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Thyroid Autoimmune Disease
Abstract
Autoimmune diseases are a group of disorders in which the immune system dysfunctions and attacks host tissues. Although the pathogenesis of autoimmune thyroid disease has not been elucidated, there are several factors that have been associated with the disorder.
Factors include genetic predisposition, nutrient deficiencies, use of certain medications affecting thyroid function, and environmental factors including exposure to radiation, heavy metals, and chemical contaminants. Thyroid disorders are often treated with drug therapy, which often have
serious side effects and do not necessarily treat the underlying condition leading to the thyroid dysfunction. In recent years there has been increased interest in herbs and supplements as individuals take more interest in their health and well being. For autoimmune disease, vitamin D supplementation
is recommended as deficiency in this nutrient has been associated with the disorder. Additionally, it also modulates T cell response and inhibits Th1 cytokines. In cases of autoimmune hyperthyroid disorder, rosmarinic acid, selenium and iodide supplementation are recommended. For autoimmune
hypothyroid disorder, blue flag (Iris versicolor) and guggul (Commiphora mukul), selenium and iodide supplementation are indicated. Each of these supplements plays a specific role in restoring normal thyroid function. Further, rosmarinic acid found in plants such as rosemary
(Rosmarinus officinalis), bugleweed (Lycopus virginicus), and lemon balm (Melissa officinalis) also calms excess T cell activity and pro inflammatory cytokine release. The use of these combinations of supplements should restore thyroid hormone homeostasis in autoimmune
thyroid disorders. Proper medical supervision is required to ensure these herbs and nutrients are used safely and potential adverse effects are avoided.
... Poza tym odgrywają istotną rolę w pobudzaniu mięśnia sercowego oraz pracy układu nerwowego i mózgu. 1 Wpływają na funkcjonowanie większości tkanek organizmu i charakteryzują się najszerszym spektrum działania spośród poznanych hormonów. 2 Tarczyca jest odpowiedzialna za około 30% spoczynkowej przemiany materii, dlatego przy niedoborze hormonów tarczycy dostarczana z pożywieniem energia jest magazynowana w postaci tkanki tłuszczowej, co prowadzi do nadwagi i otyłości. ...
... Jej przyczyny to np. infekcje wirusowe czy niedobór jodu w pożywieniu, może być też wrodzona, jednak najczęstszym powodem hipotyreozy jest choroba Hashimoto. 1 Autoimmunologiczne zapalenie tarczycy (choroba Hashimoto) jest chorobą, w której układ immunologiczny produkuje przeciwciała przeciwko peroksydazie tarczycowej (anty-TPO) i przeciw tyreoglobulinie (anty-TG). Prowadzi to do powstania nacieków limfocytarnych na tarczycy oraz zaniku komórek pęcherzykowych gruczołu. ...
... Wiadomo, że wysiłek wpływa na stężenie trójjodotyroniny, ale nie tyroksyny. 1 Podaż białka u osób cierpiących na chorobę Hashimoto powinna być większa niż u zdrowych ludzi. Najlepiej, aby jego źródłem były produkty pochodzenia zwierzęcego, zawierające pełnowartościowe białko. ...
... 12 Researchers in cross-sectional studies reported that patients with nodular goiters often have an increase in thyroid antibodies, which is more common in iodine deficiency. 4,21 These observations suggest that immune stimulation to thyroid proteins occurs during iodine deficiency and may be a causative factor in the development of thyroid autoimmunity. ...
... 16 On the basis of data derived from the National Health and Nutrition Examination Survey, although iodine intake in the United States continues to decrease, the prevalence of AIT continues to increase. 21,30,31 This correlation suggests that iodine deficiency may be a causative factor in patients with AIT. ...
... Environmental factors, such as exposure to radiation, heavy metals, chemical contaminants, halogens, infectious disease, drugs, and selenium deficiency, are also implicated in thyroid autoimmunity. 5,7,21 Environmental interactions have been shown to influence oxidative stress, thyroid antigens, and antibody production and may also contribute to iodine deficiency. Chemicals such as bromine, choline, and polychlorinated biphenyls have been shown to competitively inhibit iodide uptake by the NIS and cause oxidative damage. ...
... In particular, mercury and cadmium have demonstrated an ability to negatively impact thyroid health. 27 Cadmium has a complex array of effects on thyroid function, including decreased secretion of T4 by thyroid follicular cells, and altered peripheral conversion of T4 to T3 by deiodinase enzymes. 28,29 Selenium plays an important role in reducing cadmium levels by binding to cadmium and facilitating its excretion through bile. ...
... 28,29 Selenium plays an important role in reducing cadmium levels by binding to cadmium and facilitating its excretion through bile. 27 Elevated mercury levels have been linked to increased Tg levels, with mechanistic data demonstrating that inorganic mercury affects thyroid peroxidase (TPO) and both inorganic as well as organic mercury inhibit thyroglobulin iodination. 30,31 Selenium has an antagonistic relationship with mercury, demonstrating a protective effect when mercury levels are elevated. ...
... Zinc, vitamin D, vitamin A, and most importantly iodine, play crucial roles in thyroid hormone production and subsequent thyroid health. 27,33 The roles of zinc, vitamin D, and vitamin A in thyroid function are beyond the scope of this review, but the complex interaction and codependence between iodine and selenium warrants discussion ( Figure 1). ...
Autoimmune thyroid diseases, including Graves’ disease and Hashimoto’s thyroiditis, are the most common autoimmune conditions in humans. There is significant morbidity associated with thyroid autoimmunity, and typically ongoing management is required to control disease presentation and reduce sequelae. Thyroid tissues contain the highest concentration of selenium in the body, owing to selenium’s crucial role in glutathione peroxidases, thioredoxin reductases, and iodothryonine deiodinases. Selenium deficiency is associated with sub-optimal thyroid function, and has been shown to be a risk factor for both Hashimoto’s thyroiditis and Graves’ disease. As a therapeutic intervention, selenium has been shown in a number of studies to reduce thyroid antibodies, although there remains limited information regarding its impact on clinical outcomes. In Graves’ disease, and specifically in Graves’ ophthalmopathy, selenium appears to play a beneficial role in altering disease progression and improving ophthalmic symptoms. The various functions of selenium in thyroid autoimmunity are reviewed.
... Both these illness are metabolic disarranges emerging due to dishonorable life fashion. (2,3) Thyroid clutter can happen from somewhat broaden of thyroid organ, this sort of clutter no have to be treatment, for long life thyroid cancer. The foremost common causes of thyroid clutter are irregular development of thyroid hormones [4,5]. ...
... Essential hypothyroidism implies the inside movement of thyroid organ, driving to diminish circulation of thyroid hormones or disappointment to deliver sufficient thyroid hormone and auxiliary hypothyroidism alludes as typical pituitary invigorate by hypothalamic TSH-releasing hormone. [3][4][5][6] The most causes of hypothyroidism are taking after as: 1) Brokenness of thyroid organ 2) Need of TRH, (hypothalamic TSH-releasing hormone) and TSH (thyroid invigorating hormone), or both 3) Lacking nourishment of iodine count calories. [6] Hyperthyroidism Hyperthyroidism implies rise of thyroid work. ...
... Both these disease are metabolic disorders arising due to improper life style. [2,3] Thyroid disorder can occur from slightly enlarge of thyroid gland, this type of disorder no need to treatment, for long life thyroid cancer. The most common causes of thyroid disorder are abnormal growth of thyroid hormones [4,5]. ...
... Primary hypothyroidism means the internal activity of thyroid gland, leading to decrease circulation of thyroid hormones or failure to produce enough thyroid hormone and secondary hypothyroidism refers as normal pituitary stimulate by hypothalamic TSH-releasing hormone. [3][4][5][6] The main causes of hypothyroidism are following as: 1) Dysfunction of thyroid gland 2) Lack of TRH, (hypothalamic TSH-releasing hormone) and TSH (thyroid stimulating hormone), or both 3) Inadequate nutrition of iodine diet. [6] Hyperthyroidism Hyperthyroidism means elevation of thyroid function. ...
Herbal drugs have proven to be useful in number of diseases. Metabolic disorders are some disorders which progress at a slower rate but damage the whole functioning of the body. Conventional drugs available for these disorders cure symptomatically. Herbal drugs have the capacity to cure such metabolic disorders synergistically at different steps. The objective of this review lies in summarizing different herbal drugs that can be used for treating thyroid and related disorders effectively.
... Lack of iodine is widespread in modern dietary and lifestyle. High dietary perchlorate, glucosinolate, thiocyanate, calcium nitrate, cobalt and rubidium interfere with iodine metabolism and may increase iodine requirements [64,65]. Household hygiene products such as chlorine containing beach and fluoride in water and toothpaste further depletes iodine in our body. ...
The pandemic of novel coronavirus caused COVID-19 had resulted in a high number of hospitalizations and deaths and caused a devastating toll on human and society health. The symptoms of the infected patients vary significantly, from life-threatening to mild or even asymptomatic. This clinical observation led to hypothesize on the critical role of host innate immunity in the disease development and progression. As the first defense barrier against microorganisms, the innate immune reaction determines not only the viral infection rate but also immune-mediated response. Therefore, promote healthy behaviors to enhance innate immunity with functional food and nutritional agents may be a rational strategy for minimizing damages caused by viruses to global health.
... They act as regulator of heart rate, body temperature, and cholesterol and body weight [2]. Hypothyroidism means defect in thyroid gland function [3] and can be classified into :firstly Primary hypothyroidism which is due to thyroid gland disorder leading to decreased circulation of thyroid hormones or failure to produce enough thyroid hormone and the second type is called secondary hypothyroidism that caused by a disorder of the pituitary gland or the hypothalamus axis which lead to decreased TSH synthesis and then to decreased synthesis and secretion of thyroid hormones [4]. ...
This study was conducted to demonstrate the role of methanolic extract from Ficuscarica leaves in the treatment of hypothyroidism disease which induced in male rats by carbimazole drug. Forty male rats were divided into five groups, eight for each. group I selected as a negative control which primed orally with normal saline alone, group II served as a positive control and treated by carbimazole anti-thyroid drug for six weeks ,while group III was treated by plant extract (500 mg /kg, bw) for six weeks ,whereas the fourth group IV was treated by carbimazole drug (5 mg) for six weeks to induce hypothyroidism and then treated by plant extract (500 mg /kg , bw) for six weeks too. Finally the fifth V group was treated by thyroxin drug (100 mg) for six week instead of plant extract.The results showed that a non-significant difference (P< 0.05) in the level of IL-2 of the fourth group when compared with the first group , while the results revealed a significant increase when compared with the second group ,whereas a significance decrease when compared with the third and fifth groups. The immunohistochemical sections of rats thyroid gland in the first , second and third groups revealed that weak expression of IL-2 immunopositive cells (brown cytoplasmic deposits) in thyroid sections, while rats thyroid gland in the fourth group and fifth groups revealed that a moderate expression of IL-2 immunopositive cells. In conclusion it is possible to use methanolic extract of Ficuscarica leaves in the regulation of immune response in hypothyroidism disease may due to the presence of phytochemical components that enhance the cellular immune response by increase the IL-2 production.
... Hypothyroidism means suppression of thyroid function [3] and can be divided into :firstly Primary hypothyroidism which is due to thyroid gland disorder leading to decreased circulation of thyroid hormones or failure to produce enough thyroid hormone and the second type is called secondary hypothyroidism that caused by a disorder of the pituitary gland or the hypothalamus axis which lead to decreased TSH synthesis and then to decreased synthesisand secretion of thyroid hormones. [4]. Hypothyroidism disease are diagnosed by low level of (T4) and (T3) and high level of thyroid-stimulating hormone (TSH) [5]. ...
This study was conducted to demonstrate the role of alcoholic extract from ficus carica leaves in the treatment of hypothyroidism disease which induced by carbimazole drug. Forty male rats were divided into five groups, eight for each. group I selected as negative control and administered orally with normal saline alone, group II served as positive control and treated by carbimazole anti-thyroid drug for six weeks , group III was treated by plant extract (500 mg /kg, bw) for six weeks, the fourth group IV was treated by carbimazole drug (5 mg) for six week to induce hypothyroidism and then treated by plant extract (500 mg /kg , bw) , and the fifth V group was treated by thyroxin drug (100 mg) for six week instead of plant extract. The results showed insignificant differences (P<0.05) in body weight gain in the fourth group (carbimazole and plant extract) when compared with the first group (normal saline alone), second group (carbimazole alone), third group (plant extract alone , while the results demonstrated that a significant increase (P<0.05) in body weight gain when compared with fifth groups (carbimazole and thyroxine). While the results revealed insignificant differences (P<0.05) in the concentrations of T3 and T4 in the fourth (carbimazole & plant extract), fifth groups (carbimazole & thyroxin drug) and the third group (plant extract alone) when compared with the first group (normal saline alone), but there was a significant increase (P<0.05) when compared with the second group (carbimazole alone) , in addition the results indicated a significant decrease (P<0.05) when compared with the third group, Furthermore, the results revealed insignificant difference (P<0.05) in TSH concentration in the fourth (carbimazole & plant extract), fifth groups (carbimazole & thyroxin drug) and the third group (plant extract alone) when compared with the first group (normal saline alone) , also the data showed a significant decrease(P<0.05) when compared with the second group (carbimazole alone). In conclusion, it is possible to use methanolic plant extract from ficus carica leaves in the regulation of hypothyroidism due to the presence of phytochemical components that can be affect the mechanism of T3 and T4 production by the thyroid gland.
... They act as regulator of heart rate, body temperature, and cholesterol and body weight [2]. Hypothyroidism means defect in thyroid gland function [3] and can be classified into :firstly Primary hypothyroidism which is due to thyroid gland disorder leading to decreased circulation of thyroid hormones or failure to produce enough thyroid hormone and the second type is called secondary hypothyroidism that caused by a disorder of the pituitary gland or the hypothalamus axis which lead to decreased TSH synthesis and then to decreased synthesis and secretion of thyroid hormones [4]. ...
This study was conducted to demonstrate the role of methanolic extract from Ficuscarica leaves in the treatment of hypothyroidism disease which induced in male rats by carbimazole drug. Forty male rats were divided into five groups, eight for each. group I selected as a negative control which primed orally with normal saline alone, group II served as a positive control and treated by carbimazole anti-thyroid drug for six weeks ,while group III was treated by plant extract (500 mg /kg, bw) for six weeks ,whereas the fourth group IV was treated by carbimazole drug (5 mg) for six weeks to induce hypothyroidism and then treated by plant extract (500 mg /kg , bw) for six weeks too. Finally the fifth V group was treated by thyroxin drug (100 mg) for six week instead of plant extract.The results showed that a non-significant difference (P< 0.05) in the level of IL-2 of the fourth group when compared with the first group , while the results revealed a significant increase when compared with the second group ,whereas a significance decrease when compared with the third and fifth groups. The immunohistochemical sections of rats thyroid gland in the first , second and third groups revealed that weak expression of IL-2 immunopositive cells (brown cytoplasmic deposits) in thyroid sections, while rats thyroid gland in the fourth group and fifth groups revealed that a moderate expression of IL-2 immunopositive cells. In conclusion it is possible to use methanolic extract of Ficuscarica leaves in the regulation of immune response in hypothyroidism disease may due to the presence of phytochemical components that enhance the cellular immune response by increase the IL-2 production.
The purpose of this study was to determine the effects of a guggulsterone phosphate salt compound on body composition and mood states in overweight adults. In a double-masked, randomized, placebo-controlled study, 20 subjects with a body-mass index >25 kg/m2 were separated into 1 of 3 groups. The experimental group received guggulsterones 750 mg and phosphate 1650 mg daily, the placebo group received maltodextrin capsules, and the control group received no treatment for 6 weeks. Subjects were instructed to follow the American Heart Association Step One diet and a 3-day-per-week circuit exercise program. Body weight decreased significantly in the experimental group (3.2%, P < 0.05) and fat mass decreased significantly in the experimental (20.6%) and control (8.6%) groups (P < 0.01). However, between-group differences in weight loss were not statistically significant. Profile of Mood States (POMS)-fatigue decreased significantly in the experimental group (63.7%, P < 0.01), whereas POMS-vigor increased significantly in the experimental group (32.3%, P < 0.01) and decreased significantly in the placebo group (15.6%, P < 0.01). Results of this study suggest that ingestion of a guggulsterone phosphate salt compound concurrent with regular exercise will result in a significant loss of body weight and improved mood states.
The results of this study indicate that melatonin induces hypothyroidism in mice within eight days. Simultaneous administration of melatonin and petroleum ether extract of Commiphora mukul brings about a significant improvement in thyroid structure and function. Further, melatonin induced hypothyroidism is although a little reversible yet it is normalized quickly after C. mukul treatment. These data suggest that C. mukul directly stimulates thyroid function probably through some enzymatic mechanisms.
Thyroid disorders are prevalent and their manifestations are determined by the dietary iodine availability.
Data from screening large population samples from USA and Europe.
The most common cause of thyroid disorders worldwide is iodine deficiency, leading to goitre formation and hypothyroidism. In iodine-replete areas, most persons with thyroid disorders have autoimmune disease.
Definition of thyroid disorders, selection criteria used, influence of age and sex, environmental factors and the different techniques used for assessment of thyroid function.
Increasing incidence of well-differentiated thyroid cancer. Environmental iodine influences the epidemiology of non-malignant thyroid disease.
Iodine supplementation of populations with mild-to-moderate iodine deficiency. An evidence-based strategy for the risk stratification, treatment and follow-up of benign nodular thyroid disease. Is there any benefit in screening adults for thyroid dysfunction?
The role of vitamin D as an immune modulator has been emphasized in recent years, and low levels of the hormone were observed in several autoimmune diseases including multiple sclerosis and systemic lupus erythematosus. Vitamin D mediates its effect though binding to vitamin D receptor (VDR), and activation of VDR-responsive genes. While VDR gene polymorphism was found to associate with autoimmune thyroid diseases (AITDs), few studies examined levels of vitamin D in these patients and those that did yielded conflicting results. We therefore undertook to evaluate the levels of vitamin D in patients with AITDs compared to patients with non-AITDs and healthy controls. Serum vitamin D (25-OH) levels were measured in 50 patients with AITDs, 42 patients with non-AITDs and 98 healthy subjects, utilizing the LIAISON chemiluminescence immunoassay (DiaSorin, Saluggia, Italy). Vitamin D deficiency was designated at levels lower than 10 ng/ml. Antithyroid antibodies, thyroid functions and demographic parameters were evaluated in all patients. The prevalence of vitamin D deficiency was significantly higher in patients with AITDs compared with healthy individuals (72% versus 30.6%; P<0.001), as well as in patients with Hashimoto's thyroiditis compared to patients with non-AITDs (79% versus 52%; P<0.05). Vitamin D deficiency also correlated to the presence of antithyroid antibodies (P=0.01) and abnormal thyroid function tests (P=0.059). Significantly low levels of vitamin D were documented in patients with AITDs that were related to the presence of anti thyroid antibodies and abnormal thyroid function tests, suggesting the involvement of vitamin D in the pathogenesis of AITDs and the advisability of supplementation.
Retinoic acid (RA) and thyroid hormone are critical for differentiation and organogenesis in the embryo. Mct8 (monocarboxylate
transporter 8), expressed predominantly in the brain and placenta, mediates thyroid hormone uptake from the circulation and
is required for normal neural development. RA induces differentiation of F9 mouse teratocarcinoma cells toward neurons as
well as extraembryonal endoderm. We hypothesized that Mct8 is functionally expressed in F9 cells and induced by RA. All-trans-RA (tRA) and other RA receptor (RAR) agonists dramatically (>300-fold) induced Mct8. tRA treatment significantly increased uptake of triiodothyronine and thyroxine (4.1- and 4.3-fold, respectively), which
was abolished by a selective Mct8 inhibitor, bromosulfophthalein. Sequence inspection of the Mct8 promoter region and 5′-rapid amplification of cDNA ends PCR analysis in F9 cells identified 11 transcription start sites
and a proximal Sp1 site but no TATA box. tRA significantly enhanced Mct8 promoter activity through a consensus RA-responsive element located 6.6 kilobases upstream of the coding region. A chromatin
immunoprecipitation assay demonstrated binding of RAR and retinoid X receptor to the RA response element. The promotion of
thyroid hormone uptake through the transcriptional up-regulation of Mct8 by RAR is likely to be important for extraembryonic endoderm development and neural differentiation. This finding demonstrates
cross-talk between RA signaling and thyroid hormone signaling in early development at the level of the thyroid hormone transporter.
Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy.
Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women.
We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation.
Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (ΣPBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), -20.6 to 0.0] and 18.7% (95% CI, -29.2 to -4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ΣPBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ΣPBDEs.
Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.
All organisms must maintain a complex dynamic equilibrium, or homeostasis, which is constantly challenged by internal or external adverse forces termed stressors. Stress occurs when homeostasis is threatened or perceived to be so; homeostasis is re-established by various physiological and behavioral adaptive responses. Neuroendocrine hormones have major roles in the regulation of both basal homeostasis and responses to threats, and are involved in the pathogenesis of diseases characterized by dyshomeostasis or cacostasis. The stress response is mediated by the stress system, partly located in the central nervous system and partly in peripheral organs. The central, greatly interconnected effectors of this system include the hypothalamic hormones arginine vasopressin, corticotropin-releasing hormone and pro-opiomelanocortin-derived peptides, and the locus ceruleus and autonomic norepinephrine centers in the brainstem. Targets of these effectors include the executive and/or cognitive, reward and fear systems, the wake-sleep centers of the brain, the growth, reproductive and thyroid hormone axes, and the gastrointestinal, cardiorespiratory, metabolic, and immune systems. Optimal basal activity and responsiveness of the stress system is essential for a sense of well-being, successful performance of tasks, and appropriate social interactions. By contrast, excessive or inadequate basal activity and responsiveness of this system might impair development, growth and body composition, and lead to a host of behavioral and somatic pathological conditions.
1 Brassica vegetables are the major source of glucosinolates in the human diet. Certain glucosinolates are readily converted into goitrogenic species, notably 5-vinyloxazolidine-2-thione and thiocyanate ion. The effect of dietary Brussels sprouts, a particularly rich source of such glucosinolates, on thyroid function has been examined.
2 Inclusion of cooked Brussels sprouts (150 g daily for 4 weeks) into a normal diet of 10 volunteer subjects had no effect on thyroid function as determined by measurement of thyrotrophic hormone, thyroxine and tri-iodothyronine even though the sprouts contained high concentrations (220 mg/100 g) of glucosinolates.
3 In view of the reported antithyroid activity of 5-vinyloxazolidine-2-thione it is suggested that this lack of activity of cooked Brussels sprouts is due to inactivation during cooking of myrosinase, the specific glucosinolate-degrading enzyme.
Serum levels of hydrocortisone, T4, T3 and rT3 were estimated before and after exercise. In group A, untrained young subjects had to cope with a submaximal, fractionated load on a bicycle ergometer. T3 increased, rT3 and cortisol decreased, T4 remained unchanged. Sportsmen in group B accomplished a 10 or 15 km run as a part of their regular training. A rise of cortisol and rT3 was observed, T3 remained unchanged and T4 decreased. In better trained sportsmen the initial level of serum T3 exceeded the upper border of normal values (3.3 nmol/l) and the terminal values of cortisol reached a higher value than in the less trained subjects. It is suggested that the mobilization of fuel from energy stores and the oxidative processes are better regulated in trained sportsmen than in untrained subjects. A sign of the best adjustment to a long run was accompanied by an initial serum T3 above the normal borderline and by a great increase of cortisol after the run.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2-D3] is known to be an immunosuppressive hormone. This review primarily deals with in vitro and in vivo effects of 1,25-(OH)2-D3 and analogue, 1,25-dihydroxy-16ene-vitamin D3 [1,25-(OH)2-16ene-D3], on T helper subsets type 1 (Th1) or type 2 (Th2) that have distinctive functional characteristics in humans. Th1 secrete interferon (IFN-gamma), interleukin (IL-2) and induce B cells to produce immunoglobulin IgG2a while Th2 secrete IL-4, IL-10 and induce the production of IgG1 and IgE by B cells. The sterol inhibits the secretion of IL-12, a cytokine produced by monocytes and B cells, which leads to the activation and differentiation of Th1. In addition, 1,25-(OH)2-D3 directly inhibits IFN-gamma secretion by Th1 clones while it has little effect on IL-4 secretion by Th2 clones. The analogue, 1,25-(OH)2-16ene-D3, is 100-fold more potent than 1,25-(OH)2-D3 in inhibiting IFN-gamma secretion but also has little effect on IL-4 secretion. In mice, when given in vivo, the sterol prevents the induction of spontaneous and induced autoimmune diseases and inhibits Th1 induce IgG2a responses. These actions of the vitamin D3 compounds suggest that it may have potential therapeutic applications in Th1-mediated clinical situations such as autoimmunity and transplantation.
Barnes, et al, estimate that 40% of the American population suffer from thyroid dysfunction and that hypothyroidism is the most common complaint seen by doctors in this country. 1 Several factors contribute to clinical thyroid dysfunction such as diseases affecting the gland itself or a disturbance in the hypothalamic — pituitary — thyroid axis. Subclinical thyroid dysfunction particularly, hypothyroidism, is more common than clinical pathology of the thyroid gland. Subclinical hypothyroidism can produce or contribute to an array of metabolic dysfunctions and symptoms that may respond readily to a conservative nutritional approach. Conditions Associated with Hypothyroidism Severe clinical thyroid insufficiency is associated with many conditions including myxedema, cretinism in children, goiter, arteriosclerosis, and hyperlipidemia. 2 Subclinical hypothyroidism is more common and is not always easily detectable through normal testing procedures. Subclinical hypothyroidism could be described as a syndrome rather than a disease and is characterized by fatigue, depression, cold sensitivity, and changes in the skin and hair texture. The development of fatigue is usually insidious, resulting in the requirement of extra sleep. Depression may develop often and become more prolonged with each episode. Cold sensitivity first develops in the extremities. Cold hands and feet may become present even in the summer. The skin becomes dryer, and the hair may become coarse or thin, with accompanying hair loss. Nutritional Deficiency and Hypothyroidism A number of nutritional deficiencies are known to develop in subclinical hypothyroidism. The most recognized is iron deficiency.
The antihormonal activity of Lithospermum officinale (Boraginaceae) and Lycopus virginicus and other Lamiaceae has been investigated in the rat. L. officinale cold water freeze dried extracts (FDE) significantly lowered thyroid hormone content in the serum whereas an inactivated extract exhibited a considerable loss of biological activity. The efficacy of different plant extracts greatly depended on the extraction procedure: extraction of powdered leaves with boiling water or ethanol yielded FDEs without thyroid hormone-lowering capacity. The chemical oxidation of a hot-water (100°C) extract by KMnO4 served to reintroduce the antihormonal effectiveness. In a goiter suppression test, the chronic administration of L. officinale FDE greatly suppressed TSH-levels and consequently goiter weight. The antithyrotropic and antithyroidal activity of a variety of plant extracts was accompanied by an additional prolactin diminution. Lithospermum officinale exhibited a strong antigonadotropic effectiveness and completely inhibited the PMS-stimulated growth of ovaries and uteri by as little as 100 μg of FDE. As to the mechanism of action there are different possibilities:
1. inactivation of the circulating hormone (TSH, Prolactin, PMS), the so-called hypophysealhormone-blocking effect.
2. inhibition of hypophyseal hormone secretion (TSH, Prolactin).
3. inhibition of thyroidal secretion (T4 and T3).
These clinical practice guidelines summarize the recommendations of the American Association of Clinical Endocrinologists for the diagnostic evaluation of hyperthyroidism and hypothyroidism and for treatment strategies in patients with these disorders. The sensitive thyroid-stimulating hormone (TSH or thyrotropin) assay has become the single best screening test for hyperthyroidism and hypothyroidism, and in most outpatient clinical situations, the serum TSH is the most sensitive test for detecting mild thyroid hormone excess or deficiency. Therapeutic options for patients with Graves' disease include thyroidectomy (rarely used now in the United States), antithyroid drugs (frequently associated with relapses), and radioactive iodine (currently the treatment of choice). In clinical hypothyroidism, the standard treatment is levothyroxine replacement, which must be tailored to the individual patient. Awareness of subclinical thyroid disease, which often remains undiagnosed, is emphasized, as is a system of care that incorporates regular follow-up surveillance by one physician as well as education and involvement of the patient.
The thyroid gland is the most common organ affected by autoimmune disease. Other autoimmune diseases, most notably type 1 diabetes mellitus, are increasing in incidence. It is unknown whether autoimmune thyroid diseases are following the same pattern. This review summarizes studies of autoimmune thyroid disease incidence and prevalence since 1950, not only for these measures of occurrences, but also for commenting on identified risk factors for thyroid autoimmunity. We find that incidence of autoimmune thyroid disease is currently higher than in historic series although the studies are so variable in design, patient population, disease definition, and laboratory methods that it is impossible to tell whether this difference is real. Further research is required to assess the possibility of changing disease patterns of autoimmune thyroid disease as opposed to simple changes in diagnostic thresholds.
In this paper, it is demonstrated that many steps in the food production chain of vegetable products can have large influence on the final intake of health protective phytochemicals. The wide variations in levels at each step in the production chain makes an experimental quantification of the dietary intake of phytochemical extremely difficult. We present a concept for predictive modelling of the effects of various processes in the production chain of vegetable products on the intake of phytochemicals with potential health benefits. This approach is intended to be used for the developments of tools to facilitate both product and process development for health products as well as epidemiological input data for bioactive substances in the diet. Protective glucosinolates present in Brassica vegetables are used to illustrate the value of such a predictive model. The described model provides a powerful tool for handling the variation of glucosinolate levels throughout the chain in a quantitative way. Product development, consumer advice and human intervention trials are important areas that could benefit enormously from this approach.
Associations between positive thyroid autoantibodies and total blood mercury in women were evaluated using the National Health and Nutrition Examination Survey (NHANES), 2007-2008. Women are at increased risk for autoimmune disorders, mercury exposure has been associated with cellular autoimmunity and mercury accumulates in the thyroid gland. We used multiple logistic regression to evaluate the associations between total bloodmercury and thyroglobulin autoantibody antibody positivity and thyroid peroxidase autoantibody positivity in non-pregnant, non-lactating women aged 20 and older not currently using birth control pills or other hormone therapies, adjusted for demographic factors, menopausal status, nutrient intake and urine iodine (n=2047). Relative to women with the lowest mercury levels (≤0.40 μg/L), women with mercury >1.81 μg/L (upper quintile) showed 2.24 (95% CI=1.22, 4.12) greater odds for thyroglobulin autoantibody positivity (p(trend)=0.032); this relationship was not evident for thyroid peroxidase autoantibody positivity. Results suggest an association between mercury and thyroglobulin autoantibody positivity.
Vitamin D insufficiency, defined as serum levels of 25-hydroxyvitamin D [25(OH)D3] lower than 30 ng/mL, has been reported to be prevalent in several autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. The goal of the present study was to assess whether vitamin D insufficiency is also a feature of Hashimoto's thyroiditis (HT).
We performed a prevalence case-control study that included 161 cases with HT and 162 healthy controls. Serum levels of 25(OH)D3, calcium, phosphorus, and parathyroid hormone were measured in all 323 subjects.
The prevalence of vitamin D insufficiency in HT cases (148 of 161, 92%) was significantly higher than that observed in healthy controls (102 of 162, 63%, p < 0.0001). Among HT cases, the prevalence rate of vitamin D insufficiency showed a trend to be higher in patients with overt hypothyroidism (47 of 50, 94%) or subclinical hypothyroidism (44 of 45, 98%) than in those with euthyroidism (57 of 66, 86%), but the differences were not significant (p = 0.083).
Vitamin D insufficiency is associated with HT. Further studies are needed to determine whether vitamin D insufficiency is a casual factor in the pathogenesis of HT or rather a consequence of the disease.
Antibodies to thyroglobulin (Tg), thyroperoxidase (TPO), and TSH receptor (TSH-R) are prevalent in autoimmune thyroid diseases. We aimed to assess whether females with Graves disease or Hashimoto thyroiditis are more likely than age-matched controls to have thyroid antibodies before clinical diagnosis and to measure the timing of antibody seroconversion.
This was a nested case-control study using the Department of Defense Serum Repository and the Defense Medical Surveillance System, 1998-2007. We assessed thyroid antibodies in the serum of 522 female, active-duty, military personnel including: 87 Graves disease cases, 87 Hashimoto thyroiditis cases, and 348 age matched controls. One serum sample was available at the time of the clinical diagnosis (±6 months); three additional samples were retrieved from the repository up to 7 yr before the clinical diagnosis, for a total of 2088 samples.
In Hashimoto thyroiditis, TPO antibodies were found in about 66% of the cases at all time points. Tg antibodies showed a similar stationary trend, at a lower prevalence of about 53%at all time points. No TSH-R antibodies were found. In Graves disease, TPO antibodies gradually increased from 31% at 5-7 yr prior to diagnosis to 57% at diagnosis and Tg antibodies from 18 to 47%. TSH-R antibodies were present before diagnosis and showed an increasing prevalence from 2, 7, 20, to 55%.
Antibodies to Tg, TPO, and TSH-R precede by years the development of the diagnostic autoimmune thyroid diseases phenotype. Overall, the presence of thyroid antibodies in apparently healthy individuals should not be neglected.
To the Editor: An 88-year-old Chinese woman was brought to the emergency department by her family, who reported that she had been lethargic and unable to walk or swallow for 3 days. She had been eating an estimated 1.0 to 1.5 kg of raw bok choy daily for several months in the belief that it would help control her diabetes. She had no previous history of thyroid disease. On examination the patient was lethargic. The temperature was 36.1°C, the pulse 58 beats per minute, blood pressure 181/89 mm Hg, and the respiratory rate 22 breaths per minute. A pulse oximetry . . .
The association between autoimmune thyroiditis (AIT) and thyroid cancer is still not clear despite many previous reports. This study investigated whether serologic thyroid antibodies are predictive of thyroid cancer in patients with thyroid nodules.
We retrospectively reviewed records of patients with thyroid nodules evaluated by ultrasonography-guided fine-needle aspiration cytology at our institution between January 2006 and December 2008. Thyroid autoimmunity was assessed by measuring thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb). The final outcome deciding a benign or malignant status involved a combination of cytology and histology.
Of the 1638 patients, malignant nodules had a higher rate of positive TgAb (30.8% vs. 19.6%; p < 0.001) and elevated thyrotropin (TSH) levels (2.5 +/- 2.8 mIU/L vs. 2.1 +/- 2.0 mIU/L; p = 0.021) than benign nodules. The rate of positive TPOAb was not higher in malignant nodules, although both TPOAb and TgAb were well correlated with TSH levels and histological AIT. In the multivariate analysis, a positive TgAb was significantly associated with thyroid cancer (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.12-2.33) with upper tertile of normal range of TSH levels (OR = 1.72, 95% CI 1.12-2.63) and above normal range of TSH levels (OR = 1.98, 95% CI 1.06-3.70).
We report for the first time that a positive serum TgAb test was an independent predictor for thyroid malignancy in thyroid nodules along with serum TSH levels regardless of the presence of AIT. Our results suggest that TgAb measurement could give additional information for predicting malignancy in cytologically indeterminate thyroid nodules in conjunction with clinical risk factors and TSH levels.
To assess the roles of dietary protein (Pr) and calcium (Ca) level associated with excessive fluoride (F) intake and the impact of dietary Pr, Ca, and F on thyroid function, 144 30-day-old Wistar albino rats were randomly allotted to six groups of 24 (female:male = 1:1). The six groups were fed (1) a normal control (NC) diet (17.92% Pr, 0.85% Ca = NC group); (2) the NC diet and high F (338 mg NaF [=150 mg F ion]/L in their drinking water = NC+F group); (3) low Pr and low Ca diet (10.01% Pr, 0.24% Ca = LPrLCa group); (4) low Pr and low Ca diet plus high F = LPrLCa+F group; (5) high Pr and low Ca diet plus high F (25.52% Pr, 0.25% Ca = HPrLCa+F group); and (6) low Pr and high Ca diet plus high F (10.60% Pr, 1.93% Ca = LPrHCa+F group). The areas of thyroid follicles were determined by Image-Proplus 5.1, and triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) levels in serum were measured by radioimmunoassay. The histopathological study revealed obviously flatted follicular epithelia cells and hyperplastic nodules, consisting of thyroid parafollicular cells that appeared by excessive F ingestion, on the 120th day. Pr or Ca supplementation reverses the F-induced damage in malnutrition. The serum T3, FT3, T4, and FT4 levels in the NC+F group were significantly decreased and significantly increased in the LPrLCa+F group. Thus, excessive F administration induces thyroid dysfunction in rats; dietary Pr and Ca level play key roles in F-induced thyroid dysfunction.
Recently published biochemical data suggest the significant role of selenium compounds as the adjuvants combined with L: -thyroxine therapy, which can reduce antithyroid peroxidase antibodies' (TPOAb) levels in patients with Hashimoto disease. The study was undertaken to document in a more detailed way the changes in parameters expressing the thyroid and ovarian function brought about by selenium supplementation (50-100 microg/day) in a woman undergoing autoimmune thyroiditis (AIT) therapy. This prospective observational case study lasted for 14 months plus additional 5 months as a follow-up period. Parameters reflecting selenium status, thyroid metabolism, and sex hormones secretion were determined at the onset and end of the study period, as well as in some of its middle points. During the supplementation trial, serum selenium (Se) increased by 45% and plasma glutathione peroxidase (GPX3) by 21%. TPOAb decreased by 76%. All other parameters also fluctuated during the supplementation period, but all results were always within normal physiological ranges. After withdrawal of the supplementation, the sharp fall of Se and GPX3 promptly occurred, and this phenomenon was accompanied with a marked increase in TPOAb. This report stresses the importance of selenium supplementation in AIT treatment. However, the efficiency and durability of the effect of Se supplementation on the TPOAb titer remain an open question. The clarification of mechanism(s) underlying Se interaction with autoimmune processes should throw new light on this issue.
To undertake a systematic review of literature published between 1980 and 2008 on the incidence of autoimmune thyroid disease.
All relevant papers found through searches of Medline, EMBASE and ScienceDirect were critically appraised and an assessment was made of the reliability of the reported incidence data.
The reported incidence of autoimmune hypothyroidism varied between 2.2/100 000/year (males) and 498.4/100 000/year (females) and for autoimmune hyperthyroidism, incidence ranged from 0.70/100 000/year (Black males) to 99/100 000/year (Caucasian females). Higher incidence rates were found in women compared to men for all types of autoimmune thyroid disease. The majority of studies included in the review investigated Caucasian populations mainly from Scandinavia, Spain, the UK and the USA. It is possible that nonautoimmune cases were included in the incidence rates reported here, which would give an overestimation in the incidence rates of autoimmune disease presented.
To our knowledge this is the most comprehensive systematic review of autoimmune thyroid disease conducted in the past two decades. Studies of incidence of autoimmune thyroid disease have only been conducted in a small number of mainly western countries. Our best estimates of the incidence of hypothyroidism is 350/100 000/year in women and 80/100 000/year in men; the incidence of hyperthyroidism is 80/100 000/year in women and 8/100 000/year in men.
Unlabelled:
The effects of total fasting for 31 +/- 10 days followed by re-alimentation with an 800 calorie diet on thyroid function, i.e. T4,T3,rT3,RT3U (resin T3 uptake), and TSH, and on TBG levels in serum were studied sequentially in obese hospitalized patients (N=18). Additionally, cortisol, growth hormone, prolactin, parathyrin and free fatty acids were followed as hormonal and metabolic parameters, respectively. Further, CBG, transferrin, alpha 2-haptoglobin and complement C'3 were measured as representatives of other serum proteins. Results before fasting: T4, T3, TBG, cortisol, CBG, alpha 2-haptoglobin and complement C'3 of the obese patients were elevated when compared with healthy normal weight controls, whereas rT3, T4/TBG ratio, T3/TBG ratio, TSH, coritsol/cbg ratio, growth hormone, prolactin, parathyrin and transferrin of the obese group were normal. RT3U and fT4 index were decreased in the obese patients. Results during fasting: Significant decreases were observed during fasting for the following parameters -- T3, TBG, T3/TBG ratio, transferrin, alpha 2-haptoglobin complement C'3. rT3, T4/TBG ratio, RT3U, fT4 index and FFA increased. T4, tsh response to TRH stimulation, cortisol, CBG, cortisol/cbg ratio, parathyrin, growth hormone and prolactin did not change. Results during re-alimentation: T3, TBG, T3/TBG ratio, TSH response to TRH, transferrin, alpha 2-haptoglobin and complement C'3 increased. Conversely, fT3, RT3U, FFA, cortisol and cortisol/cbg ratio decreased whereas the other parameters did not change.
Conclusions:
1) There is no evidence for primary hypothyroidism in obese patients during prolonged fasting and re-alimentation. 2) The rapid decrease of T3 and increase of RT3U after initiation of fasting are not fully explained by the observed slower decreases in TBG. 3) The alterations of T3, rT3 and RT3U resemble in their kinetics the changes in FFA levels. 4) Fasting reduced the levels of only certain serum proteins, interestingly TBG, transferrin, alpha 2-haptoglobin and complement C'3, all of which, except transferrin, are elevated in obesity. 5) The magnitude of the observed decreases does not suggest any clinically relevant deficiencies in serum proteins. 6) Re-alimentation reverses rapidly all observed changes.
The deiodinative pathways T4 and the production of T3 and rT3 were compared in two groups of normal volunteers on physiological T4 replacement. One group was given a normal diet and the second group was fasted up to 15 days. After 1 week of fasting, the mean serum T3 level fell from 140 to 93 ng/dl, and the mean serum rT3 level rose from 51 to 106 ng/dl. No significant change occurred in the group mean serum concentration of TSH or total or free T4. These changes were most marked during the fifth to seventh day of fasting, but recovered partly toward the baseline values during the second week of fasting. The ratio of mean serum T3 to mean serum rT3 was 2.8 before fasting. It diminished to 0.9 after 1 week of fasting and increased to 1.5 after 2 weeks of fasting. In seven control subjects, the MCRs of T4, T3, and rT3 were 1.27 ± 0.24, 24.0 ± 3.6, and 105 ± 13 liters/day. 70 kg, respectively (mean ± sd). The disposal rates of T4, T3, and rT3 were 140 ± 16, 41 ± 5, and 49 ± 12 μg/day.70 kg, respectively. In seven fasting subjects, the MCRs of T4, T3, and rT3 were 0.95 ± 0.17 (P<0.01) 19.3 ± 3.9 (P<0.05), and 55 ± 15 liters/day.70 kg (P<0.001), whereas the disposal rates of T4, T3, and rT3 were 113 ± 14 (P<0.005), 17 ± 4 (P<0.001), and 58 ± 9 μ/day.70 kg (P<0.2), respectively. The clearance of rT3 was reduced 52%, and the T3 disposal rate was reduced to 41% in the fasting subjects. The mean rT3 disposal rate remained unchanged, but the rT3 disposal to T4 disposal ratio rose from 0.35 to 0.51 during fasting. The T4 to T3 conversion rate was reduced to 50% and the T4 to rT3 conversion rate was increased to 146% in the fasting group as compared to the control group. The proportion of T4 metabolized by deiodination remained unchanged (77% in the control group and 76% in the fasting group). The results suggest that in subjects of good health, severe caloric deprivation impaired iodothyronine deiodiation in general, and in particular the deiodination at 5' position, thereby reducing both T3 production and rT3 clearance. Significant shunting of T4 metabolism away from T3 production into rT3 production was noted. Fasting did not alter the proportion of T4 undergoing metabolism via the deiodinative pathways compared to the nondeiodinative pathways.
Ten days of total energy deprivation evoked the following endocrine changes in 12 healthy, normal-weight males: early and marked reductions and increments in the blood levels of T3 and reverse T3, respectively, with rapid returns to pre-starvation levels after refeeding; a slight and late decrease in the blood levels of T4; a minute reduction of the blood levels of TSH; a pronounced increase in the blood levels of growth hormone, but a return towards pre-exposure levels even before discontinuation of starving; a minor and gradual enhancement of the blood levels of cortisol, and an increase in nocturnal urinary adrenaline excretion. It is assumed that these changes reflect a complex regulatory mechanism, the purpose of which is to secure adequate energy supply to vital organs.
This study examined the influence of aerobic fitness on the responses of selected hormones to the combined stressors of sleep deprivation (SD) and sustained mental work. Six aerobically high fit (HF) (VO2max greater than 50 ml.kg-1.min-1) and six average fit (AF) (VO2max less than 40 ml.kg-1.min-1) female subjects were subjected to a period of sleep loss of 60 h during which time they performed sustained mental tasks with no physical activity component. Venous blood samples were drawn every 12 h at 1330 hours and 0130 hours and plasmas analyzed for cortisol, growth hormone (hGH), prolactin, thyroxine (T4), triiodothyronine (T3), and reverse-triiodothyronine (rT3). For cortisol, both the HF and AF groups exhibited the normal high-daytime and low-nighttime pattern of secretion, with levels increasing significantly as the duration of SD increased. The normal elevations of hGH and prolactin levels during normal sleep were suppressed during SD. No significant fitness effects were found for cortisol, hGH, and prolactin responses. Plasma levels of T4, T3, and rT3 increased significantly during SD, with highly fit subjects exhibiting higher levels of these hormones than those of average fitness. We suggest that aerobic fitness may influence the peripheral metabolism of T4 during SD, but that aerobic fitness does not influence the regulation of the classical stress hormones during SD.
To determine the hormonal response to acute spinal cord injury, serial serum samples were collected from 18 patients with acute spinal cord injury and from 14 control patients with spinal fractures without cord injury. The first sample was taken within 24 hours of injury, the second at 24-48 hours; and the third at 7 days for determination of thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), T3 uptake (T3U), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG), growth hormone (GH), cortisol, and insulin. Significant increases were observed in rT3 levels and transient changes were observed in the T4 and T3 levels in the spinal cord injured group but not in the group with spinal fractures alone. The changes in the spinal cord injured patients are consistent with the 'low T3 syndrome'. However, the persisting rise of rT3 at 7 days was an unexpected finding. In addition to the cord injury, these changes may also be related to dexamthasone administration and nutritional factors.
The toxic effects of cadmium on the thyroid gland of pregnant rats were studied with an electron microscope and an X-ray microanalyzer. Serum levels of thyroid hormones (T3 and T4) were also analyzed. Deterioration of the rough-surfaced endoplasmic reticulum occurred in the thyroid follicular epithelium on the fifth day of cadmium treatment. Large intracellular vacuoles, which arose from dilated cisternae of the rough-surfaced endoplasmic reticulum, were fused together, and marked swelling of the mitochondria was also noted. Thyroglobulin-secreting granules at the apical cytoplasm were decreased in number. By energy dispersive X-ray microanalysis, cadmium peaks were preferentially obtained from swollen mitochondria in the follicular epithelial cells. Serum levels of T3 and T4 were significantly decreased in cadmium-treated rats dams when compared to those of controls. In the present experiment, cycloheximide also caused degenerative changes in the rough-surfaced endoplasmic reticulum and the disappearance of thyroglobulin-secreting granules. Cycloheximide is a known inhibitor of protein synthesis on cytosolic ribosomes. These results indicated that accumulated cadmium in the mitochondria of thyroid follicular epithelial cells might disturb the oxidative phosphorylation of this organelle and the loss of energy supply possibly caused the inhibition of the synthesis and release of thyroid hormones.
1. An insufficient dietary supply of iodine results in the development of a variety of disorders of thyroid function and development of the fetus and young infants, grouped under the general heading of Iodine Deficiency Disorders, IDD. Endemic goiter constitutes the most spectacular disorder from the clinical and epidemiological point of view. However, the most serious consequence of iodine deficiency is the impact on neuro-intellectual development at a population level, varying from endemic mental retardation to the complete picture of endemic cretinism. 2. Considering that mental retardation due to iodine deficiency represents the longterm consequence of hypothyroidism occurring during the perinatal period, it is presently recognized that the target groups to the effects of iodine deficiency at a population level are, by order of priority, the fetus, the newborn, the pregnant woman, the child and, finally, the adult. 3. The newborn is more susceptible than the adult to the effects of iodine deficiency. Consequently, systematic screening for congenital hypothyroidism in endemic areas is a particularly sensitive index for detecting the presence and action of goitrogens in the environment and for monitoring the effects of programs of iodine prophylaxis. 4. IDD are particularly prevalent in developing countries. However, large areas or even countries in Europe are still obviously iodine deficient. For example, the iodine intake in adults in Belgium is 50 to 70 micrograms/day which is lower than the recommended dietary allowance for iodine (at least 100 micrograms/day). 5. IDD should be corrected on a world scale, including in Europe. Special attention should be devoted to the protection of mother and child. Within this framework, the iodine content of formula milk should be increased in Europe. 6. Finally, correction of iodine deficiency in Europe would decrease the avidity of the thyroid for iodide and, consequently, would constitute the most efficient preventive measure in case of nuclear fallout.
Thyroid peroxidase (TPO), the major enzyme in the thyroid hormone synthesis, multifunctionally catalyzes (1) iodide oxidation, (2) iodination of the precursor protein, and (3) a coupling reaction of iodotyrosyl residues. The present study was carried out to examine the mercurial effects on the iodination, the second step of TPO. Purified porcine thyroglobulin or bovine serum albumin as acceptor protein was iodinated with [125I]NaI and H2O2 by purified porcine TPO. Iodinated protein was separated by acid precipitation on membrane filter or paper chromatography. Both CH3HgCl and HgCl2 dose-dependently inhibited the iodination, but HgCl2 was more potent to inhibit the iodination than CH3HgCl. These mercurial effects on the second step resemble the effects on the third step which were already reported; but are in marked contrast to the effects on the first step, where TPO was inhibited by HgCl2 but never by CH3HgCl.
Repeated low-dose injections of mercuric chloride (HgCl2) in the brown Norway (BN) rat result in polyclonal activation which includes the induction of anti-glomerular basement membrane (GBM) autoantibodies. We examined the kinetics of various autoantibodies produced in vivo, general features of polyclonal activation such as total IgG levels and immune complex formation, and the relationship between organ specific autoimmunity and tissue injury in the kidney and thyroid. The production of immune complexes and autoantibodies to GBM and thyroglobulin was short lived, and the increase in levels of total IgG and antibodies to ssDNA and dsDNA was prolonged; the antibody response to collagen types I and II was intermediate in duration. Autoantibodies induced by HgCl2 caused only mild and variable tissue injury in the kidneys and did not induce abnormalities in the thyroid. These studies demonstrate that immunostimulation by mercury may result in the formation of a range of autoantibodies, with variable kinetics and pathogenicity.
In a recent work, we provided evidence that the in vitro inhibitory effect of cyclosporin A (CsA) was potentiated by the addition of another immunosuppressive molecule, the 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the present study, we investigated the in vivo influence of the association of both drugs administered at infratherapeutic doses, using an experimental model of autoimmune thyroiditis in CBA mice. Treatment regimen of the animals was initiated at priming with thyroglobulin (Tg) and consisted of daily administration of CsA (10 and 20 mg/kg/day, intragastrically) and/or 1,25(OH)2D3 (0.1 and 0.2 microgram/kg/day, ip) for 21 days. Control mice that were given a placebo preparation orally and the vehicle of vitamin D3 metabolite ip developed a severe disease as assessed by histological examination on Day 28 postimmunization and detection of circulating anti-Tg antibodies. Treatment with either drug administered alone at the doses mentioned above did not affect the incidence of thyroiditis and only reduced by up to 26% the severity of histological lesions. In contrast, the mice treated simultaneously with both drugs exhibited a lower incidence of thyroid pathology and developed a significantly milder disease (P less than 0.001) as compared to controls. However, there was no alteration in the levels of anti-Tg antibodies. This in vivo beneficial effect of low doses of CsA and 1,25(OH)2D3 was not due to an accumulation of CsA in the blood of treated mice since the levels of CsA were similar, regardless of the administration of 1,25(OH)2D3. Our data suggest that these two immunomodulatory agents used together at low doses may be an effective therapy of autoimmune disorders with fewer side effects.
In addition to direct toxic effects on endocrine organs chronic alcohol intake affects regulation of endocrine systems by disturbed liver function. As a result in patients with alcohol-induced liver cirrhosis gonadal axis is characterized by low total and free testosterone, elevated estradiol. LH, FSH, and sexual hormone binding globulin and an enhanced conversion of testosterone to estradiol. Prolactin also is found to be elevated. The thyrotropic axis is characterised by low T3- und T4- as well as elevated rT3-values and normal TSH. STH is elevated, while somatomedin C is decreased. The corticotropic axis may show an abolished circadian rhythm, a negative Dexamethasone-test, low transcortin and elevated free cortisol levels. The disturbance of the calcitropic axis leads to osteoporosis and osteomalacia, due to intestinal hyperparathyroidism and vitamin D malnutrition. In 50% of chronic alcoholics there are elevated insulin and glucagon values and a pathological glucose tolerance test.
(Z)-Guggulsterone, a ketosteroid isolated from the oleoresin of the dry exudate of Commiphora mukul, has been shown to stimulate the thyroid function in rats. This drug is now shown to counteract the thyroid-suppressant activity of a known thyroid inhibitor (carbimazole). This set of observations distinguishes the thyroid stimulatory action of (Z)-guggulsterone from that of the thyroid stimulatory hormone (TSH) of pituitary origin. It is, therefore, concluded that the action of (Z)-guggulsterone is not mediated by the pituitary.
Groups of male rats weighing about 350 g were inserted polyethylene tubings into bile duct and femoral vein under pentobarbital anesthesia. Several iodothyronines (i.e. T4, T3, rT3, 3,5-T2, 3,3'-T2 and 3',5'-T2) were estimated in 2-hr portions of bile with the aid of specific radioimmunoassay. After the infusion of ethanol (0.3 ml/hr/rat for 4 hr) an increase of biliary excretion of rT3 and a decrease of 3,5-T2 was found as compared to controls. When 5 mg linoleic acid was added to 1.2 ml ethanol, the increase of rT3 was significantly higher than that after ethanol only and, in addition, significant increase of 3',5'-T2 excretion was found. It was concluded that both ethanol and unsaturated fatty acids may inhibit 5'-monodeiodination in the liver and that unsaturated nonesterified fatty acids may exert such effect even when administered intravenously without underlying metabolic disorders.
The effect of cadmium on thyroxine (T4) outer ring monodeiodination was studied in vivo and in vitro in the rat liver. One microgram of T4 was incubated with rat liver homogenates in 50 mM Tris--HCl buffer, pH 7.4, with or without 0.5, 5, and 50 mM dithiothreitol (DTT) for 60 min in the presence of 10(-8) to 10(-3) M CdCl2, and the amount of 3,5,3'-triiodothyronine (T3) produced was determined by a specific radioimmunoassay. Subcutaneous injection of CdCl2, 1 mg/kg BW/day, 5 days a week for 10 weeks, to the rats resulted in a significant reduction in serum T3 concentration (by 37%) and hepatic T3 production from T4 (by 78 to 92%). In vitro addition of 1 microM to 1 mM CdCl2 to liver homogenates caused a concentration-dependent reduction in T3 generation. Without DTT a 50% reduction in the T4 to T3 converting activity was caused by 4 X 10(-6) M CdCl2. DTT (0.5 to 50 mM) partially restored T3 generation roughly in a concentration-dependent manner. These results indicate that cadmium has some effects on the metabolism of thyroid hormone.
Plasma levels of TSH and thyroid hormones in 22 male and 27 female medical students were determined by radioimmunoassay before and after an academic examination. The plasma values of TSH were slightly higher in both sexes on the examination day than on the control days. The values were lower after the examination than before it in females but not in males. Plasma levels of T3 were higher in males than in females on the examination day. In contrast, the plasma rT3 values were higher for females on the examination day than on control days. The plasma levels of T4 were similar in both sexes. The results suggest that during psychic stress, the pituitary-thyroid endocrine system of the female reacts differently from that of the male.
The impact of varying caloric intake on peripheral monodeiodination and plasma disposal of T3, rT3, and the three diiodothyronines (T2) was studied in five normal subjects while they were consuming a low calorie diet (1200 Cal/day) and again while receiving a high calorie diet (3600 Cal/day). Toward the end of each diet period 240 nmol 3,3'-T2 (126 micrograms) and 80 nmol 3',5'-T2 (42 micrograms) were infused for 7 h, and a bolus injection of 137 nmol 3,5-T2 (72 micrograms) was followed by a 12-h infusion of 69 nmol 3,5-T2 (36 micrograms) and 111 nmol rT3 (72 micrograms) on another day. [125I]T3 (30 muCi) was injected on the third day. The T2 and rT3 concentrations were measured by RIA during the 2 days of infusion, and the serum disappearance of [125I]T3 was studied by immunoprecipitation and trichloroacetic acid precipitation of the labeled T3. Four to 5% of the plasma disposal of T3 was accounted for by 3'-monodeiodination, and 36-39% by 5-monodeiodination. Increasing caloric intake resulted in a higher overall plasma disposal rate of T3, but no change in the percentage of T3 metabolized by monodeiodination pathways. In contrast, 5'-monodeiodination accounted for 21% of the total plasma disposal of rT3 during the low calorie diet and 45% during the high calorie intake. This increase in 5'-monodeiodination of rT3 was at the expense of alternative pathways of disposal. A marked increase in the plasma clearance rate of 3,5-T2 was also found during the high calorie diet, indicating that the level of caloric intake affects pathways of metabolism other than outer ring monodeiodination. These studies emphasize the important role played by diet in the regulation of peripheral thyroid hormone metabolism through modulating outer ring monodeiodination, and that overnutrition changes other pathways of iodothyronine metabolism as well.
The development of autoimmune thyroid disease (AITD) is dependent on abnormal function of the immune system. Although this immune regulatory malfunction is usually secondary to a genetic predisposition, a number of environmental factors can influence the expression of AITD and also affect its course. Graves' disease and Hashimoto's thyroiditis are common AITDs, and the study of these two disorders has greatly expanded our knowledge of autoimmune disease in general. Recent data have suggested that endemic goiter and sporadic nontoxic goiter also may be autoimmune disorders. In this article we discuss current information regarding environmental factors that may play a role in the pathogenesis and progression of these autoimmune thyroid diseases. Exposure to excess iodine, certain drugs (amiodarone, lithium), infectious agents, and pollutants, and stress have all been implicated.
In a previous study from this laboratory, chlorine dioxide (ClO2) treated drinking water depressed thyroxine (T4) levels in the African green monkey. The present study again demonstrated a decrease in T4 levels in the same species after 4 wk of oral exposure. However, after 8 wk of treatment T4 levels rebounded to above pretreatment levels, coinciding with an increase in thyroid radioiodide uptake. This T4 rebound phenomenon and increased iodide uptake may be due to a compensatory endocrinological mechanism. In rats, T4 levels dropped during the 8-wk ClO2 treatment period in a dose-dependent manner, and no rebound effect was observed. Iodide uptake values in the rat were not affected. It appears that ClO2 may have an effect on thyroid function in both species.
This review surveys the occurrence, analysis, and properties of glucosinolates and derived compounds in plants and products intended for humans and animal consumption. The paper, which includes references published in 1981, is also intended to compliment existing reviews on the chemistry of these sulfur‐containing natural products. Particular emphasis is placed upon members of the Brassica family because of their importance as vegetables, condiments, oilseeds, and animal feedingstuffs. Since much of the work considered here relates to glucosinolate decomposition products, biochemical information concerning the nature, occurrence, and properties of the glucosinolate‐degrading enzyme, myrosinase, is considered in Section III. The methods available for the chemical analysis of glucosinolates and their various breakdown products are discussed critically. Factors affecting the glucosinolate content of plants and plant products arc outlined in Section VII. Particular emphasis is placed upon the effect of processing on the concentration and nature of breakdown products and on the myrosinase activity. The role of glucosinolate breakdown products on flavor development is examined in Section VIII. The more general effects, both beneficial and adverse, of these compounds in food are discussed in Section X. Since such effects in animal feedingstuffs have been the subject of regular reviews, these are considered here only briefly. Contraindications in the literature are pointed out, areas which have been inadequately explored are highlighted, and suggestions are made for future research.
Acute effects of methylmercuric chloride and mercuric chloride on thyroidal functions were examined. The organic mercurial concentration of 4 x 10(-5) M inhibited by 50% of Na+K+ATPase in the membraneous preparation from the hog thyroid, and 6 x 10(-7) M of the inorganic mercurial showed the same extent of the inhibition. The Mg2+ ATPase activity in the preparation was neither affected by CH3HgCl up to a concentration of 2 x 10(-3) M, nor by HgCl2 up to 1 x 10(-4) M. After an intraperitoneal injection to mice of 5 micrograms of mercurial per gram body weight daily for 2 consecutive days, the 4-hour and the 24-hour uptakes of 131I by the thyroids were partially reduced by both organic and inorganic mercurials. A significant reduction in percentages of labeled iodothyronines was demonstrated to suggest that mercurial may cause a coupling defect in the synthesis of iodothyronines. Incubation of hog thyroglobulin with 8 x 10(-3) M of methylmercuric chloride caused no observable aberration in slab disc electrophoreogram, but the protein was apparently denatured by the same concentration of mercuric chloride suggesting that thyroglobulin may carry a large binding capacity against either mercurial, but the inorganic mercurial can be more potent denaturant of the protein. The in vitro lysosomal hydrolysis of the mercurial-pretreated rat thyroglobulin which was labeled with 125I in vivo and fortified with the carrier hog thyroglobulin was not affected, but the direct addition of either mercurial in the medium resulted in a significant inhibition of the proteolytic action. Iodotyrosine deiodinase in the thyroid was inhibited by both mercurials in in vitro and in vivo systems. A partial reduction in the serum bound 131I-iodide in both mercurial treated groups was observed at 4 hours and 24 hours after the radioiodide administration. The blood thyroxine levels estimated by radioimmunoassay were quite reduced in the inorganic mercurial treated group and also moderately reduced in the methylmercurial treated group, indicating that the hormone secretion was affected by mercurials.
Nutrition influences thyroid function at the level of TSH secretion, at the level of monodeiodination, and possibly elsewhere. In order to study the effect of starvation on TSH secretion, 8 healthy male volunteers fasted for 30 h and were then refed with 800 kcal. Refeeding was performed at 19.00 h and blood was sampled at 20 min intervals until midnight. Control experiments were performed in the same subjects both when they were normally fed and when the starvation period was prolonged a further 5 h until midnight. Starvation decreased serum TSH levels to below 1 mU/l, and without refeeding the nocturnal peak of the TSH nycthemeral rhythm was abolished. With refeeding serum TSH tended to increase towards midnight and was significantly higher than during starvation. However, the serum TSH levels remained significantly below those at the same time of the day in the absence of a preceding starvation period.
Serum T 3 levels were significantly lower than in the fed state. The mean values were 1.84 ± 0.03 vs 2.30 ± 0.06 nmol/l (120 ±2 vs 150 ± 4 ng/100 ml, mean ± sem P < 0.01). Refeeding did not result in a measurable change in serum T 3 concentration (1.80 ± 0.05 nmol/l; 120 ± 3 ng/100 ml, mean ± sem , n.s.). The contrary was true for rT 3 levels which increased in starvation and tended to fall with refeeding, but this decrease was not significant.
As glucocorticoids have been implicated in the control of monodeiodination and TSH secretion, serum cortisol levels were also measured. They did not differ during the 3 experimental periods. The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion.
The results show that short-term starvation and refeeding may be a valuable tool for studying in vivo control of TSH secretion.
Starvation is accomplished by significant changes in the hypothalamic-pituitary-thyroid axis and in peripheral thyroid hormone metabolism. Less well studied, however, are the effects on thyroid hormone economy produced by hypocaloric feeding. We explored these changes in obese patients fed 200, 400, or 600 cal/day of either carbohydrate of protein for 28 days. T4' T3' reverse T3 and the TSH response to TRH were measured at frequent intervals. Each patient demonstrated a transient rise in reverse T3 and a fall in T2 that returned to near basal levels by the end of the study period. The TSH response to TRH on the other hand, declined to approximately 50% of control values and remained at that level throughout the course of study, regardless of the type of substrate or calorie level chosen. The results indicated that hypocaloric feeding is associated with changes in thyroid hormone economy similar to those in starvation and that peripheral (changes in T3 and rT3) and central (TRH response) events are controlled by separate mechanisms.
The inner ring monodeiodination [T4 to rT3, T3 to 3,3'-diiodothyronine(3,3'-T2)] as well as the outer ring monodeiodination (T4 to T3, rT3 to 3,3'-T2) was demonstrated with thyroid tissues obtained from patients with Graves' disease by measuring the products by RIAs. Sequential deiodination of T4 to 3,3'-T2 was also recognized in normal human thyroid glands. These iodothyronine deiodinations were dependent on incubation time, tissue volume, temperature, pH, and concentration of dithiothreitol. The monodeiodination of rT3 to 3,3'-T2 proceeded very rapidly and the maximal production of 3,3'-T2 was obtained at about 5 min. In the other reactions, the products accumulated in an almost linear fashion during the period of 60 min. The optimal pH for 5-monodeiodination was 9.0, while that for 5-monodeiodination was 5.5-6.5. In the absence of dithiothreitol, all of these reactions were abolished. Propylthiouracil and iopanoic acid inhibited the reactions, whereas methimazole and potassium iodide had no effect. Kinetic study revealed that the apparent Km and maximum velocity of the conversion of T3 to 3,3'-T2 were 10.9 microM and 19 pmol 3,3'-T2/mg protein.min, respectively, and that those of rT3 to 3,3'-T2 were 0.37 microM and 80 pmol 3,3'-T2/mg protein.min, respectively. There was a significant difference in the conversion of T4 to rT3 between normal [0.56 +/- 0.04 pmol/mg protein.min (mean +/- SE)] and Graves' thyroids 0.88 +/- 0.06 pmol/mg protein min). Moreover, a significant difference was found between 3,3'-T2 production rate from T3 or rT3 in the Graves' thyroids and that in the normal thyroids. The overall reaction from T4 to 3,3'-T2 in the Graves' thyroids (4.04 +/- 0.70 pmol/mg protein.min) was significantly higher than that in the normal thyroids (0.63 +/- 0.11 pmol/mg protein.min; P less than 0.001). The results indicate the existence of 5-deiodinase that produces rT3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from T3, and 5'-deiodinase that produces T3 from T4 and 3,3'-T2 from rT3 in human thyroids. Accelerated conversion of T4 to 3,3'-T2 via either T3 or rT3 was observed in Graves' thyroid glands.
To investigate the relationship between energy availability (dietary energy intake minus energy expended during exercise) and thyroid metabolism, we studied 27 untrained, regularly menstruating women who performed approximately 30 kcal.kg lean body mass (LBM)-1.day-1 of supervised ergometer exercise at 70% of aerobic capacity for 4 days in the early follicular phase. A clinical dietary product was used to set energy availability in four groups (10.8, 19.0, 25.0, 40.4 kcal.kg LBM-1.day-1). For 9 days beginning 3 days before treatments, blood was sampled once daily at 8 A.M. Initially, thyroxine (T4) and free T4 (fT4), 3,5,3'-triiodothyronine (T3) and free T3 (fT3), and reverse T3 (rT3) were in the normal range for all subjects. Repeated-measures one-way analysis of variance followed by one-sided, two-sample post hoc Fischer's least significant difference tests of changes by treatment day 4 revealed that reductions in T3 (16%, P < 0.00001) and fT3 (9%, P < 0.01) occurred abruptly between 19.0 and 25.0 kcal.kg LBM-1.day-1 and that increases in fT4 (11%, P < 0.05) and rT3 (22%, P < 0.01) occurred abruptly between 10.8 and 19.0 kcal.kg LBM-1.day-1. Changes in T4 could not be distinguished. If energy deficiency suppresses reproductive as well as thyroid function, athletic amenorrhea might be prevented or reversed by increasing energy availability through dietary reform to 25 kcal.kg LBM-1.day-1, without moderating the exercise regimen.
In order to evaluate the time course of changes in serum concentration of thyroid hormones, cortisol and ACTH in patients exposed to chemical weapons containing sulfur mustard, we measured serum concentrations of hormones on the first, third and fifth week following injury in 13 soldiers and compared them to the results obtained from 34 control men. Free T4 and T3 indices were decreased and rT3, cortisol and ACTH were increased in the first week following exposure. There was a subnormal TSH response to TRH in 2 of 3 men tested. Except for an increase in FT4I and a decrease in TSH by the third week, and a steady decline in serum cortisol, serum hormone concentrations were unchanged until the fifth week after injury. The decline in serum cortisol occurred despite a constant increase in serum ACTH. By the fifth week only 1 of 13 men had serum cortisol levels >10μg/dl.
We conclude that exposure to chemical weapons containing sulfur mustard results in alterations in serum concentrations of thyroid and adrenal hormones and ACTH, resembling changes seen in burn trauma. Some evidence of direct effects of mustard on endocrine glands exist.
To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone.
Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared.
The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02).
An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.