Destruction Of Thyroid Cells Research Articles

Alterations in CD4+ T Cell Cytokines Profile in Female Patients with Hashimoto's Thyroiditis Following Vitamin D Supplementation: A Double-blind, Randomized Clinical Trial.

Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors. Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol (1, 25(OH)2D3) at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR. Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFβ) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation. The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT.

The Investigation of Kisspeptin, Spexin and Galanin in Euthyroid Women with Hashimoto’s Thyroiditis

ABSTRACT Objective The hallmarks of Hashimoto’s thyroiditis (HT) include the destruction of thyroid cells by leading to insulin resistance (IR), hypothyroidism, and metabolic abnormalities. Kisspeptin, spexin, and galanin control appetite and body weight (BW) to regulate metabolisms. Here, we sought to determine if galanin, kisspeptin, and spexin are linked to the pathophysiology of HT in euthyroid female individuals. Methods Forty-five women with HT and 45 healthy control women of the same age participated in the current study. The enzyme-linked immunosorbent assay (ELISA) method was used to measure the serum levels of galanin, spexin, and kisspeptin. Results In comparison to the controls, HT patients had significantly higher levels of kisspeptin (p < 0.01), galanin (p < 0.01), anti-thyroid peroxidase (anti-TPO) (p < 0.001), anti-thyroglobulin (anti-Tg) (p < 0.001), and body mass index (BMI) (p < 0.05). The two groups were comparable in terms of spexin, free triiodothyronine-3 (fT3), fT4, thyroid-stimulating hormone (TSH) levels, and homeostatic model assessment for insulin resistance (HOMA-IR). Galanin and kisspeptin were seen to have a positive correlation (p < 0.01; r = 0.786). Conclusions Euthyroid women with HT were found to have higher levels of kisspeptin and galanin. These results imply that kisspeptin and galanin may be linked to the pathogenesis of hypothyroidism, and as a result, we believe that these markers may be beneficial in the early detection and treatment of HT patients.

Impact of single nucleotide polymorphisms of immune checkpoint CTLA-4 (SNP rs231775 and rs5742909) in susceptibility to Hashimoto's thyroiditis patients

Background: Hashimoto thyroiditis is an autoimmune disorder causing thyroid cell destruction. This research aimed to evaluate CTLA-4 expression levels in patients with Hashimoto's thyroiditis, biochemical parameters. As well as understand the risk and protective effects of two CTLA-4 SNPs polymorphisms (rs231775 and rs5742909) in Iraqi patients. Methods: A case control study was conducted on 50 HT patients (5 men and 45 females) were assembled from Baghdad teaching hospital, Baghdad, Iraq. The relative Gene expression method was used to measure the gene expression of CTLA-4 using qRT-PCR. The single nucleotide polymorphisms of (318C/T (rs231775) and +49A/G (rs5742909) were sequenced for data analysis. Results: There was significant increase of serum CTLA-4 levels, similarity fold change of CTLA-4 was significant upregulated in HT patients compared to controls. The allele and genotypes frequencies according to HWB equilibrium showed significant differences in HT patients 318C/T (rs231775) AA genotypes, while no significant differences in the AG, GG genotypes, respectively compared to controls (p&lt;0.05), There were also no significant differences in the CTLA-4 SNP +49A/G (rs5742909), (CC, CT, TT) genotype, respectively. (p&gt;0.05). Both studied SNPs recoded higher upregulation of soluble and fold change of the immune check point (CTLA-4), respectively. Conclusion: The study reveals that CTLA-4 gene SNPs rs231775 and rs5742909 significantly influence soluble and the expression of CTLA-4 levels in HT patients, potentially causing Hashimoto disease and HT incidence and development.

An observational study to determine relationship of serum hydrogen sulphide level in hypothyroid patients in a medical college in Kolkata

Hypothyroidism is an endocrinopathy eventuate due to destruction of thyroid cells incapacitating synthesis of thyroid hormones. HS which is a gas signaling molecule that might protect synthesis and secretion of thyroid hormone by upregulating the expression levels of thyroid hormone synthesis-related proteins and promotingting Thyroid peroxidase (TPO) activity through S-sulphydration of sirtuin-1 (SIRT-1). Depending on this fact we measured the HS level in a group of hypothyroid patient. The plasma H S level in case in our study was 33.95 ± 4.14 micromol/l with the range from 27.82 to 43.94 micromol/l. This was significantly (P&amp;#60; 0.001) lower than age/sex matched healthy controls which was 64.67±4.25 micromol/l, with a range from 49.81 to 80.02 micromol/l. this study also elucidated that plasma HS levels were significantly correlated with level of diagnostic parameters of hypothyroidism.

A novel hybrid model to predict concomitant diseases for Hashimoto’s thyroiditis

Hashimoto’s thyroiditis is an autoimmune disorder characterized by the destruction of thyroid cells through immune-mediated mechanisms involving cells and antibodies. The condition can trigger disturbances in metabolism, leading to the development of other autoimmune diseases, known as concomitant diseases. Multiple concomitant diseases may coexist in a single individual, making it challenging to diagnose and manage them effectively. This study aims to propose a novel hybrid algorithm that classifies concomitant diseases associated with Hashimoto’s thyroiditis based on sequences. The approach involves building distinct prediction models for each class and using the output of one model as input for the subsequent one, resulting in a dynamic decision-making process. Genes associated with concomitant diseases were collected alongside those related to Hashimoto’s thyroiditis, and their sequences were obtained from the NCBI site in fasta format. The hybrid algorithm was evaluated against common machine learning algorithms and their various combinations. The experimental results demonstrate that the proposed hybrid model outperforms existing classification methods in terms of performance metrics. The significance of this study lies in its two distinctive aspects. Firstly, it presents a new benchmarking dataset that has not been previously developed in this field, using diverse methods. Secondly, it proposes a more effective and efficient solution that accounts for the dynamic nature of the dataset. The hybrid approach holds promise in investigating the genetic heterogeneity of complex diseases such as Hashimoto’s thyroiditis and identifying new autoimmune disease genes. Additionally, the results of this study may aid in the development of genetic screening tools and laboratory experiments targeting Hashimoto’s thyroiditis genetic risk factors. New software, models, and techniques for computing, including systems biology, machine learning, and artificial intelligence, are used in our study.

Pathogenesis Markers of Hashimoto's Disease-A Mini Review.

Hashimoto's thyroiditis (HT) is the most common autoimmune disease involving the thyroid gland. HT often clinically manifest as hypothyroidism due to the destruction of thyroid cells mediated by humoral and cellular immunity. The pathogenesis of HT is a complex process in which environmental factors, hereditary inclination, trace elements immune factors, cytokines, and DNA and miRNA all play an important role. Herein, we summarize the precision factors involved in the pathogenesis of HT and offer an update over the past 5 years to provide a theoretical basis for further investigation of the relevant targets for HT treatment.

GRANULYSIN PEPTIDE AND GENE POLYMORPHISM IN THE PATHOGENESIS OF HASHIMOTO THYROIDITIS.

Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Dijetarni faktori i tiroidna disfunkcija

Besides iodine deficiency, autoimmune Hashimoto thyroiditis is the leading cause of hypothyroidism globally, characterized by the increased titer of thyroid autoantibodies and destruction of thyroid cells. Graves' disease is the most common etiology of hyperthyroidism worldwide. Patients with thyroid dysfunction often require dietary modifications. Popular interventions include supplementation with certain vitamins and minerals, as well as trace elements such as iodine and selenium. The intake of food containing goitrogens should be limited. Goitrogens are substances of plant origin that interfere with the production of thyroid hormones, increasing the risk for goiter and hypothyroidism. The primary dietary sources of goitrogens are cruciferous vegetables, soy products, starchy plants, and some fruits. Beyond essential nutrients, there has been an increasing interest in using specific nutraceuticals, including myoinositol, Lcarnitine, melatonin, and resveratrol, as potential preventive and therapeutic agents in thyroid diseases. Even though current evidence promotes some beneficial outcomes of these nutraceuticals, further investigations are needed to clarify dose-dependent effects, duration of supplementation, combination in different clinical settings, and the exact mechanism of their action in thyroid disorders.

The Association of Subclinical Insulin Resistance with Thyroid Autoimmunity in Euthyroid Individuals

SUMMARYHashimoto thyroiditis is characterized by anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies that gradually lead to thyroid cell destruction. As hypothyroidism has been associated with insulin resistance (IR), we aimed to investigate whether IR is associated with thyroid antibody presence and whether the degree of IR correlates with their concentration in euthyroid individuals. A total of 164 non-diabetic, euthyroid individuals, average age 34 years, were included in the study, divided into two groups according to Hashimoto thyroiditis and underwent 5-hour oral glucose tolerance test. The degree of IR was evaluated by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). The Hashimoto thyroiditis group had higher HOMA-IR (p=0.003) and lower glucose levels (p=0.04). HOMA-IR correlated positively with anti-TPO (p<0.001). Linear logistic regression revealed that anti-TPO concentration increased by 18.13 (p=0.001) with each HOMA-IR unit. IR might trigger thyroid antibody production and Hashimoto thyroiditis development, which needs to be evaluated in further larger scale follow up studies.

Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.

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

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.

English

Abstract Hashimoto's thyroiditis is part of the spectrum of autoimmune thyroid diseases characterized by the destruction of thyroid cells by antibody mediated immune processes. Although there are some studies about the association of macroprolactinaemia and interleukin-21 (IL-21) levels with other autoimmune diseases, few studies have been found about Hashimoto's thyroiditis in the literature. In this study, we aimed to see if there is any association between IL-21 and macroprolactin levels with anti-thyroid antibodies. The study included 70 patients with Hashimoto's thyroiditis as the study group and 48 healthy volunteers as the control group. Interleukin-21, prolactin, free thyroxin, thyroid-stimulaing hormone (TSH), antibodies against thyroglobulin (TG) and anti-thyroid peroxidase (anti-TPO) were determined in all participants. The presence of macroprolactinaemia was manifested by polyethylene glycol precipitation method. There was no significant difference between the study and control groups for fT3, fT4, prolactin and macroprolactin levels. We could not find any relationship between prolactin and macroprolactin levels with anti-TPO and anti-TG levels. Although IL-21 levels of the control group were significantly higher than the study group, there was also no correlation between IL-21 and anti-TPO and anti-TG levels. Our results showed that neither macroprolactin nor prolactin levels has any relationship with anti-thyroid antibodies. Contrary to other studies, IL-21 levels of the control group were higher than the study group. We think that new onset studies should be done with larger groups to better understand if there are any relationships of IL-21 and macroprolactin levels with Hashimoto's thyroiditis.

Risk factors and pathogenesis of Hashimoto’s thyroiditis

The aim of this review is to summarize the current knowledge on Hashimoto's thyroiditis and its pathogenesis and to introduce the readers to the basic concept of autoimmune thyroid disease. Hashimoto's thyroiditis and Graves' disease are different expressions of a basically similar autoimmune process, and the clinical appearance reflects the spectrum of the immune response in a particular patient. During this response, cytotoxic autoantibodies, stimulatory autoantibodies, blocking autoantibodies, or cell-mediated autoimmunity may be observed. Persons with classic Hashimoto's thyroiditis have serum antibodies reacting with thyroglobulin and thyroid peroxidase. These antibodies (particularly antibodies against thyroid peroxidase) are complement-fixing immunoglobulins and may be cytotoxic. In addition, many patients have cell-mediated immunity directed against thyroid antigens. Cell mediated-immunity is also a feature of experimental thyroiditis induced in animals by injection of thyroid antigen with adjuvants. Hashimoto's thyroiditis is predominantly the clinical expression of cell-mediated immunity leading to destruction of thyroid cells, which in its severest form causes thyroid failure. The significance of genetic component and nongenetic risk factors (pregnancy, drugs, age, sex, infection, and irradiation) in the development of Hashimoto's thyroiditis is also reviewed. Epidemiologic studies have demonstrated that the genetic component is important in the pathogenesis of Hashimoto's thyroiditis, although the pattern of inheritance is non-Mendelian and is likely to be influenced by subtle variations in the functions of multiple genes. Nongenetic risk factors (environmental factors) are also etiologically important, because the concordance rate in monozygotic twins is below 1.

Autoimmune thyroid diseases: genetic susceptibility of thyroid-specific genes and thyroid autoantigens contributions

Autoimmune thyroid diseases are common polygenic multifactorial disorders with the environment contributing importantly to the emergence of the disease phenotype. Some of the disease manifestations, such as severe thyroid-associated ophthalmopathy, pretibial myxedema and thyroid antigen/antibody immune complex nephritis are unusual to rare. The spectrum of autoimmune thyroid diseases includes: Graves' disease (GD), Hashimoto's thyroiditis (HT), atrophic autoimmune thyroiditis, postpartum thyroiditis, painless thyroiditis unrelated to pregnancy and thyroid-associated ophthalmopathy. This spectrum present contrasts in terms of thyroid function, disease duration and spread to other anatomic location. The genetic basis of autoimmune thyroid disease (AITD) is complex and likely to be due to genes of both large and small effects. In GD the autoimmune process results in the production of thyroid-stimulating antibodies and lead to hyperthyroidism, whereas in HT the end result is destruction of thyroid cells and hypothyroidism. Recent studies in the field of autoimmune thyroid diseases have largely focused on (i) the genes involved in immune response and/or thyroid physiology with could influence susceptibility to disease, (ii) the delineation of B-cell autoepitopes recognized by the main autoantigens, thyroglobulin, thyroperoxidase and TSH receptor, to improve our understanding of how these molecules are seen by the immune system and (iii) the regulatory network controlling the synthesis of thyroid hormones and its dysfunction in AITD. The aim of the present review is to summarize the current knowledge regarding the relation existing between some susceptibility genes, autoantigens and dysfunction of thyroid function during AITD.

Role of apoptosis in pathogenesis of thyroiditis

Apoptosis is a highly regulated mechanism of cell death that differs from necrosis and plays an important role in normal tissue development, homeostasis and immune regulation. Apoptosis is involved in many diseases. Defective apoptosis can cause systemic autoimmunity by allowing the survival of autoreactive lymphocytes. It may also be involved in the pathogenesis of organ-specific autoimmune diseases such as Hashimoto's thyroiditis and in the pathogenesis of tumors. Apoptosis is regulated at multiple levels, including death receptor and ligand expression, adapter protein, cascades of caspases, mitochondria and the expression of anti apoptotic and pro apoptotic proteins. Apoptotic cell death can occur by two different pathways. Type I is initiated by the activation of death receptors (Fas, TNF-receptor-family) on the plasma membrane followed by activation of caspase 8. Type II involves changes in mitochondrial integrity initiated by various effectors, leading to the release of cytochrome c and activation of caspase 9. The thyroid cell destruction characteristic of autoimmune thyroiditis can be seen as the consequence of inappropriate expression of Fas or TRAIL death pathway molecules and down-regulation of the apoptosis controlling protein Bcl-2, which may be induced by cytokines released locally by infiltrating lymphocytes. Thyroid cell destruction in autoimmune hypothyroidism is dependent on T cell-mediated cytotoxicity with the likely additional effect of death receptor-mediated apoptosis. Modulation of apoptosis-related proteins by T helper 1 and T helper 2 cytokines controls thyrocyte survival in thyroid autoimmunity.

Proposing a causal link between thyroid hormone resistance and primary autoimmune hypothyroidism

Resistance to thyroid hormone (RTH) is a rare, inherited condition. It is characterised by raised circulating fT4 and TSH levels. The literature contains a number of descriptions of the finding of thyroid autoantibodies in patients with RTH. Until now, this has been attributed to the coincidental development of primary autoimmune thyroiditis as a second unrelated pathology. Our hypothesis is that the chronic TSH elevation in RTH stimulates lymphocytes to produce the pro-inflammatory cytokine TNF-alpha. TNF-alpha, in turn mediates thyroid cell destruction by binding to its receptors on thyrocytes, or indirectly by potentiating antibody formation or cytotoxic T lymphocyte production.

The Role of Stress in the Clinical Expression of Thyroid Autoimmunity

During stress, activation of the hypothalamic-pituitary-adrenal axis and the sympathoadrenal system leads to increased secretion of glucocorticoids and catecholamines, respectively, in order to maintain homeostasis. Recent evidence suggests that stress hormones, acting on antigen-presenting immune cells, may influence the differentiation of bipotential T helper (Th) cells away from Th1 and toward a Th2 phenotype. This results in suppression of cellular immunity and potentiation of humoral immunity. Thyroid autoimmunity is clinically expressed as Hashimoto's thyroiditis (HT) and its variants (sporadic or postpartum thyroiditis) or as Grave's disease (GD). The different phenotypic expression of thyroid autoimmunity is largely dependent on the balance of Th1 versus Th2 immune response. A predominantly Th1-mediated immune activity may promote apoptotic pathways on thyroid follicular cells leading to thyroid cell destruction and HT. Conversely, predominance of Th2-mediated immune response may induce antigen-specific B lymphocytes to produce anti-TSH receptor (TSHr) antibodies causing GD. The weight of evidence from epidemiological and case-control studies supports an association between stress and GD. On the other hand, there is little information available on the effect of stress on HT, but there is evidence for an increase in postpartum thyroiditis, following the cellular immune suppressive effect of pregnancy. Whether stress has a causative effect on GD remains elusive. Circumstantial evidence supports the hypothesis that stress may influence the clinical expression of thyroid autoimmunity in susceptible individuals favoring the development of GD by shifting the Th1-Th2 balance away for Th1 and toward Th2. Conversely, recovery from stress or the immune suppressive effect of pregnancy may induce a Th2 to Th1 "return shift" leading to autoimmune (sporadic) or postpartum thyroiditis, respectively.

Pituitary, adrenal and thyroid dysfunction

Regulation of the adrenal and thyroid glands by the hypothalamo-pituitary axis depends on feedback loops. A breakdown in this feedback system may lead to chronic stimulation or inhibition and endocrine disorders. The adrenal gland secretes steroids (mineralocorticoids, glucocorticoids and androgens) and catecholamines. Adrenal insufficiency (Addison’s disease) is an autoimmune condition that results in the destruction of the adrenal glands. Treatment is by replacement of glucocorticoids and mineralocorticoids. Primary hyperaldosteronism (Conn’s syndrome) and Cushing’s syndrome arise through mineralocorticoid and glucocorticoid secreting tumours, respectively. Both are treated by surgery where possible. Pharmacological management is by inhibitors of dehydrogenation (trilostane) and hydroxylation (metyrapone) in the steroidogenic pathway. Tumours of the adrenal medulla (phaeochromocytoma) require alpha- and beta-blocker treatment to lower blood pressure (phenoxybenzamine) and reduce tachycardia (propanolol) before surgical removal. The thyroid gland secretes triiodothyronine (T3) and thyroxine (T4). Hypothyroidism arises through iodine deficiency, autoimmunity or surgery: treatment is by replacement of T3 and T4. Hyperthyroidism is also an autoimmune disease, commonly Graves’ disease. Treatment is by selective destruction of thyroid cells by radioiodine. Alternatively thioureylenes (carbimazole) are used to inhibit iodination of thyroglobulin, thereby reducing T3 and T4 synthesis. The parathyroid gland contributes to serum calcium homeostasis by secreting parathyroid hormone. Hyperparathyroidism leads to hypercalcaemia, which is reversed by surgery or calcitonin treatment. Hypercalcaemia of malignancy is managed by bisphosphonates, which reduce bone turnover. Hypoparathyroidism and vitamin D deficiency lead to hypocalcaemia, which is treated by calcium and vitamin D metabolite replacement.

Autoimmune thyroid disorders—An update

Autoimmune thyroid disease (AITD), a common organ specific autoimmune disorder is seen mostly in women between 30-50 yrs of age. Thyroid autoimmunity can cause several forms of thyroiditis ranging from hypothyroidism (Hashimoto's thyroiditis) to hyperthyroidism (Graves'Disease). Prevalence rate of autoimmune mediated hypothyroidism is about 0.8 per 100 and 95% among them are women. Graves' disease is about one tenth as common as hypothyroidism and tends to occur more in younger individuals. Both these disorders share many immunologic features and the disease may progress from one state to other as the autoimmune process changes. Genetic, environmental and endogenous factors are responsible for initiation of thyroid autoimmunity. At present the only confirmed genetic factor lies in HLA complex (HLA DR-3) and the T cell regulatory gene (CTLA 4). A number of environmental factors like viral infection, smoking, stress & iodine intake are associated with the disease progression. The development of antibodies to thyroid peroxidase (TPO) thyroglobulin (TG) and Thyroid stimulating hormone receptor (TSH R) is the main hallmark of AITD. Circulating T Lymphocytes are increased in AITD and thyroid gland is infiltrated with CD4+ and CD8+ T Cells. Wide varieties of cytokines are produced by infiltrated immune cells, which mediate cytotoxicity leading to thyroid cell destruction. Circulating antibodies to TPO and TG are measured by immunofluorescense, hemagglutination, ELISA & RIA. TSHR antibodies of Graves' disease can be measured in bioassays or indirectly in assays that detect antibody binding to the receptor.

Cellular immune responses in autoimmune thyroid disease.

Recent research in autoimmune thyroid disease (AITD) has largely focused on delineation of the autoantigens and their epitopes, but there is now renewed interest in the immunoregulatory properties of T cells, an understanding of which may explain the emergence of AITD in experimental settings. T cell recognition of autoantigens has shown considerable intra- and interindividual heterogeneity, and a mixed pattern of cytokine production indicates that both the Th1 and Th2 limbs of the helper T cell response are involved in all types of AITD. It is now clear that secretion of chemokines and cytokines within the thyroid accounts for the accumulation and expansion of the intrathyroidal lymphocyte pool, and that the thyroid cells themselves contribute to this secretion. The thyroid cells also produce a number of proinflammatory molecules which will tend to exacerbate the autoimmune process. Thyroid cell destruction in autoimmune hypothyroidism is dependent on T cell-mediated cytotoxicity with the likely additional effect of death receptor-mediated apoptosis.