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PubMedDate not supplied

Autoimmune thyroid disease and pregnancy: relevance for the child.

As a group, the autoimmune thyroid diseases, including Graves' disease, Hashimoto's thyroiditis, and primary myxedema, are among the most common endocrine disorders encountered during pregnancy. Therefore, a substantial number of offspring will grow and develop in utero under conditions of maternal autoimmune thyroid disease and may be exposed to abnormal maternal thyroid function, maternal thyroid antibodies, and/or numerous therapeutic agents used to manage maternal thyroid dysfunction. This article reviews the effects that these various aspects of maternal autoimmune thyroid disorders can have on pregnancy outcome, as well as on the physical growth, neuropsychological development, and thyroid status of the developing fetus and neonate.

Antithyroid Agents↗

PubMed2001

Prevalence of thyroid diseases in Nevada counties with respect to perchlorate in drinking water.

Perchlorate is well-known to inhibit the uptake of iodine by the thyroid and has been shown to do so at doses in the milligrams-per-day range and higher. Perchlorate has been found in the water supply of Clark County (Las Vegas), Nevada, at 4 to 24 micrograms/L (parts per billion) and may provide exposure dosages in the tens of micrograms per day. An analysis of the Medicaid database from Nevada was undertaken to determine whether an increase in the prevalence of any thyroid disease was associated with that level of perchlorate content. The prevalence of persons being seen for thyroid disease or for specific thyroid diseases (goiter, nodule, thyrotoxicosis, congenital hypothyroidism, acquired hypothyroidism, thyroiditis, and other thyroid disorders) and for thyroid cancer among the Medicaid-eligible population of each county was calculated for the 2-year period 1997 to 1998. The prevalences in Clark County were compared with those in Washoe County (i.e., Reno), the second most populous county in the state, and with those for the rest of the state. There was no evidence of an increased rate of thyroid disease (or of any specific thyroid disease) associated with perchlorate exposure. Generally, the prevalences in the metropolitan parts of the state were lower than for the rest of the state, particularly for acquired hypothyroidism. This analysis found no evidence that perchlorate-containing drinking water at the given level increased the prevalence of acquired hypothyroidism or of any other thyroid condition.

Humans↗

PubMed1987

Familial dysalbuminemic hyperthyroxinemia associated with primary thyroid disease.

This study describes a family with intrinsic thyroid disease in addition to familial dysalbuminemic hyperthyroxinemia, a syndrome associated with euthyroidism and increased binding of thyroxine to serum albumin. The simultaneous occurrence of thyroid disease and elevated serum thyroxine concentrations due to familial dysalbuminemic hyperthyroxinemia may confound the diagnosis of the two concurrent disorders and the subsequent therapy of the thyroid disease.

Adult↗

PubMed1990

Geographical distribution of subclinical autoimmune thyroid disease in Britain: a study using highly sensitive direct assays for autoantibodies to thyroglobulin and thyroid peroxidase.

In order to determine whether the geographical distribution of autoimmune thyroid disease in Britain is influenced by the pattern of iodine intake, the prevalence of subclinical disease (detectable antithyroid antibodies in biochemically euthyroid individuals) has been measured in female blood donors from seven towns in England and Wales previously characterised in terms of past and present iodine intake. Thyroglobulin antibody and thyroid peroxidase antibody were measured by highly sensitive assays which are based on the direct interaction between antibody and radiolabelled antigen. Excluding cases of overt thyroid disease (biochemically hypo- or hyperthyroid with thyroid antibodies), the overall prevalences of the antibodies in sera from the 698 female blood donors were 17.8% for thyroglobulin antibody and 17.8% for thyroid peroxidase antibody. Both antibodies were found in 12.3% of the female blood donors. In contrast, the prevalences of thyroglobulin antibody and thyroid peroxidase antibody were 41 and 43%, respectively, in the 117 female relatives of 18 probands with autoimmune thyroid disease, but the highest prevalences were observed in groups of women patients with Graves' disease (N = 39) or Hashimoto's disease (N = 39) (51, and 97% for thyroglobulin antibody, respectively, and 72 and 97% for thyroid peroxidase antibody, respectively). Antibody prevalence increased with age in the female blood donors rising from 10.6% at age 18-24 to 30.3% at age 55-64 for thyroglobulin antibody and from 14.9% at age 18-24 to 24.2% at age 55-64 for thyroid peroxidase antibody. Geographical differences in the prevalences of both antibodies were not significant and did not correlate with either the previous goitre prevalence or with current differences in iodine intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

Occurrence of thyrocyte HLA class II expression in a wide variety of thyroid diseases: relationship with lymphocytic infiltration and thyroid autoantibodies.

The proteins of the major histocompatibility system (HLA in humans) play an essential role in the regulation of immune responses due to their involvement in the presentation of antigen to T lymphocytes. Thyroid follicular cells (thyrocytes) from patients with Graves' disease and Hashimoto's thyroiditis demonstrate increased expression of HLA class I and aberrantly or inappropriately express class II antigens, a phenomenon that may play an important role in the pathogenesis of these autoimmune diseases. To establish if these changes in the expression of HLA molecules are characteristic of thyroid autoimmune disease, the immunopathological features (including class I and class II antigen expression) of 100 thyroidectomy specimens from patients with nonautoimmune thyroid disease were studied by indirect immunofluorescence, and the results compared with the findings in specimens from 14 patients with Graves' disease and 12 subjects undergoing laryngectomies for carcinoma. Increased class I product expression was found in 61% of all tissues studied, with maximal occurrence in papillary carcinomas (100%) and Graves' disease (86%), but it was also detected in 50% of the glands containing nodular lesions and in 16% of the control glands. Inappropriate class II molecule expression was found in Graves' disease (71%), hyperplastic nodules (53%), multinodular glands (44%), papillary carcinomas (38%), and 16% of the control glands. In summary, an increase in inappropriate HLA class I and class II expression was very common in nonautoimmune thyroid glands, but it generally occurred in the context of lymphocytic infiltration and thyroid autoantibodies (i.e. focal thyroiditis). Multiple correlation analyses of these 4 phenomena indicated heterogeneity in the mechanism leading to the inappropriate expression of thyrocyte class II antigens in the different conditions studied.

Adolescent↗

PubMed1988

Neonatal thyroid disease: differential expression in three successive offspring.

Neonatal thyroid disease, manifested as either hyperthyroidism or hypothyroidism, has been described in the offspring of women with autoimmune thyroid disorders. We report clinical and laboratory observations in a mother with autoimmune thyroiditis who gave birth to three children with different forms of thyroid dysfunction. The first child was clinically normal, the second child had transient neonatal hyperthyroidism, and the third child had neonatal hypothyroidism. After the birth of the second child, the mother was found to be biochemically hypothyroid. Long-acting thyroid stimulator and antithyroid microsomal antibodies were detected in her serum. She was treated with L-T4 (0.15 mg/day). After the birth of her third child, the mother was found to have thyroid-stimulating immunoglobulins and TSH-blocking inhibitory immunoglobulins in her serum. The latter also were detected in the third newborn. Six weeks later, TSH-blocking inhibitory immunoglobulins were not detected in the child, but they persisted in the mother. This report further expands the spectrum of neonatal thyroid disease and suggests that differing disease syndromes in the newborn can occur depending on whether stimulating or blocking antibodies predominate in the mother.

Adult↗

PubMedDate not supplied

Thyroid disease: a guide for the head and neck surgeon.

Head and neck surgeons are involved in the diagnosis and therapy of thyroid disease with increasing frequency. The surgical techniques utilized for the management of thyroid disease are well known by most head and neck surgeons and will not be discussed in this paper. It is the head and neck surgeons' knowledge of the physiology, medical disorders, and the proper evaluation of the patient with thyroid disease that is most open to criticism. This paper reviews thyroid physiology, basic tests used to assess thyroid function in health and disease, thyroiditis, thyroid carcinomas, and nodules of the thyroid gland. The signs, symptoms, laboratory findings, and the methods of medical and surgical therapy are discussed for each of these disorders. The supplement is not intended to provide expertise, but will provide a general and basic knowledge of thyroid disease.

Adenocarcinoma↗

PubMed2002

Detection of thyroid peroxidase mRNA in peripheral blood of patients with malignant and benign thyroid diseases.

The aim of this study was to evaluate thyroid peroxidase (TPO) mRNA expression in peripheral blood of patients with benign and malignant thyroid disease. Included were 120 thyroid cancer patients, 85 patients with goitre or Graves' disease (GD) and 54 healthy volunteers. TPO mRNA expression was analysed in peripheral blood by nested RT-PCR. In cancer patients, RT-PCR results were compared with staging, grading and serum thyroglobulin (TG) measurement. TPO transcripts were detected in 7/10 (70%) patients with known metastases of thyroid cancer and in 39 of 110 (36%) patients without metastases (P<0.05), in 15/44 (34%) patients with goitre, in 17/41 (41%) cases with GD and in 4/54 (7.4%) subjects in the control group (P<0.05, controls vs all patients with thyroid disease). Among cancer patients without metastatic disease, RT-PCR results correlated positively with lymph node status (P=0.05), grading (P=0.01) and elevated serum thyroglobulin levels (P=0.03). This is the largest study investigating the use of the TPO-RT-PCR assay. Positivity in TPO-RT-PCR correlates significantly with metastatic disease in cancer patients and with the presence of thyroid disease in general. To date, TPO-RT-PCR cannot substitute for standard techniques in the diagnosis of local recurrence or metastatic spread in thyroid cancer patients. However, as results of TPO-RT-PCR correlate significantly with lymph node status, grading and serum TG measurements in patients with non-metastatic disease, TPO seems to be an interesting molecular marker to look at in follow-up studies.

Adult↗

PubMed2002

Autoimmune thyroid disease in systemic lupus erythematosus.

BACKGROUND: The reported prevalence of autoimmune thyroid disease (3.9-24%) and antithyroid antibodies (11-51%) in SLE varies considerably. Early reports were mainly based on short term studies of small cohorts. OBJECTIVE: To report the prevalence of autoimmune thyroid disease and thyroid antibodies in 300 patients with SLE, followed up at our centre between 1978 and 2000, by a retrospective analysis of case notes. RESULTS: The prevalence (5.7%) of hypothyroidism in our cohort was higher than in the normal population (1%), while that of hyperthyroidism (1.7%) was not significantly different. Overall 42/300 (14%) of our cohort had thyroid antibodies, rising to 15/22 (68%) in the subgroup who also had thyroid disease (p<0.001). Both antimicrosomal and antithyroglobulin antibodies were detected. The antibodies were found in equally high frequency in the hyperthyroid subgroup (80% patients), whereas in the hypothyroid subgroup antimicrosomal antibodies were more frequent than antithyroglobulin antibodies (64% v 41%). There was no significant difference in the frequency with which antimicrosomal or antithyroglobulin antibodies were detected between the hyperthyroid and hypothyroid subgroups (p>0.2). CONCLUSION: Our patients with SLE had a prevalence of hypothyroidism, but not hyperthyroidism, greater than that of the normal population. The presence of either condition was associated with a higher frequency of both antimicrosomal and antithyroglobulin antibodies.

Adult↗

PubMed1995

Prevalence of incidental thyroid disease in a relatively low iodine intake area.

An ultrasonographic survey of thyroid abnormalities was conducted in 547 consecutive apparently normal overweight subjects (380 females and 167 males), aged 27-58 years in an urban area with relatively low iodine intake (mean daily urinary iodine excretion: 10.6 micrograms/dL). Individuals with any previous thyroid disease or familial thyroid pathology were excluded. In 240 subjects (44%) high resolution ultrasonography of the thyroid was considered normal. In 307 individuals (56%) abnormalities of the echo structure (39%) or thyroid nodular disease (17%) were detected by ultrasonography. Marked heterogeneity of the echo structure that was considered suggestive of chronic autoimmune thyroiditis was present in 81 subjects (15%). In 72 of these patients the serum anti-TPO levels were positive by a sensitive RIA. Thyroid nodules either solid or predominantly cystic were present in 90 subjects (17%). Eighteen patients had a relatively large nodule (diameter 15-18 mm). Eleven of these nodules were missed at clinical examination. Fine needle aspiration cytology was performed in 14 patients and 7 individuals underwent thyroid surgery. In 6 subjects the pathologic diagnosis was benign adenomatous goiter and one patient had a follicular carcinoma. Thyroid function studies confirmed subclinical hypothyroidism in 27 patients (4.9%), all of them with elevated serum anti-TPO autoantibodies levels. It was concluded that the overall occurrence of thyroid disease is more common than suspected by clinical examination.

Adolescent↗

PubMed1988

[Autoimmune thyroid diseases and Gougerot-Sjögren syndrome].

Thyroid autoantibodies have been found in 28 to 38 per cent of Sjögren's syndrome cases. In this study, we inversely investigated, the presence of Sjögren's syndrome antibodies in autoimmune thyroid diseases, ie rheumatoid factors, antinuclear soluble antigens SSB/La and SSA/RO, anti-salivary ducts. Results show no increased incidence of these antibodies in autoimmune thyroid diseases as compared to those of control subjects. So, no significant immune abnormality association is found between these two autoimmune disorders.

Adult↗

PubMed2004

Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

CONTEXT: Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. OBJECTIVES: To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. DATA SOURCES: MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. STUDY SELECTION AND DATA EXTRACTION: A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. DATA SYNTHESIS: The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. CONCLUSIONS: Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.

Humans↗

PubMed2003

PDS is a new susceptibility gene to autoimmune thyroid diseases: association and linkage study.

Autoimmune thyroid disease (AITD), including Graves' disease (GD), Hashimoto thyroiditis (HT), and primary idiopathic myxedema, is caused by multiple genetic and environmental factors. Genes involved in immune response and/or thyroid physiology appear to influence susceptibility to disease. The PDS gene (7q31), responsible for Pendred syndrome (congenital sensorineural hearing loss and goiter), encodes a transmembrane protein known as pendrin. Pendrin is an apical porter of iodide in the thyroid. To evaluate the contribution of PDS gene in the genetic susceptibility of AITD, we examined four microsatellite markers in the gene region. Two hundred thirty-three unrelated patients (GD,141; HT, 54; primary idiopathic myxedema, 38), 15 multiplex AITD families (104 individuals/46 patients) and 154 normal controls were genotyped. Analysis of case-control data showed a significant association of D7S496 and D7S2459 with GD (P = 10(-3)) and HT (P = 1.07 10(-24)), respectively. The family-based association test showed significant association and linkage between AITDs and alleles 121 bp of D7S496 and 173 bp of D7S501. Results obtained by transmission disequilibrium test are in good agreement with those obtained by the family-based association test. Indeed, evidence for linkage and association of allele 121 bp of D7S496 with AITD was confirmed (P = 0.0114). Multipoint nonparametric linkage analysis using MERLIN showed intriguing evidence for linkage with marker D7S496 in families with only GD patients [Z = 2.12, LOD = 0.81, P = 0.026]. Single-point and multipoint parametric LOD score linkage analysis was also performed. Again, the highest multipoint parametric LOD score was found for marker D7S496 (LOD = 1.23; P = 0.0086) in families segregating for GD under a dominant model. This work suggests that the PDS gene should be considered a new susceptibility gene to AITDs with varying contributions in each pathology.

Alleles↗

PubMed2000

Population screening for autoimmune thyroid disease.

Whether or not healthy adults in the community would benefit from screening for autoimmune thyroid disease is controversial. Although the prevalence of unsuspected overt thyroid disease is low, a significant proportion of subjects tested will have evidence of mild thyroid failure or excess. This article assesses whether subclinical thyroid disease is of sufficient clinical importance to warrant screening and, once detected and confirmed, to justify therapy. Population screening for autoimmune thyroid disease is assessed against recently revised screening criteria, using data from epidemiologic studies. Recommendations are proposed that may be applied in any iodine-replete community.

Adolescent↗

PubMed1993

Autoantibodies in the sera of patients with autoimmune thyroid disease recognize a secreted form of human thyroid peroxidase generated in a baculovirus system.

We used a baculovirus vector to express the cDNA for a truncated (amino acid residues 1-848), secreted form of thyroid peroxidase (TPO) in Sf9 insect cells. Immunoreactive TPO was detected in pooled conditioned media from 10 clones using polyclonal TPO autoantibodies in the sera of patients with autoimmune thyroid disease. As a further test of TPO immunogenicity, the pooled media completely inhibited autoantibody binding to antigen. We used an ELISA to compare autoantibody reactivity to insect cell-derived TPO and TPO antigen produced by Chinese hamster ovary (CHO) cells, the standard form of antigen in present use. In a study of 22 TPO antibody-negative sera and 24 sera with different TPO autoantibody potencies, there was a highly significant correlation (r = 0.977; p < 0.001) in OD values obtained with TPO from the two different sources. The highest producing baculovirus clone generated 8.5 micrograms TPO/ml of conditioned medium, nearly 10-fold higher than previously achieved with stably transfected Chinese hamster ovary cells. Baculovirus-derived, soluble TPO therefore is an excellent source of recombinant TPO in further studies to examine the precise B cell epitopes for human autoantibodies.

Animals↗

PubMed1997

The epidemiology of thyroid disease and implications for screening.

The burden of thyroid disease in the general population is enormous. As many as 50% of people in the community have microscopic nodules, 3.5% have occult papillary carcinoma, 15% have palpable goiters, 10% demonstrate an abnormal thyroid-stimulating hormone level, and 5% of women have overt hypothyroidism or hyperthyroidism. Despite this high prevalence of thyroid disease, screening for these disorders is not recommended by any major health agency. This article explores the epidemiologic issues surrounding this complex problem by analyzing prevalence, incidence, and mortality data from a worldwide variety of sources.

Adult↗

PubMed1993

Thyroid hormones and autoantibodies in pregnant patients with thyroid diseases.

Serum concentrations of thyroid stimulating hormone (TSH) and thyroid autoantibodies in pregnant patients with thyroid disease at various stages of pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01 respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r = 0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA (enzyme linked immunosorbent assay) would form a useful first line test for thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies would aid in the diagnosis of autoimmune hypothyroidism.

Adult↗

PubMed1981

Thyroid disease in progressive systemic sclerosis: increased frequency of glandular fibrosis and hypothyroidism.

A series of patients with fatal progressive systemic sclerosis was reviewed with regard to pathologic, clinical, and serologic evidence of thyroid disease. Histologic evidence of severe fibrosis of the thyroid gland was found significantly more frequently in 56 progressive systemic sclerosis cases (14%) compared to an age and sex matched control autopsy series (2%) from the same institution. Based on determination of serum free thyroxine, free triiodothyroxine (T3), thyroid stimulating hormone, and reverse T3, 27 patients were classified as euthyroid (11), euthyroid sick (9), and hypothyroid (7). Patients with hypothyroidism more frequently had subcutaneous calcinosis. Raynaud's phenomenon, esophageal hypomotility, sclerodactyly, and multiple telangiectasias (the CREST syndrome variant of progressive systemic sclerosis); all thyroid glands from the hypothyroid patients had fibrosis, but lymphocytic infiltration was an infrequent finding. Six hypothyroid patients had high titers of serum antithyroid antibodies, suggesting autoimmune thyroid disease. Thyroid gland fibrosis and hypothyroidism, possibly of autoimmune pathogenesis, are thus frequent and often unsuspected findings in progressive systemic sclerosis.

Adult↗