure.

Scurfy mice: A model for autoimmune disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Godfrey, V.L.

1993-01-01

Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work somore » well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.« less

Massive pericardial effusion and rhabdomyolysis secondary to untreated severe hypothyroidism: the first report.

PubMed

Zare-Khormizi, M R; Rahmanian, M; Pourrajab, F; Akbarnia, S

2014-10-01

Hypothyroidism is an endocrine disease with various clinical manifestations. It is a rare cause for rhabdomyolysis and massive pericardial effusion. We describe a case of severe hypothyroidism secondary to autoimmune hashimoto thyroiditis with massive pericardial effusion and rhabdomyolysis. Improvement of mentioned complications after hypothyroidism treatment and rule out of other possible causes are supportive clues that hypothyroidism is the main cause of patient's rare presentation. With the best of our knowledge, it is the first report of rhabdomyolysis and massive pericardial effusion coincidence in a patient of adult population with primary uncontrolled hypothyroidism for years.

Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study.

PubMed

Bares, R; Khalid, N; Daniel, H; Dittmann, H; Reimold, M; Gallwitz, B; Schmotzer, C

2016-07-01

Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.

Patterns of Interferon-Alpha–Induced Thyroid Dysfunction Vary with Ethnicity, Sex, Smoking Status, and Pretreatment Thyrotropin in an International Cohort of Patients Treated for Hepatitis C

PubMed Central

Ghazarian, Sharon R.; Rosen, Antony; Ladenson, Paul W.

2013-01-01

Background Interferon-alpha (IFNα)–induced thyroid dysfunction occurs in up to 20% of patients undergoing therapy for hepatitis C. The diversity of thyroid disease presentations suggests that several different pathological mechanisms are involved, such as autoimmunity and direct toxicity. Elucidating the relationships between risk factors and disease phenotype provides insight into the mechanisms of disease pathophysiology. Methods We studied 869 euthyroid patients from the ACHIEVE 2/3 trial, a randomized international clinical trial comparing pegylated-IFNα2a weekly or albumin-IFNα2b every 2 weeks for up to 24 weeks in patients with hepatitis C, genotype 2 or 3, from 136 centers. The study population was 60% male and 55% white. Serum thyrotropin (TSH) and free thyroxine were measured before therapy, monthly during treatment from week 8, and at 4- and 12-week follow-up visits. Results Overall, 181 (20.8%) participants had at least one abnormal TSH during the study. Low TSH occurred in 71 (8.2%), of whom 30 (3.5%) had a suppressed TSH below 0.1 mU/L. Hypothyroidism occurred in 53 patients (6.1%), with peak TSH above 10 mU/L in 12 patients (1.4%). Fifty-seven patients had a biphasic thyroiditis (6.6%), with extreme values for the nadir and/or peak TSH in all but one. Medical therapy was given to one thyrotoxic patient, four hypothyroid patients, and 26 biphasic thyroiditis patients. Multivariate logistic regression analysis demonstrated that biphasic thyroiditis is associated with being female and higher pretreatment serum TSH, whereas being Asian or a current smoker decreased the risk of thyroiditis. Hypo- and hyperthyroidism are most strongly predicted by the pretreatment TSH. Conclusions Biphasic thyroiditis accounted for the majority (58%) of clinically relevant IFNα-induced thyroid dysfunction. We confirmed our recent findings in a related cohort that female sex is a risk factor for thyroiditis but not hypothyroidism. Further, in this large multiethnic study, the risk of thyroiditis is dramatically increased, specifically for white women. Smoking was found to be protective of thyroiditis. These results support closer monitoring of women and those with a serum TSH at the extremes of the normal range during therapy so that prompt intervention can mitigate the consequences of thyroid dysfunction associated with IFNα treatment. PMID:23517287

Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison's disease.

PubMed

Fichna, Marta; Rogowicz-Frontczak, Anita; Żurawek, Magdalena; Fichna, Piotr; Gryczyńska, Maria; Zozulińska-Ziółkiewicz, Dorota; Ruchała, Marek

2016-07-01

Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1-67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.

Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.

PubMed

Hasham, Alia; Zhang, Weijia; Lotay, Vaneet; Haggerty, Shannon; Stefan, Mihaela; Concepcion, Erlinda; Dieterich, Douglas T; Tomer, Yaron

2013-08-01

Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFNα) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFNα and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFNα treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFNα-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFNα. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFNα. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT. Published by Elsevier Ltd.

GENETIC ANALYSIS OF INTERFERON INDUCED THYROIDITIS (IIT): EVIDENCE FOR A KEY ROLE FOR MHC AND APOPTOSIS RELATED GENES AND PATHWAYS

PubMed Central

Hasham, Alia; Zhang, Weijia; Lotay, Vaneet; Haggerty, Shannon; Stefan, Mihaela; Concepcion, Erlinda; Dieterich, Douglas T.; Tomer, Yaron

2013-01-01

Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFNα) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFNα and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFNα treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFNα-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFNα. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFNα. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT. PMID:23683877

Elevated levels of circulating thyroid hormone do not cause the medical sequelae of hyperthyroidism.

PubMed

Kelly, Tammas; Denmark, Lawrence; Lieberman, Daniel Z

2016-11-03

Clinicians have been reluctant to use high dose thyroid (HDT) to treat affective disorders because high circulating levels of thyroid hormone have traditionally been equated with hyperthyroidism, and understood as the cause of the medical sequelae of hyperthyroidism, such as osteoporosis and cardiac abnormalities. This conclusion is not supported by (HDT) research. A literature review of research related to the morbidity and mortality of HDT treatment was performed. There exists a large body of research involving the use of HDT treatment to prevent the recurrence of differentiated thyroid cancer and to treat affective disorders. A review of this literature finds a lack of support for HDT as a cause of osteoporosis, nor is there support for an increase in morbidity or mortality associated with HDT. This finding contrasts with the well-established morbidity and mortality associated with Graves' disease, thyroiditis, and other endogenous forms of hyperthyroidism. The lack of evidence that exogenous HDT causes osteoporosis, cardiac abnormalities or increases mortality compared with the significant morbidity and mortality of hyperthyroidism requires an alternative cause for the medical sequelae of hyperthyroidism. One possibility is an autoimmune mechanism. High circulating levels of thyroid hormone is not the cause of the sequela of hyperthyroidism. The reluctance to using high dose thyroid is unwarranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathophysiology and laboratory diagnosis of pernicious anemia.

PubMed

Toh, Ban-Hock

2017-02-01

Pernicious anemia is the hematologic manifestation of chronic atrophic gastritis affecting the corpus of the stomach that denudes the gastric mucosa of gastric parietal cells. Asymptomatic autoimmune gastritis, a chronic inflammatory disease of the gastric mucosa, precedes the onset of corpus atrophy by 10-20 years. The gastritis arises from activation of pathologic Th1 CD4 T cells to gastric H/K ATPase that is normally resident on gastric mucosal secretory membranes. The onset of autoimmune gastritis is marked by circulating parietal cell antibody to gastric H/K ATPase. Gastric parietal cells produce two essential biologics: intrinsic factor and HCl acid. Pernicious anemia is a consequence of intrinsic factor loss and neutralizing intrinsic factor antibody that impairs cobalamin absorption. Acid loss leads to iron deficiency anemia that precedes cobalamin-deficient pernicious anemia by 20 years. Laboratory diagnosis rests on parietal cell antibody with or without intrinsic factor antibody, cobalamin-deficient megaloblastic anemia and elevated serum gastrin from loss of acid secretion. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus.

Structural–Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work

PubMed Central

Kleinau, Gunnar; Worth, Catherine L.; Kreuchwig, Annika; Biebermann, Heike; Marcinkowski, Patrick; Scheerer, Patrick; Krause, Gerd

2017-01-01

The thyroid-stimulating hormone receptor (TSHR) is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs). TSHR and its endogenous ligand thyrotropin (TSH) are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy) or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016) concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other class A GPCRs to understand the molecular activation mechanisms of this receptor comprehensively. Finally, limitations of current knowledge and lack of information are discussed highlighting the need for intensified efforts toward TSHR structure elucidation. PMID:28484426

Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity

PubMed Central

Fodor, James; Riley, Blake; Godlewska, Marlena; Góra, Monika; Czarnocka, Barbara; Banga, J Paul; Hoke, David E.; Kass, Itamar; Buckle, Ashley M.

2015-01-01

Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto’s disease—the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The “trans” model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO)-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the “cis” model favours it slightly over the “trans” model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its conformational properties, and its proximity to the membrane, when interpreting epitope-mapping data. PMID:26623656

Modelling of Thyroid Peroxidase Reveals Insights into Its Enzyme Function and Autoantigenicity.

PubMed

Le, Sarah N; Porebski, Benjamin T; McCoey, Julia; Fodor, James; Riley, Blake; Godlewska, Marlena; Góra, Monika; Czarnocka, Barbara; Banga, J Paul; Hoke, David E; Kass, Itamar; Buckle, Ashley M

2015-01-01

Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO has been a major target for structural studies for over 20 years; however, to date, the structure of TPO remains to be determined. We have used a molecular modelling approach to investigate plausible modes of TPO structure and dimer organisation. Sequence features of the C-terminus are consistent with a coiled-coil dimerization motif that most likely anchors the TPO dimer in the apical membrane of thyroid follicular cells. Two contrasting models of TPO were produced, differing in the orientation and exposure of their active sites relative to the membrane. Both models are equally plausible based upon the known enzymatic function of TPO. The "trans" model places IDR-B on the membrane-facing side of the myeloperoxidase (MPO)-like domain, potentially hindering access of autoantibodies, necessitating considerable conformational change, and perhaps even dissociation of the dimer into monomers. IDR-A spans MPO- and CCP-like domains and is relatively fragmented compared to IDR-B, therefore most likely requiring domain rearrangements in order to coalesce into one compact epitope. Less epitope fragmentation and higher solvent accessibility of the "cis" model favours it slightly over the "trans" model. Here, IDR-B clusters towards the surface of the MPO-like domain facing the thyroid follicular lumen preventing steric hindrance of autoantibodies. However, conformational rearrangements may still be necessary to allow full engagement with autoantibodies, with IDR-B on both models being close to the dimer interface. Taken together, the modelling highlights the need to consider the oligomeric state of TPO, its conformational properties, and its proximity to the membrane, when interpreting epitope-mapping data.

Increased Risk of Long-Term Sickness Absence, Lower Rate of Return to Work, and Higher Risk of Unemployment and Disability Pensioning for Thyroid Patients: A Danish Register-Based Cohort Study

PubMed Central

Watt, T.; Pedersen, J.; Bonnema, S. J.; Hegedüs, L.; Rasmussen, A. K.; Feldt-Rasmussen, U.; Bjorner, J. B.

2014-01-01

Context: Little is known about how thyroid diseases affect work ability. Objective: The objective of this study was to evaluate the risk of work disability for patients with thyroid disease compared with the general population. Design, Setting, and Participants: In a longitudinal register study, outpatients (n = 862) with nontoxic goiter, hyperthyroidism, Graves' orbitopathy (GO), autoimmune hypothyroidism, or other thyroid diseases and their matched controls (n = 7043) were observed in the years 1994–2011 in Danish national registers of social benefits, health, and work characteristics. Cox regression analyses estimated adjusted hazard ratios (HRs) for the first year after diagnosis and subsequent years. Main Outcome Measures: Transitions between work, long-term sickness absence, unemployment, and disability pension were measured. Results: Patients differed significantly from the general population with regard to sickness absence, disability pension, return from sickness absence, and unemployment. In the first year after diagnosis, higher risks of sickness absence was seen for GO (HR 6.94) and other hyperthyroid patients (HR 2.08), who also had lower probability of returning from sickness absence (HR 0.62) and higher risk of disability pension (HR 4.15). Patients with autoimmune hypothyroidism showed a lower probability of returning from sickness absence (HR 0.62). In subsequent years, GO patients had significantly higher risk of sickness absence (HR 2.08), lower probability of return from sickness absence (HR 0.51), and unemployment (HR 0.52) and a higher risk of disability pension (HR 4.40). Hyperthyroid patients also had difficulties returning from sickness absence (HR 0.71). Conclusions: Thyroid patients' risk of work disability is most pronounced in the first year after diagnosis and attenuates in subsequent years. GO patients have the highest risk of work disability. PMID:24937367

Is There an Association Between Heparin-Induced Thrombocytopenia (HIT) and Autoimmune Disease?

PubMed

Klinkhammer, Brent; Gruchalla, Michael

2018-03-01

Heparin-induced thrombocytopenia (HIT) is a drug-induced, immunoglobulin G medicated autoimmune disorder associated with several negative clinical outcomes including increased morbidity, mortality, and increased medical costs. Previous studies have shown associations between comorbid autoimmune diseases, but there is little known about associations between HIT and autoimmunity. To provide clinical data to suggest an association between HIT and autoimmunity. Retrospective chart review of 59 cases with a diagnosis of HIT and 251 matched controls without a HIT diagnosis, comparing the prevalence of autoimmunity in each group. A single, large upper Midwest health care system. Patients with a diagnosis of HIT were significantly more likely to have a comorbid autoimmune disease than those without a HIT diagnosis (55.9% vs 10.8%, P < 0.001). In disease-specific analyses, patients with a diagnosis of HIT were significantly more likely to have a diagnosis of antiphospholipid syndrome (15.3% vs 0.0%, P < 0.001), systemic lupus erythematous (8.5% vs 0.4%, P = 0.001), rheumatoid arthritis (5.1% vs 0.0%, P = 0.007), Hashimoto's thyroiditis (13.6% vs 3.6%, P = 0.006), or nonischemic cardiomyopathy (5.1% vs 0.0%, P = 0.007). Patients diagnosed with HIT were significantly older than controls ( P < 0.001). This novel study gives evidence to suggest an association between HIT and autoimmune disease and suggests a need for more research into the relationship between HIT and autoimmunity. These results could alter the anticoagulation management of venous thromboembolism and acute coronary syndrome in patients with a previously identified autoimmune disease. Copyright© Wisconsin Medical Society.

Prevalence of thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes and diabetes type 1.

PubMed

Velkoska Nakova, V; Krstevska, B; Dimitrovski, Ch; Simeonova, S; Hadzi-Lega, M; Serafimoski, V

2010-01-01

The aim of the present study was to determine the prevalence of abnormal thyroid function and antithyroid antibodies during pregnancy in women with diabetes type 1 and gestational diabetes mellitus (GDM). The study group included 83 pregnant women who attended the Outpatient Department of the Endocrinology, Diabetes and Metabolic Disorders Clinic in the period from 05.2009 to 11.2009. The one hundred-g. oral glucose tolerance test (OGTT) was conducted on the pregnant women except for women with diabetes type 1. Thyroid functions were evaluated in all the pregnant women. After routine screening for GDM, thirty of the pregnant women were healthy and GDM was diagnosed in forty of them. The rest, thirteen women, had diabetes type 1. The women who developed GDM showed a mean free thyroxin concentration (fT4) significantly lower than that observed in the healthy pregnant women and women with diabetes type 1. Among the pregnant women with GDM, 10 women or 25% had fT4 concentrations below the lower cut-off with normal thyroid-stimulating hormone concentrations (TSH). A statistically significant difference was found in the prevalence of antithyroid antibodies (anti-TPO) between the (30%) women with diabetes type 1 and (10%) healthy pregnant women (p<0.05). In the women positive for anti-TPO, TSH was significantly higher (p<0.05). The significantly higher prevalence of hypothyroxinemia in GDM pregnancies and anti-TPO titres in pregnancies with diabetes type 1, than in healthy pregnant women warrants routine screening for thyroid abnormalities in these groups of pregnant women.

Frequency of Celiac Disease in Patients with Hypothyroidism

PubMed Central

Mehrdad, Mojtaba; Mansour-Ghanaei, Fariborz; Mohammadi, Fereshteh; Joukar, Farahnaz; Dodangeh, Salimeh; Mansour-Ghanaei, Roya

2012-01-01

Background. Celiac disease (CD) is closely associated with other autoimmune endocrine disorders, particularly autoimmune thyroid disease. The aim of this study was to find the frequency of celiac disease in patients with hypothyroidism in Guilan province, north of Iran. Methods. A total of 454 consecutive patients with hypothyroidism underwent celiac serological tests antiGliadin antibodies (AGA), antitissue transglutaminase antibodies (IgA-tTG) and antiendomysial antibodies (EMA-IgA). Small intestinal biopsy was performed when any of celiac serological tests was positive. Results. Eleven (2.4%) patients were positive for celiac serology, and two patients with documented villous atrophy were diagnosed with classic CD (0.4%; 95%). Two patients with classic CD had Hashimoto's thyroiditis (HT) (0.6%; 95%). Six (54.5%) of 11 were suffering from overt hypothyroidism and 45.5% from subclinical hypothyroidism. Six (54.5%) had HT, and 45.5% had nonautoimmune hypothyroidism. Conclusions. In this study, prevalence of CD was lower than other studies. Most of the patients with CD were suffering from HT, but there was no significant statistical relation between CD and HT. PMID:22545223

CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves’ disease and Hashimoto's thyroiditis)

PubMed Central

Pastuszak-Lewandoska, Dorota; Sewerynek, Ewa; Domańska, Daria; Gładyś, Aleksandra; Skrzypczak, Renata

2012-01-01

Introduction Autoimmune thyroid disease (AITD) is associated with both genetic and environmental factors which lead to the overactivity of immune system. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main genetic factors determining the susceptibility to AITD (Hashimoto's thyroiditis, HT and Graves' disease, GD) development. The aim of the study was to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients. Material and methods Molecular analysis involved AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism method, using three restriction enzymes: Fnu4HI (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G). Results Statistical analysis (χ2 test) confirmed significant differences between the studied groups concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more frequent in AITD group and OR analysis suggested that it might increase the susceptibility to HT. In GD patients, OR analysis revealed statistically significant relationship with the presence of G allele. In controls, CTLA-4 A/A genotype frequency was significantly increased suggesting a protective effect. There were no statistically significant differences regarding frequencies of other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60 A/G) between the studied groups. Conclusions CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients. PMID:22851994

CTLA-4 gene polymorphisms and their influence on predisposition to autoimmune thyroid diseases (Graves' disease and Hashimoto's thyroiditis).

PubMed

Pastuszak-Lewandoska, Dorota; Sewerynek, Ewa; Domańska, Daria; Gładyś, Aleksandra; Skrzypczak, Renata; Brzeziańska, Ewa

2012-07-04

Autoimmune thyroid disease (AITD) is associated with both genetic and environmental factors which lead to the overactivity of immune system. Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) gene polymorphisms belong to the main genetic factors determining the susceptibility to AITD (Hashimoto's thyroiditis, HT and Graves' disease, GD) development. The aim of the study was to evaluate the relationship between CTLA-4 polymorphisms (A49G, 1822 C/T and CT60 A/G) and HT and/or GD in Polish patients. Molecular analysis involved AITD group, consisting of HT (n=28) and GD (n=14) patients, and a control group of healthy persons (n=20). Genomic DNA was isolated from peripheral blood and CTLA-4 polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism method, using three restriction enzymes: Fnu4HI (A49G), BsmAI (1822 C/T) and BsaAI (CT60 A/G). Statistical analysis (χ(2) test) confirmed significant differences between the studied groups concerning CTLA-4 A49G genotypes. CTLA-4 A/G genotype was significantly more frequent in AITD group and OR analysis suggested that it might increase the susceptibility to HT. In GD patients, OR analysis revealed statistically significant relationship with the presence of G allele. In controls, CTLA-4 A/A genotype frequency was significantly increased suggesting a protective effect. There were no statistically significant differences regarding frequencies of other genotypes and polymorphic alleles of the CTLA-4 gene (1822 C/T and CT60 A/G) between the studied groups. CTLA-4 A49G polymorphism seems to be an important genetic determinant of the risk of HT and GD in Polish patients.

The Impact of Subclinical Hypothyroidism or Thyroid Autoimmunity on Coronary Vasospasm in Patients without Associated Cardiovascular Risk Factors

PubMed Central

Lee, Sea-Won; Kim, Hyun-Su; Heo, Jung-Ho; Cha, Tae-Joon

2015-01-01

Background and Objectives Subclinical hypothyroidism is associated with endothelial dysfunction and impaired coronary flow reserve. However, the effect of subclinical hypothyroidism or thyroid autoimmunity on variant angina has yet to be determined. Subjects and Methods Among 385 consecutive patients without associated cardiovascular risk factors who underwent coronary angiography with the ergonovine provocation test (EPT), 165 had a positive EPT {EPT(+)} and 220 had a negative EPT {EPT(-)}. The relationship between coronary artery spasm and the presence of subclinical thyroid dysfunction as well as serum thyroid peroxidase autoantibody (TPO Ab) was evaluated. Results The proportion of patients with subclinical hypothyroidism among those who were EPT(+) was significantly higher than that in those who were EPT(-) (18% vs. 11%, p=0.001). However, there was no significant difference in the proportion of patients with subclinical hyperthyroidism between the groups. Moreover, EPT(+) patients showed significantly more positive TPO Ab (33% vs. 14%, p<0.001) than those with EPT(-). There was a positive correlation between EPT(+) and TPO positivity (r=0.226, p<0.001), subclinical hypothyroidism (r=0.112, p=0.033), and body mass index (r=0.123, p=0.018). Binary logistic regression analysis revealed that the significant predictors of EPT(+) were body mass index {adjusted odds ratio (OR)=1.042, 95% confidence interval (CI)=1.005-1.080}, presence of subclinical hypothyroidism (OR=3.047, 95% CI=1.083-8.572), TPO Ab titer (OR=1.028, 95% CI=1.015-1.041), and the presence of TPO Ab (OR=4.904, 95% CI=1.544-15.567). Conclusion Subclinical hypothyroidism and the presence of TPO Ab are significantly associated with coronary vasospasm in patients without cardiovascular risk factors. PMID:25810734

Endocrine manifestations of Down syndrome.

PubMed

Whooten, Rachel; Schmitt, Jessica; Schwartz, Alison

2018-02-01

To summarize the recent developments in endocrine disorders associated with Down syndrome. Current research regarding bone health and Down syndrome continues to show an increased prevalence of low bone mass and highlights the importance of considering short stature when interpreting dual energy x-ray absorptiometry. The underlying cause of low bone density is an area of active research and will shape treatment and preventive measures. Risk of thyroid disease is present throughout the life course in individuals with Down syndrome. New approaches and understanding of the pathophysiology and management of subclinical hypothyroidism continue to be explored. Individuals with Down syndrome are also at risk for other autoimmune conditions, with recent research revealing the role of the increased expression of the Autoimmune Regulatory gene on 21st chromosome. Lastly, Down-syndrome-specific growth charts were recently published and provide a better assessment of growth. Recent research confirms and expands on the previously known endocrinopathies in Down syndrome and provides more insight into potential underlying mechanisms.

Distal renal tubular acidosis in two children with acquired hypothyroidism.

PubMed

Guerra-Hernández, Norma E; Ordaz-López, Karen V; Vargas-Poussou, Rosa; Escobar-Pérez, Laura; García-Nieto, Víctor M

2018-04-28

Two cases of children diagnosed with renal tubular acidosis (RTA) associated with autoimmune hypothyroidism are presented. Case 1 developed an intestinal ileus at the age of five in the context of a respiratory problem. The tests performed confirmed metabolic acidosis, hyperchloraemia, hypokalaemia and nephrocalcinosis. Case 2 was diagnosed with hypothyroidism at the age of 11, and with RTA two years later. In both patients, the diagnosis of RTA was verified when decreased maximum urinary pCO 2 was found. In case 2, a proximal bicarbonate leak (type 3 RTA) was also confirmed. This was the first case to be published on the topic. The causes of RTA in patients with hypothyroidism are reviewed. The deleterious effect on the kidneys may be due to the absence of thyroid hormone and/or autoantibodies in the cases of autoimmune hypothyroidism. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population.

PubMed

Koc, Arzuhan; Batar, Bahadir; Celik, Ozlem; Onaran, Ilhan; Tasan, Ertugrul; Sultuybek, Gonul Kanigur

2014-07-01

Hashimoto thyroiditis (HT) is a chronic inflammatory autoimmune disease of thyroid gland affected by interaction of multiple genes and various cytokines. Variants in the genes coding for the NFKB and IKB proteins can be potentially involved in the development of the inflammatory diseases. NFKB, a key transcription factor of the regulation of immune responses, is interesting candidate for association studies about autoimmune disorder. The aim of the present study was to investigate the relationship between NFKB1 and NFKBIA (NFKB1 inhibitor gene) polymorphisms, and the risk of HT in a Turkish Population in the context of IL-6 serum levels which may contribute to susceptibility to the disease. We analyzed the distribution of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms using PCR-RFLP method and IL-6 serum levels using ELISA method in 120 HT patients and 190 healthy controls in Turkish population. Although, there was no statistical significant difference in distribution of the genotypes and alleles of NFKB1-94ins/del ATTG or NFKBIA 3'UTR A→G polymorphisms in patients and control subjects as single, ins/ins/GG combined genotype had protective effect on the disease when compared to ins/ins/AG combined genotype as combined genotypes of both polymorphisms. In addition to this finding, IL-6 serum levels in HT patients with del/del genotype were significantly higher than in patients with del/ins genotype (p<0.001). According to the combined genotype analysis of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms, IL-6 levels were also higher in patients with del/del genotype when at least one G allele existing (p=0.007). Therefore, our findings suggest that the functional promoter NFKB1-94ins/del ATTG polymorphism was significantly associated with population HT disease through acting by directly modulating IL-6 serum levels. Copyright © 2014 Elsevier GmbH. All rights reserved.

[Classification and etiology of hyperthyroidism].

PubMed

Łacka, Katarzyna; Fraczek, Magdalena Maria

2014-03-01

The prevalence of hyperthyroidism in women is between 0.5-2% and it is 10 times less common in men. The most common causes are Graves' disease, toxic multinodular goiter, and autonomously functioning thyroid adenoma. Rare causes of hyperthyroidisms are as follow: pituitary adenoma, autoimmune thyroiditis (Hashitoxicosis), levothyroxine overdose, inadequate iodine supplementation (including amiodaron induced hyperthyroidism, iodine-based contrast media), hCG excess (pregnancy, gestational trophoblastic disease, germ-cell tumors), drug induced hyperthyroidism, differentiated thyroid carcinomas and/or their metastases, struma ovarii, and familial nonautoimmune hyperthyroidism. This article focuses on the current data of etiopathogenesis of hyperthyroidisms. Genetic factors (like HLA-DR3,CD40, CTLA-4, PTPN22, FOXP3 CD25) and thyroid specific genes (thyroglobulin, TSHR, G(s)alpha) and environmental and endogenous factors (such as age, iodine, selenium, emotional stress, smoking, gender, pregnancy, sex hormones, fetal microchimerism, fetal growth, bacterial infections, viral infections, allergies, drugs (alemtuzumab, interferon alpha, iplimumab/tremelimumab, tyrosine kinase inhibitors, denileukindiftitox, thalidomide/lenalidomide, exposition to fallout and radiotherapy) have been described.

Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakaguchi, N.; Sakaguchi, S.; Miyai, K.

1992-11-01

Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and themore » peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.« less

Does One Size Fit Everyone? Replacement Dose of Levothyroxine in Long-standing Primary Hypothyroidism in Adults

PubMed Central

Singh, Rekha

2017-01-01

Objectives: The recommended starting dose of levothyroxine (LT4) in primary hypothyroidism is 1.6 μg/kg body weight and is based on presumption of minimal residual thyroid function in autoimmune hypothyroidism. This study aimed at finding the range and determining factors for LT4 dose in long-standing hypothyroidism. Methods: A cross-sectional study of individuals with primary autoimmune hypothyroidism on LT4 replacement was done between March 2015 and January 2016. Individuals enrolled were euthyroid based on recent serum thyroid-stimulating hormone. The inclusion criteria included LT4 intake in the morning empty stomach, maintenance of at least 1-h food gap, not on medications known to hamper LT4 absorption within 4 h of dosing, diagnosis of hypothyroidism at least for 1 year, and on a minimum 25 μg LT4. P < 0.05 was considered statistically significant. Results: A total of 346 individuals (290 women and 56 men; 214 premenopausal and 76 postmenopausal women) were enrolled. The mean duration of hypothyroidism and age were 5.7 years and 42.1 years, respectively. The range and mean of absolute LT4 daily dose (ADD), LT4 dose based on body weight (D/W), and LT4 dose based on ideal body weight (D/IBW) were 25–200 μg daily and 77.1 μg, 0.3–2.82 μg/kg and 1.21 μg/kg, and 0.42–3.5 μg/kg and 1.58 μg/kg, respectively. Duration of hypothyroidism was significant predictors of ADD, D/W, and D/IBW. Gender-based difference in ADD and D/IBW was explained by gender difference in anthropometry. Conclusion: Long-standing primary autoimmune hypothyroidism has variable dose requirement of LT4 for achieving euthyroidism and may be dependent on the degree of residual functional thyroid. Duration of hypothyroidism was significant positive predictor for either ADD, D/W, or D/IBW. PMID:28553595

Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial.

PubMed

Dörr, Helmuth G; Bettendorf, Markus; Binder, Gerhard; Karges, Beate; Kneppo, Carolin; Schmidt, Heinrich; Voss, Egbert; Wabitsch, Martin; Dötsch, Jörg

2015-01-01

Levothyroxine (L-T4) treatment of euthyroid children with Hashimoto thyroiditis (HT) is a controversial issue. We conducted a prospective, randomized, controlled clinical trial. Out of 79 identified euthyroid patients, 59 started the study; 25 patients (21 female, 4 male; age: 11.8 ± 2.3 years) received L-T4 at a mean dose of 1.6 µg/kg (SD, 0.8) daily, and 34 (27 female, 7 male; age: 12.6 ± 1.2 years) were not treated. Patients developing subclinical hypothyroidism during follow-up (n = 13) were treated with L-T4 and removed from the observation group. As the main outcome measures, thyroid gland volume (determined by ultrasound) as well as serum levels of TSH, free T4, and antibodies against thyroid peroxidase and thyroglobulin were assessed every 6 months for 36 months. At the start, the mean thyroid volume (standard deviation score, SDS) was 2.5 in the treatment group and 1.6 in the observation group. There was a constant decline in mean thyroid volume (SDS) from 2.13 (month 12) to 1.12 (month 30) in the treated group, with a delta thyroid volume of -1.01 SDS. In the observation group, the mean delta thyroid volume increased to +0.27 SDS. The change of the delta thyroid volume was statistically significantly different between both groups during the 12- and 30-month time points (p < 0.05). L-T4 had no effect on thyroid function and serum thyroid antibodies. L-T4 treatment can decrease the thyroid volume in euthyroid children with HT, but the effect is limited to a definite time period. © 2015 S. Karger AG, Basel.

Systemic lupus erythematosus and thyroid disease - Experience in a single medical center in Taiwan.

PubMed

Liu, Yu-Chuan; Lin, Wen-Ya; Tsai, Ming-Chin; Fu, Lin-Shien

2017-06-28

To investigate the association of systemic lupus erythematosus (SLE) with thyroid diseases in a medical center in central Taiwan. This is a retrospective cohort of 2796 SLE patients in a tertiary referral medical center from 2000 to 2013. We screened SLE by catastrophic illness registration from national insurance bureau; and thyroid diseases by ICD 9 codes, then confirmed by thyroid function test, auto-antibody, medical and/or surgical intervention. We compared the rate of hyperthyroidism, hypothyroidism and autoimmune thyroid disease (AITD) in SLE patients and the 11,184 match controls. We calculated the rate of these thyroid diseases and positive antibodies to thyroglobulin (ATGAb), thyroid peroxidase (TPOAb) in SLE patients grouped by the presence of overlap syndrome and anti-dsDNA antibody. We also compared the association of thyroid diseases to severe SLE conditions, including renal, central nervous system (CNS) involvement, and thrombocytopenia. Compared to the matched controls, the cumulative incidence of thyroid disease, including hyperthyroidism, hypothyroidism and AITD, were all higher in SLE patients (p < 0.0001). The average age of SLE patients with thyroid diseases patients were older than those without thyroid diseases (p = 0.002). Those had euthyroid AITD were younger than other patients with thyroid diseases (p = 0.02). Up to 30.3% SLE patients had overlap syndrome and had higher relative risk of thyroid diseases than those without overlap syndrome, in terms of hypothyroidism and AITD, but not hyperthyroidism. SLE patients with thyroid diseases also carry higher risk for severe complications such as renal involvement (p = 0.024) central nervous system involvement (p < 0.0001). SLE patients had significantly higher rate of hyperthyroidism, hypothyroidism, and AITD than the matched control. Among lupus patients, the risks of thyroid diseases are even higher in the presence of overlap syndrome. SLE patients with thyroid diseases had higher risk of renal and CNS involvement. Copyright © 2017. Published by Elsevier B.V.

[Progression of right internal carotid artery stenosis in ischemic stroke patient with autoimmune polyglandular syndrome: A case report].

PubMed

Kanazawa, Yuka; Matsuo, Ryu; Fukushima, Yoshihisa; Fukuda, Kenji; Kamouchi, Masahiro; Kitazono, Takanari

2013-01-01

A 40-year-old man who presented with left hemiparesis was admitted to our hospital. He had tachycardia and a fever. He had a 25-year history of insulin therapy for diabetes mellitus. Brain magnetic resonance (MR) images showed fresh infarction in the right hemisphere, and carotid ultrasonography showed stenosis of the right internal carotid artery (ICA). We determined that atherothrombotic brain infarction had likely occurred. After admission, the right ICA became narrow and finally occluded. Computed tomography revealed the presence of a thrombus in the right ICA, and gadolinium-enhanced MRA showed vasculitis of the ICA. In laboratory tests, his thyroid hormones were elevated. He was diagnosed with hyperthyroidism. After treatment, the tachycardia and high fever were improved. Because of a positive anti-glutamic acid decarboxylase antibody test result, he was diagnosed with insulin-dependent diabetes mellitus. We found that he had anti-phospholipid antibody syndrome because he was positive for anti-beta-glycoprotein I antibody. These findings suggested that his condition was autoimmune polyglandular syndrome type 3. He received prednisolone and warfarin. After 3 months, his neurological findings were improved; however, occlusion of the ICA remained. Autoimmunity was considered to be the cause of ICA occlusion. Ischemic stroke with autoimmune polyglandular syndrome is very rare and is associated with progressive carotid lesions in juvenile patients. It is necessary to diagnose and treat this condition as soon as possible.

RAGE polymorphisms and oxidative stress levels in Hashimoto's thyroiditis.

PubMed

Giannakou, Maria; Saltiki, Katerina; Mantzou, Emily; Loukari, Eleni; Philippou, Georgios; Terzidis, Konstantinos; Lili, Kiriaki; Stavrianos, Charalampos; Kyprianou, Miltiades; Alevizaki, Maria

2017-05-01

Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels. A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA. Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 μmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism. Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.

PubMed

Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop; Hegedüs, Laszlo; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

2015-07-01

We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.

Manifestation of Central Diabetes Insipidus in a Patient with Thyroid Storm.

PubMed

Nakamichi, Akiko; Ocho, Kazuki; Oka, Kosuke; Yasuda, Miho; Hasegawa, Kou; Iwamuro, Masaya; Obika, Mikako; Rai, Kammei; Otsuka, Fumio

2018-02-28

We herein report a case of central diabetes insipidus complicated with thyroid storm. A middle-aged woman who was receiving treatment for Graves' disease suddenly complained of polydipsia, polyuria and general fatigue. Laboratory tests showed hyperthyroidism, hypernatremia, hypoosmolar urine and a decreased plasma vasopressin level. The occurrence of central diabetes insipidus with hyperthyroidism was revealed on the basis of pituitary magnetic resonance imaging, a water deprivation test and a desmopressin test. The clinical co-existence of diabetes insipidus and hyperthyroidism is very rare; however, the complication should be considered when hypernatremia and/or dehydration progress in patients with Graves's disease as a common autoimmune-related etiology.

Coherent Somatic Mutation in Autoimmune Disease

PubMed Central

Ross, Kenneth Andrew

2014-01-01

Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

GM-CSF: An Immune Modulatory Cytokine that can Suppress Autoimmunity

PubMed Central

Bhattacharya, Palash; Thiruppathi, Muthusamy; Elshabrawy, Hatem A.; Alharshawi, Khaled; Kumar, Prabhakaran; Prabhakar, Bellur S.

2015-01-01

GM-CSF was originally identified as a colony stimulating factor (CSF) because of its ability to induce granulocyte and macrophage populations from precursor cells. Multiple studies have demonstrated that GM-CSF is also an immune-modulatory cytokine, capable of affecting not only the phenotype of myeloid lineage cells, but also T-cell activation through various myeloid intermediaries. This property has been implicated in the sustenance of several autoimmune diseases like arthritis and multiple sclerosis. In contrast, several studies using animal models have shown that GM-CSF is also capable of suppressing many autoimmune diseases like Crohn's disease, Type-1 diabetes, Myasthenia gravis and experimental autoimmune thyroiditis. Knockout mouse studies have suggested that the role of GM-CSF in maintaining granulocyte and macrophage populations in the physiological steady state is largely redundant. Instead, its immune-modulatory role plays a significant role in the development or resolution of autoimmune diseases. This is mediated either through the differentiation of precursor cells into specialized non-steady state granulocytes, macrophages and dendritic cells, or through the modulation of the phenotype of mature myeloid cells. Thus, outside of myelopoiesis, GM-CSF has a profound role in regulating the immune response and maintaining immunological tolerance. PMID:26113402

Linkage analysis of candidate genes in autoimmune thyroid disease. II. Selected gender-related genes and the X-chromosome. International Consortium for the Genetics of Autoimmune Thyroid Disease.

PubMed

Barbesino, G; Tomer, Y; Concepcion, E S; Davies, T F; Greenberg, D A

1998-09-01

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are autoimmune thyroid diseases (AITD) in which multiple genetic factors are suspected to play an important role. Until now, only a few minor risk factors for these diseases have been identified. Susceptibility seems to be stronger in women, pointing toward a possible role for genes related to sex steroid action or mechanisms related to genes on the X-chromosome. We have studied a total of 45 multiplex families, each containing at least 2 members affected with either GD (55 patients) or HT (72 patients), and used linkage analysis to target as candidate susceptibility loci genes involved in estrogen activity, such as the estrogen receptor alpha and beta and the aromatase genes. We then screened the entire X-chromosome using a set of polymorphic microsatellite markers spanning the whole chromosome. We found a region of the X-chromosome (Xq21.33-22) giving positive logarithm of odds (LOD) scores and then reanalyzed this area with dense markers in a multipoint analysis. Our results excluded linkage to the estrogen receptor alpha and aromatase genes when either the patients with GD only, those with HT only, or those with any AITD were considered as affected. Linkage to the estrogen receptor beta could not be totally ruled out, partly due to incomplete mapping information for the gene itself at this time. The X-chromosome data revealed consistently positive LOD scores (maximum of 1.88 for marker DXS8020 and GD patients) when either definition of affectedness was considered. Analysis of the family data using a multipoint analysis with eight closely linked markers generated LOD scores suggestive of linkage to GD in a chromosomal area (Xq21.33-22) extending for about 6 cM and encompassing four markers. The maximum LOD score (2.5) occurred at DXS8020. In conclusion, we ruled out a major role for estrogen receptor alpha and the aromatase genes in the genetic predisposition to AITD. Estrogen receptor beta remains a candidate locus. We found a locus on Xq21.33-22 linked to GD that may help to explain the female predisposition to GD. Confirmation of these data in HT may require study of an extended number of families because of possible heterogeneity.

Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid Elasticity in Pediatric Patients With Hashimoto Thyroiditis.

PubMed

Yucel, Serap; Ceyhan Bilgici, Meltem; Kara, Cengiz; Can Yilmaz, Gulay; Aydin, H Murat; Elmali, Muzaffer; Tomak, Leman; Saglam, Dilek

2018-05-01

To evaluate the parenchymal elasticity of the thyroid gland with acoustic radiation force impulse imaging in pediatric patients with Hashimoto thyroiditis and to compare it with healthy volunteers. Twenty-six patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17 years were included. The shear wave velocity (SWV) values of both thyroid lobes in both groups were evaluated. The age and sex characteristics of the controls and patients with Hashimoto thyroiditis were similar. The SWV of the thyroid gland in patients with Hashimoto thyroiditis (mean ± SD, 1.67 ± 0.63 m/s) was significantly higher than that in the control group (1.30 ± 0.13 m/s; P < .001). There was no significant difference between the thyroid lobes in both groups. A receiver operating characteristic curve analyses showed an optimal cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 % positive predictive value, and a 75.0% negative predictive value (area under the curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a positive correlation between the SWV values versus anti-thyroperoxidase (Pearson r = 0.46; P = .038). There were no correlations between age, body mass index, thyroid function test results, and anti-thyroglobulin values and versus SWV values. Also, no significant differences were seen between the groups for gland size, gland vascularity, and l-thyroxine treatment. Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis. © 2017 by the American Institute of Ultrasound in Medicine.