[RECENT ACQUISITIONS ON THE RELATIONS BETWEEN PERNICIOUS ANEMIA AND THYROID DISEASES].
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Anemia↗
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Environmental iodine intake affects the type of nonmalignant thyroid disease.
The relationship between the iodine intake level of a population and the occurrence of thyroid diseases is U-shaped with an increase in risk from both low and high iodine intakes. Developmental brain disorders and endemic goiter caused by severe iodine deficiency may seriously deteriorate overall health status and economic performance of a population. Severe iodine deficiency with a median 24-hour urinary iodine excretion of the population below 25 microg needs immediate attention and correction. Less severe iodine deficiency with median urinary iodine excretion below 120 microg per 24 hours is associated with multinodular autonomous growth and function of the thyroid gland leading to goiter and hyperthyroidism in middle aged and elderly subjects. The lower the iodine intake, the earlier and more prominent are the abnormalities. At the other end of the spectrum, severely excessive iodine intake starting at median urinary iodine excretion levels around 800 microg per 24 hours is associated with a higher prevalence of thyroid hypofunction and goiter in children. A number of studies indicate that moderate and mild iodine excess (median urinary iodine >220 microg per 24 hours) are associated with a more frequent occurrence of hypothyroidism, especially in elderly subjects. The exact mechanism leading to this has not been clarified, and more studies are needed to define the limits of excessive iodine intake precisely. Due to the frequent occurrence of thyroid disorders, proper monitoring and control of the population iodine intake level is a cost-effective alternative to diagnosing, therapy and control of the many individual cases of thyroid diseases that might have been prevented.
Aging↗
Prevalence of nonthyroid specific autoantibodies in autoimmune thyroid diseases.
To clarify the involvement of polyclonal activation of autoimmune reaction in organ-specific autoimmune diseases, we investigated the prevalence of nonthyroid specific autoantibodies in 50 patients with autoimmune thyroid diseases (22 patients with Graves' disease and 28 with Hashimoto's disease) and in 50 age- and sex-matched controls. None of the 100 subjects had any clinical manifestations or laboratory data indicating any other immunological, infectious, hepatic, or malignant diseases. The prevalence of positive antibodies to nucleus, smooth muscle, and single-stranded DNA in the patients (26%, 36%, and 34%, respectively) was higher than that in the control group (8%, 4%, and 4%, respectively), although neither group was positive for autoantibodies against double-stranded DNA, extractable nuclear antigen, SS-A, SS-B, mitochondria, or rheumatoid factor. Furthermore, 66% of the patients had at least one autoantibody to nucleus, smooth muscle, or single-stranded DNA. In conclusion, patients with autoimmune thyroid diseases show high prevalence of autoantibody against not only thyroid-specific, but also nonthyroid-specific antigens. These results are consistent with the concept that immune reaction of patients with organ-specific autoimmune diseases may be polyclonally accelerated to the production of antibodies against both organ and nonorgan specific autoantigens.
Adult↗
ACOG practice bulletin. Thyroid disease in pregnancy. Number 37, August 2002. American College of Obstetrics and Gynecology.
Because thyroid disease is the second most common endocrine disease affecting women of reproductive age, obstetricians often care for patients who have been previously diagnosed with alterations in thyroid gland function. In addition, both hyperthyroidism and hypothyroidism may initially manifest during pregnancy. Obstetric conditions, such as gestational trophoblastic disease or hyperemesis gravidarum, may themselves affect thyroid gland function. This document will review the thyroid-related pathophysiologic changes created by pregnancy and the maternal-fetal impact of thyroid disease.
Female↗
[A simple health control for the elderly. Screening for vitamin B12 deficiency and thyroid disease].
Screening for vitamin B12 deficiency and thyroid disease is cheap and enables early diagnosis to be made and treatment to be started while it is still simple and can prevent the development of such serious conditions as dementia, depression, or irreversible tissue damage. In 1995-6, 83% (126/151) of all 75-year-olds in Härryda, a district (population 28,500) to the east of Gothenburg, agreed to undergo a health control designed to detect hypo- or hyper-thyroidism or vitamin B12 deficiency among elderly residents without symptoms (or with atypical symptoms not easily recognised). Of the 126 participants, four (3%) had low plasma cobalamin (vitamin B12) levels (a figure similar to or lower than those reported by others), and were treated with vitamin B12 after further examination; eight (6%) had serum thyroid stimulating hormone (TSH) levels below the lower normal limit, though further examination showed all eight to be euthyroid; and two (1.6%) were diagnosed as being hypothyroid (a lower prevalence than figures reported elsewhere), and were treated with laevothyroxine. The findings suggest that such screening might be useful in primary care. However, the clinical diagnosis of vitamin B12 deficiency, and of hypo- or hyperthyroidism, is often difficult, especially in the elderly; and although a low serum TSH level is also considered to be a reliable marker of hyperthyroidism, like others this study showed that it may occur even in the absence of disease. Thus, serum TSH and plasma B12 levels are useful screening variables, but need to be complemented by other tests before diagnosis is set.
Aged↗
[Circulating HLA-DR (Ia) positive T cells and T cell activation by thyroglobulin, thyroid microsome and TSH-receptor in autoimmune thyroid diseases].
HLA-DR antigens are not expressed on normal circulating T lymphocytes, but recently it has become apparent that HLA-DR antigens are expressed on immunologically activated T lymphocytes, as well as monocytes, macrophages, and B lymphocytes. Namely, the HLA-DR antigens are considered to be one of the activated T cell antigens. It is apparent from the previous studies that increased numbers of HLA-DR positive T cells frequently appear in the circulation in systemic autoimmune diseases, such as RA and SLE. Furthermore, in such diseases, it is reported that the variations in circulating HLA-DR positive T cells are related to the activity of the diseases. In this communication, we examined the variations in HLA-DR positive T cells in the peripheral blood of the patients with autoimmune thyroid diseases. HLA-DR positive T cells were detected by cytotoxicity test using anti HLA-DR mouse monoclonal antibody (Leu-HLA-DR antibody) and rabbit complement. The results indicate that; 1) The percentage of HLA-DR positive T cells were increased in the patients with autoimmune thyroid diseases. 2) The changes of HLA-DR positive T cells accompanied with the stimulation by non-specific mitogens in vitro in autoimmune thyroid diseases did not differ from those in the normal controls. 3) The percentage of HLA-DR positive T cells increased by the stimulation of TSH-receptor and thyroid microsome in Graves' disease, on the other hand, it occurred by the stimulation of thyroglobulin and thyroid microsome in Hashimoto's thyroiditis. 4) The percentage of HLA-DR positive T cells were correlated with TRAb (TSH receptor Ab assayed by Smith's kit) in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Thyroid disease in relation to pregnancy: a decade of change.
Inspection of the references cited in this review indicates that much work has occurred in the area of thyroid and pregnancy during the last decade. Significant advances in our understanding of the immunology of pregnancy and the effect of thyroid disease on this process have taken place. The role of hCG in the physiology of pregnancy and its relevance to thyroid function has been an emerging theme. There is still no clear explanation for the association between thyroid antibodies and infertility or miscarriage. During the last decade a general concensus has developed in relation to the management of hyperthyroidism in pregnancy although there are still variations in antithyroid drug use at this time. The aetiological classification of congenital hyper- and hypothyroidism utilizing new technologies has opened up a new perspective on these disorders. Attention has been drawn to the importance of treating maternal hypothyroidism with adequate thyroid replacement therapy and to the possibility of impaired child neuropsychological development consequent on low maternal thyroid hormone concentration in early gestation in non iodine deficient areas. Significant advances have been made during the last decade in the description of the clinical features and in our understanding of the pathogenesis of postpartum thyroid disease. The importance of long-term follow up of selected patient groups has also been emphasized.
Abortion, Spontaneous↗
Chronic autoimmune thyroid disease in children and adolescents in the years 1999-2004 in Lower Silesia, Poland.
The aim of the study was to analyze data related to chronic autoimmune thyroid disease at diagnosis and at follow-up of children and adolescents in Lower Silesia in the years 1999-2004. Age, gender, incidence of thyroid disease in the family, clinical presentation, hormonal findings, levels of thyroid antibodies, results of ultrasonography, and fine needle aspiration biopsy (FNAB) were recorded. 100 children, 10 boys and 90 girls, were included in the analysis. The mean age at diagnosis was 12.3+/-2.3 years and at last examination 14.9+/-1.9 years. At diagnosis, increased levels of TSH without overt hypothyroidism was observed in 26 children. In 11 children hyperthyroidism was detected whereas 63 children were euthyroid. An increased level of thyroid peroxidase antibodies was observed in 65% of the children. Ultrasonography was characteristic for Hashimoto's thyroiditis in all patients. Fine needle biopsy was performed when there were diagnostic difficulties (35% children). Thus, in all the children the diagnosis of Hashimoto's thyroiditis was ascertained either by high antibody titer or FNAB. Associated diseases were observed in 33% of the children. Thyroid disease in the family was present in 25% of the children. There was a gradual decline in the number of new cases presented from 1999 to 2004. The reason for this decline remains speculative.
Adolescent↗
Repeated fine-needle aspiration of the thyroid in benign nodular thyroid disease: critical evaluation of long-term follow-up.
UNLABELLED: Fine-needle aspiration (FNA) is the most effective diagnostic means in the management of nodular thyroid disease. Therefore, we decided to evaluate the diagnostic reproducibility of FNA and the usefulness of repeated FNA in benign nodular thyroid disease. We evaluated 799 satisfactory aspirations performed in 306 patients (298 females) aged 14-84 years, followed for 2-12 years. FNAs were performed on an annual basis. Of all patients, 299 (97.71%) maintained benignity: 230 (75.16%) repeated the same cytologic pattern, and 69 (22.54%) showed diagnostic variations within benign pathologies. In 3 patients (0.98%) the diagnosis changed to suspicious and in 4 (1.30%) to papillary carcinoma in the whole group. Of these 4 cases, 1 was diagnosed in the second (0.57%) and 3 in the third repeat FNA (2.25%). In 6 cases in which increased nodular size was observed, no change to malignancy was detected, while 3 of the carcinomas found showed no changes in size. IN CONCLUSION: (1) The variation in cytologic diagnoses within benign pathologies can be attributed to the coexistence of nonuniform pathologies. Aspirations performed in different sites of the nodule would contribute to obtain a more representative specimen. (2) In the absence of suspicious clinical changes and with at least three FNAs confirming the cytologic diagnosis of benignity, the follow-up of nodules by FNA could be discontinued and (3) In our experience, the diagnostic change from benign to malignant after three repeat FNAs appears to indicate that it would be advisable to perform three procedures.
Adolescent↗
[Immunological aspects of auto-immune thyroid diseases (author's transl)].
Sufficient evidence exists to relate auto-immune thyroid diseases (including both Graves-Basedow's disease and Hashimoto's thyroiditis) to primary disturbances of the lymphatic system. Currently available data underline the importance of immunological factors, either humoral or tissular, in the physiopathological expression of these diseases, their basic genetic disorder appearing to be a specific lack of "suppressor" T lymphocytes. This results in the survival and multiplication of an unwanted clone, appearing by chance, of "helper" T lymphocytes directed specifically towards the thyroid. These lymphocytes then cooperate with groups of previously existing appropriate B lymphocytes, which then produce immunoglobulins directed against the thyroid. Subtle genetic differences determine the appearance of either Graves-Basedow's disease or Hashimoto's thyroiditis with their typical clinical manifestations. In fact, these subtle genetic differences between the different groups of patients with Graves-Basedow's disease may result in the total absence of immunity control (thus preventing any immunological remission) whereas partial lack may occur with the possibility of remission. The role of stress in the development of hyperthyroidism may be related to the effects of an aggression on a T lymphocyte population already partially deficient.
Autoantibodies↗
Incorrect diagnosis of thyroid disease by junior doctors.
Thyroid function tests (TFTs) are commonly performed on elderly patients admitted to hospital. Several diseases and commonly used drugs may alter thyroid function test results. We assessed the knowledge of such interactions among 50 junior doctors in our departments: 60% were unaware that (in our laboratory) the normal range for TFTs is the same in those above 65 years as in those below; 72% correctly noted the effect of an acute illness, while only 48% correctly noted the effect of a chronic illness on test results; 72% were well aware of common drug effects such as those of the oral contraceptive pill, but only 22% and 42% knew of the potentially more important interactions in the elderly with the salicylates and phenytoin respectively. Thyroid screening in elderly people is important. The knowledge of interactions between drugs, disease states and the normal range of biochemical assays used in routine thyroid screening needs to be improved if thyroid function tests are to be interpreted appropriately.
Clinical Competence↗
Expression of Pax-8, p53 and bcl-2 in human benign and malignant thyroid diseases.
BACKGROUND: Immunohistochemical expression of the transcription factor Pax-8 in human thyroid diseases has never been investigated. The relationship between Pax-8, bcl-2 and p53 in thyroid neoplasms is also matter of interest. MATERIALS AND METHODS: Seventy-three thyroid tissue samples were evaluated for the expression of Pax-8, p53 and bcl-2 using the immunoperoxidase technique. The series included 11 follicular adenomas, 11 goitres, 23 papillary carcinomas, 16 follicular carcinomas, 6 undifferentiated carcinomas and 6 medullary carcinomas. RESULTS: The percentage of Pax-8 positive cells ranged from 14.9 to 27.1% and 10.1 to 39% in goitres and follicular adenomas, respectively. Among differentiated carcinomas, follicular histotype showed a Pax-8 immunoreactivity ranging from 0 to 26.5% of the neoplastic cells whereas in papillary carcinomas the percentage of positive cells ranged from 0 to 16.8%. None out of the six undifferentiated carcinomas showed Pax-8 immunoreactivity. The same negative pattern was noticed in medullary carcinomas. A statistically significant difference in Pax-8 expression was observed between non-malignant and malignant diseases (p < 0.0001). A different reactivity for Pax-8 was also noticed between differentiated carcinomas and undifferentiated carcinomas (p = 0.07). None of the benign tissues stained for p53 whereas among malignant specimens different percentages of p53 expression were observed with all undifferentiated carcinomas expressing the highest positivity (range 24.1-88.6%). Finally, when a combined analysis of bcl-2 and Pax-8 reactivity was carried out, some carcinomas proved to be Pax-8 negative and bcl-2 positive whereas others showed a similar immunoreactive pattern for both Pax-8 and bcl-2. CONCLUSIONS: Pax-8 is mainly expressed in benign rather than in malignant thyroid diseases and, among neoplasms, differentiated carcinomas express Pax-8 more frequently than undifferentiated carcinomas. An inverse pattern was observed for p53. Bcl-2 seems to be partially related to Pax-8 expression. However, a Pax-8 independent bcl-2 expression is also evident.
Adenocarcinoma, Follicular↗
Interaction of highly purified thyroid peroxidase with anti-microsomal antibodies in autoimmune thyroid diseases.
Among the several antigens involved in autoimmune thyroid diseases, the microsomal antigen has been recently identified as the human thyroid peroxidase (TPO). The availability of highly purified TPO and anti-TPO monoclonal antibody (mAb) allowed us to study in more details anti-TPO autoimmune antibodies (aAb) and their relationship with anti-microsomal aAb. Only sera with anti-microsomal aAb, as assayed by passive hemagglutination, highly immunoprecipitated purified TPO; anti-thyroglobulin aAb did not contribute to this effect. IgG binding to TPO and inhibition of mAb binding to TPO were also observed using anti-microsomal positive and anti-thyroglobulin negative sera. The correlation between anti-TPO and anti-microsomal aAb titers was found significant (p less than 0.02). These data suggest that anti-microsomal and anti-TPO immunoreactivity are presented by the same aAb. It could not be ruled out, however, that some of the anti-microsomal aAb detected by passive hemagglutination could be directed against antigens different from TPO. The use of highly purified TPO and anti-TPO mAb would allow large scale studies of anti-TPO aAb, necessary for investigating their pathological significance in thyroid disorders.
Antibodies, Monoclonal↗
Changes in plasma fibronectin levels in thyroid diseases.
The plasma levels of fibronectin (Fn) have been measured in normal subjects and in patients with thyroid diseases. The mean plasma Fn levels in 62 normal adults was 32.0 +/- 6.0 mg/dl, whereas it was elevated to 62.6 +/- 16.1 mg/dl (mean +/- SD) in 25 patients with hyperthyroidism and decreased to 19.2 +/- 8.0 mg/dl in 9 patients with hypothyroidism. The 9 patients with simple goiter have normal values of 29.1 +/- 8.0 mg/dl. With the administration of anti-thyroid drugs, plasma Fn levels normalized, with a time lag, in parallel with normalization of the thyroid function. Positive correlation was obtained between Fn levels and serum levels of triiodothyronine (T3) and thyroxine (T4). The present findings indicate that measurement of plasma Fn both in the basal state and during treatment provides evidence of altered Fn metabolism in thyroid diseases and serves to follow up the effect of treatment.
Adolescent↗
[Changes in plasma fibronectin levels in patients with thyroid disease and its mechanism].
Plasma fibronectin (FN) level was determined in normal subjects and patients with thyroid disease by the Laurell method. In vitro effect of triiodothyronine (T3) on FN synthesis by cultured human fetal skin fibroblasts was also studied. Plasma FN level was 32.2 +/- 5.5 mg/dl (mean +/- SD) in normal adults, and no sex difference was observed. The plasma FN concentrations were increased in patients with hyperthyroidism (63.3 +/- 15.2 mg/dl), decreased in patients with hypothyroidism (19.5 +/- 6.5 mg/dl), and in normal range in patients with simple goiter (30.2 +/- 7.0 mg/dl). These FN values have been normalized with a time lag of a short period after their thyroid function became normal. There was a positive correlation between plasma FN concentrations and serum T3 or T4 concentrations, but a inverse correlation between plasma FN concentrations and serum thyroxine binding globulin or cholesterol levels. In vitro studies revealed that the addition of T3 to the incubation medium stimulated FN synthesis by human fetal skin fibroblasts at the concentrations between 10(-8)M and 10(-6)M. These results indicate the usefulness of plasma FN determination in patients with thyroid disease for their management and studying pathophysiology of the disease, and suggest at the fluctuation of plasma FN concentrations in these patients may at least in part due to the effect of thyroid hormone on FN synthesis by the cells.
Adolescent↗
[DNA typing of HLA antigen in patients with autoimmune thyroid disease using the PCR-SSOP method].
The purpose of this study was to investigate HLA-linked genetic factors involved in the pathogenesis of autoimmune thyroid disease such as Graves' disease and Hashimoto's thyroiditis. In 76 Graves' disease patients and 317 healthy Japanese controls, HLA-A, -B, -C, DR and DQ specificities were determined by serologic typing and HLA-DPB1 alleles were typed by DNA typing using the PCR-SSOP method. The frequencies of HLA-A2, B46 and DPB1*0501 were increased in Graves' patients. The highest odds ratio (10.5) was observed in individuals possessing both DPB1*0501 and HLA-A2. This observation suggests a synergic involvement of HLA class II allele (DPB1*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Graves' disease. Genotypes of DQA1 and DQB1 genes were determined by the PCR-SSOP method in 105 patients with goitrous Hashimoto's thyroiditis to investigate whether specific DQ alleles were associated with susceptibility or resistance to autoimmune thyroid disease. Hashimoto's thyroiditis was found to be negatively associated with DQA1*0102 and DQB1*0602. No strong positive association with a specific DQ allele was found in Hashimoto's thyroiditis. These results suggest that the HLA-DQ gene may be a genetic marker for resistance to Hashimoto's thyroiditis.
Alleles↗
Sensitization of T lymphocytes to thyroglobulin and thyroperoxidase in autoimmune thyroid diseases.
To investigate T-cell sensitization to thyroid autoantigens in autoimmune thyroid disease (AITD), purified soluble human thyroglobulin (Tg) and thyroid peroxidase (TPO) were used. Peripheral blood mononuclear cells (PBMC) as well as CD8-depleted, CD4-enriched PBMC ("selected" PBMC) from 9 patients with Graves' disease (GD), 13 Hashimoto's thyroiditis (HT) and 10 healthy subjects, were cultured for 6 days with or without varying concentrations (0.1, 1.0 and 5.0 micrograms/ml, respectively) of Tg or TPO and their responses were evaluated using the 3H-thymidine incorporation assay. Total PBMC as well as selected PBMC from GD and HT responded to both TPO and Tg, but normal PBMC did not. This induction was more marked in "selected" PBMC; on the other hand, CD8 depletion did not permit normal PBMC to respond to either antigen. However, reactivity of selected AITD PBMC to Tg differed from that of TPO. Two way analysis of variance showed that the proliferative response was significantly greater with Tg than with TPO, (again particularly notable with the "selected" PBMC) in both GD and HT. There was no difference between control and AITD preparations when an irrelevant (renal microsomal) antigen was employed. Taken together with our previous report that CD4 cells were induced by TPO even when cultured with CD8 cells, it is evident that suppressor CD8 cells do play a role in CD4 cells from proliferating against Tg and TPO; however their function alone or in combination with suppressor-inducer CD4 cells is partially disturbed, so that T cell sensitization to Tg and TPO can be identified in the AITD PBMC.
Adult↗
Increased risk of autoimmune thyroid disease in hepatitis C vs hepatitis B before, during, and after discontinuing interferon therapy.
BACKGROUND: Thyroid gland dysfunction has been reported to occur with variable frequency during interferon alfa (IFN-alpha) therapy in patients with the hepatitis C virus (HCV). We prospectively evaluated if the prevalence of autoimmune thyroid disease in patients with HCV differs from that in patients with the hepatitis B virus (HBV) before, at the end of, and 6 months after stopping treatment with IFN-alpha. METHODS: One hundred thirty-four patients with HCV and 41 patients with HBV were studied. Measurements of serum free thyroxine, free triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), and thyrotropin-binding inhibitory immunoglobulin were performed. RESULTS: Positive levels of TPOAb and TgAb were found in 20% and 11% of patients with HCV compared with 5% and 3% of patients with HBV, respectively. At the end of IFN-alpha therapy, thyroid gland dysfunction was more prevalent in patients with HCV (12%) compared with those with HBV (3%), with thyrotropin levels significantly higher in the HCV group (P = .03). Titers of TPOAb, TgAb, and thyrotropin-binding inhibitory immunoglobulin increased significantly (P = .02, P = .04, and P = .02, respectively) at the end of IFN-alpha therapy in patients with HCV but not in those with HBV. Patients who developed thyroid gland dysfunction were predominantly female (P = .03), had decreased levels of free triiodothyronine (P<.001), and had a higher prevalence of TPOAb (P = .03) before treatment with IFN-alpha. Thyroid gland dysfunction was reversed in 60% of those with HCV 6 months after discontinuing treatment with IFN-alpha. CONCLUSIONS: Patients with HCV are more susceptible than patients with HBV to autoimmune thyroid disease. Systematic screening of thyroid gland function and TPOAb titers in all patients with HCV before, during, and after IFN-alpha therapy appears warranted. This precaution is not necessary for patients with HBV.
Adolescent↗