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PubMed1987

[Genetic factors predisposing to autoimmune diseases. Study of HLA antigens in a family with pernicious anemia and thyroid diseases].

In a family including patients suffering from autoimmune disease (2 propositi: pernicious anemia and Graves' disease, pernicious anemia and autoimmune thyroiditis), we have determined common autoantibodies and tissue antigens (HLA) in 47 patients (26 males and 21 females) from 2 generations. In this family, we have found 4 cases of pernicious anemia, 5 cases of thyroid disease (2 Graves' disease), 3 women with repetitive abortions and 2 cases of melanoma. Patients with autoantibodies, often asymptomatic, are abnormally numerous (44% in generation II, 16% in generation III). A correlation with haplotype A1B8DR3 was found only for Graves' disease. Likelihood of forming autoantibodies appears to be of multifactorial origin. Its mode of transmission remains unknown.

Abortion, Habitual↗
PubMed2004

Diagnosis and management of thyroid disease and the critically ill patient.

OBJECTIVE: To review current concepts in the diagnosis and management of thyroid disease in the critically ill patient. DATA SOURCES: A review of articles reported on thyroid disease and the acutely ill patient. SUMMARY OF REVIEW: Normal thyroid function depends on an integrated response between the pituitary and thyroid gland to provide an appropriate circulating T4 level which is converted to T3 by peripheral tissues. Thyroid hormone increases oxygen consumption and regulates lipid and carbohydrate metabolism and normal growth and maturation of tissues. In patients with a severe non-thyroidal illness, the thyroid stimulating hormone (TSH), free thyroxine (FT4) and free 3,5,3-triiodo-L-thyronine (FT3) levels decrease. Dopamine, dobutamine or corticosteroid therapy may also reduce TSH levels. The TSH and T4 levels often return to low normal levels, although with continued severe illness they may remain low. The clinically euthyroid state is maintained in the presence of a reduction in FT3 levels partly due to an increase in synthesis of tissues T3 receptors. During the recovery phase of the illness, there is often a transient elevation in the TSH level until the FT4 and FT3 levels are returned to normal. There are no clinical data that have shown a consistent reduction in mortality with thyroid hormone treatment in the critically ill patient. In general, in the absence of clinical signs of thyroid disease, abnormal thyroid function tests should not be treated in the critically ill patient and thyroid function studies should be repeated after the acute illness has resolved. Hypothyroid and hyperthyroid states may present with acute cardiorespiratory failure. Treatment that includes cardiorespiratory resuscitation and thyroid hormone replacement in hypothyroid states and beta adrenergic blockers in hyperthyroid states will often allow correction of the underlying disorder to be achieved successfully. CONCLUSIONS: Abnormal thyroid function tests are commonly found in the critically ill patient and do not require treatment. However, hypothyroid and hyperthyroid states may present with acute cardiorespiratory failure and require careful and specific management strategies to resolve the thyroid disorder.

Journal Article↗
PubMed1979

[Incidence of thyroid diseases in primary hyperparathyroidism].

The incidence of thyroid diseases was evaluated in patients with primary hyperparathyroidism subjected to parathyroidectomy. Eleven patients (26.8%) were affected in this way: 2 with carcinoma, 5 with nodular goitre, and 4 with adenoma. The possible reasons for associations of this kind are discussed, and it is suggested that their high frequency points to a relationship of cause and affect.

Adenoma↗
PubMed1975

Ultrasonics in the diagnosis of thyroid disease.

Ultrasonic A scans of the thyroid have been carried out on 47 patients with suspected thyroid disease. It was possible to measure the antero-posterior diameter of each lobe and to identify whether the tissue was homogeneous, nodular or cystic. Measurement of individual nodules or cysts was accurate to within 5 mm when compared with the tissue removed at operation. Ultrasonic examination was able to differentiate other lumps, in the neck from those arising in the thyroid gland. It is concluded that ultrasonic examination of the thyroid is a useful adjunct to other conventional tests and deserves to be used more widely.

Adenoma↗
PubMed2000

Disclosing subclinical thyroid disease. An approach to mild laboratory abnormalities and vague or absent symptoms.

Patients with subclinical thyroid disease often have no apparent symptoms or only nonspecific complaints. However, increasing evidence that early disease is associated with behavioral, psychiatric, biochemical, and organ-specific abnormalities has led several specialty organizations to publish or modify position papers. Serum TSH testing is the most sensitive method of identifying early thyroid dysfunction. It should be considered in patients who have risk factors for mild thyroid failure, have symptoms that could be related to thyroid disease, or are taking exogenous thyroid hormone. T4 therapy should be strongly considered in patients with a TSH level of 10 mIU/L or more. If observation is elected in asymptomatic patients with lesser TSH elevation, periodic measurements are advised. In patients with TSH suppression who are taking thyroid hormone, the dose should be lowered. If the TSH level is decreased because of endogenous suppression and free-T4 and T3 levels are normal, options include observation and treatment with an antithyroid drug or thyroid ablation. Early therapy should be considered in older patients and those with heart disease or nodular thyroid disease. The goal of all treatment methods should be to keep the TSH level in the normal range.

Humans↗
PubMed1999

Peptides of human thyroglobulin reactive with sera of patients with autoimmune thyroid disease.

Autoantibodies to thyroglobulin (Tg) are a prominent feature of the two autoimmune thyroid diseases, chronic lymphocytic (Hashimoto's) thyroiditis and Graves' disease. Similar autoantibodies are found in the serum of many normal individuals without evidence of thyroid disease. Previous studies have indicated that patients with autoimmune thyroid disease recognize epitopes of Tg which are not usually recognized by normal individuals. The goal of this investigation was to identify peptide fragments of Tg bearing these disease-associated epitopes. For this purpose, we utilized a panel of mAbs that bind to different epitopes of the Tg molecule. One of these mAbs (137C1) reacted with an epitope that was also recognized by the sera of patients with autoimmune thyroiditis. In the present study, we show that two peptides (15 and 23 kDa) that reacted with mAb 137C1 are located in different parts of the Tg molecule. Each peptide inhibited the binding of mAb 137C1 to the other peptide and to the intact Tg, indicating that the same epitope was represented on the two peptides. Loops and helices of the secondary structure of the two peptides might be involved in the conformational epitope recognized by mAb 137C1. A striking finding of this study is that two apparently unrelated fragments of the Tg molecule bind to the same mAb. These findings may have important ramifications with regard to epitope spread and the progression of the autoimmune response to disease.

Amino Acid Sequence↗
PubMed2005

Thyroid disease in the elderly: sex-related differences in clinical expression.

Thyroid diseases are more prevalent in females. This notion is mostly derived from studies conducted in adult subjects, but the knowledge of the relationship between sex and thyroid disease is becoming important for the epidemiological study of aging population. Aging has been proposed to represent a trigger for the development of autoimmune phenomena resulting in the production of both organ- and non-organ-specific antibodies. Studies on the relationship between sex and thyroid autoimmunity in elderly subjects have shown that the age-related prevalence of antithyroid autoantibodies is greater in women >60 yr of age. An increased prevalence of hypothyroidism has been demonstrated in the elderly population. Several factors may affect prevalence, but virtually all studies report higher prevalence rates for either overt or subclinical hypothyroidism in women with advancing age. This gender-related difference, however, has not been demonstrated for hospitalized patients. Difficulties are encountered in the attempt to estimate a sex-related difference in the prevalence of hyperthyroidism in elderly subjects. In most cases, Graves' disease and toxic multinodular goiter represent the cause of the disease with relative proportions depending on iodine intake. However, data on the prevalence of this disorder and on its sex-related frequency are significantly affected by underlying nodularity and functional autonomy. This phenomenon may be even more pronounced when excess iodine intake occurs and when patients are treated with iodine-containing drugs and thyroid hormone therapy. Subclinical hyperthyroidism is more common in women than in men, especially in subjects >70 yr. Both overt and subclinical hyperthyroidism arise from underlying thyroid nodular disease. The low-T3 syndrome is common in the elderly. Due to the fact that the low-T3 syndrome is often derived from underlying diseases, it is difficult do define a sex-related difference in its prevalence. However, in unselected elderly home-dwellers, an independent association of low-T3 syndrome with male gender has been shown. Aging represents an important factor to define the aggressiveness of thyroid carcinomas. Both follicular and anaplastic histotypes of thyroid cancer are more frequently found in elderly subjects. In aging subjects, male sex seems to be highly correlated with the risk of thyroid cancer. In conclusion, epidemiological data from the aging population confirms that men are less affected by thyroid disease than women. However, male sex may represent a risk factor for thyroid cancer in elderly population and this observation should be carefully considered in the evaluation of thyroid nodules in the elderly.

Aged↗
PubMed1998

[A database for thyroid diseases: evaluation with special reference to potential consequences of a nuclear power plant accident].

The concept of a thyroid disease register based on a relational database system with a structured query language (SQL) is reported. More than 5000 examination findings of benign and malignant thyroid disorders have been recorded so far, covering the period from 1986 to 1996. For epidemiological studies these population-based thyroid diseases data can be allocated to a digital data map by means of the five-digit German postal code. When evaluating the data with regard to the function of the thyroid gland as an indicator of preceding nuclear power plant disasters and fallout, we found neither indicators of an increased incidence of thyroid carcinoma as an aftermath of the Chernobyl disaster nor the occurrence of clusters. The data were supplemented by the results of a survey among all Schleswig-Holstein pathologists involved in the diagnosis of thyroid diseases. Data on childhood carcinoma of the thyroid were also provided by the Childhood Tumor Register of the Institute of Pathology, University of Kiel, and by the Childhood Cancer Register of the University of Mainz.

Databases, Factual↗
PubMed2000

Thyroid disease in HCV carriers undergoing antiviral therapy with interferon plus ribavirin.

High prevalence of thyroid autoantibodies, with or without overt thyroiditis, has been described in hepatitis C patients, particularly in those undergoing alpha-interferon treatment. The aim of this study was to describe the frequency and clinical outcome of thyroid disease in a cohort of HCV carriers before and during combination therapy with interferon plus ribavirin. Between May, 1997, and May, 1999, 111 previously untreated (naive) patients were treated with a-interferon plus ribavirin for 6 or 12 months. Of those, 67 (60%) patients were male and 44 (40%) female. Thyroid function was evaluated in all patients by testing free T4, TSH and antiTPO within 30 days prior to treatment, 90 days after treatment was initiated, and 6 months after treatment was concluded. Abnormal thyroid tests were observed in 4 (3.6%) patients--1 male and 3 female--before the onset of antiviral treatment. Three patients were already undergoing T4 replacement due to Hashimoto thyroiditis and 1 patient had positive antiTPO with normal free T4 and TSH. All 4 patients completed the treatment regime for HCV, but required hormone replacement. Among the patients with a normal thyroid function test prior to treatment (107 cases), 5 (4.6%) developed thyroid test abnormalities; 2 patients had hypothyroidism due to autoimmune thyroiditis; 1 patient became positive for antiTPO antibodies but thyroid function remained normal, and 2 patients had subacute thyroiditis. Four of these patients (80%) were female and 1 was male (20%). A family history of thyroid disease was strongly predictive of thyroid abnormalities during antiviral treatment. In conclusion, there is a low prevalence of thyroid function abnormalities in HCV carriers with no prior antiviral treatment. Family history of thyroid disease reinforces the special attention to thyroid abnormality development before considering antiviral therapy. Subacute thyroiditis during combination therapy was observed, but its pathogenesis is still unknown. Evaluation of thyroid function during and after antiviral treatment is strongly recommended because thyroid related symptoms can be easily misinterpreted as medication side effects.

Adult↗
PubMed2006

Acquired neonatal thyroid disease due to TSH receptor antibodies in breast milk.

INTRODUCTION: We investigated whether thyroid receptor antibodies (TRAb) could result in transient neonatal thyroid disease by transfer through milk from mothers treated for thyrotoxicosis. AIM: To analyse whether breast milk content of TRAb in euthyroid mothers with treated thyrotoxicosis resulted in neonatal thyroid disease and whether extended breastfeeding prolonged the neonatal disease. PATIENTS: We tested three TRAb-positive mothers and the course, treatment and outcome for their offspring with neonatal thyrotoxicosis, and six healthy and two TRAb-negative euthyroid mothers with treated thyrotoxicosis during breastfeeding. METHOD: TRAb was analysed in serum and breast milk by a radioreceptor assay. RESULTS: TRAb in serum was detectable in all treated mothers, in one mother during her four pregnancies, resulting in all neonates requiring treatment for thyrotoxicosis. Serum TRAb concentration in neonates decreased continuously with time after birth. Breast milk TRAb was detectable in all cases but not in the controls or in TRAb-negative mothers treated for thyrotoxicosis. The calculated half-life for offspring serum and breast milk TRAb was calculated as approx. 3 weeks and 2 months, respectively. CONCLUSION: Euthyroid TRAb-positive mothers may cause transient neonatal thyroid disease which seems to be worse and more prolonged during breastfeeding as a consequence of TRAb in breast milk.

Adult↗
PubMed1993

[Evaluation of type IV collagen in patients with various thyroid disease].

Serum level of type IV collagen was measured in 104 patients with various thyroid disease, and the relationship between its level and thyroid hormone level was examined. The type IV collagen was measured by the method of one step sandwich enzyme immunoassay (EIA) using two distinct monoclonal antibodies recognized triple-helical (TH) domain and 7-S domain, respectively. The serum level of type IV collagen was significantly high in the hyperthyroid patients compared with that in normal controls, and a significant positive correlation was found between its value and thyroid hormone levels (T3, T4, FT3, FT4). The elevated level of type IV collagen in hyperthyroid patients was decreased to normal level, when they became to euthyroid after antithyroid drug therapy for hyperthyroidism. The serum level of type IV collagen was in normal range in hypothyroid patients, but the value was increased to high normal range after T4-replacement therapy for hypothyroidism. This evidence indicates that the serum level of type IV collagen is closely related to thyroid hormone level in patient with various thyroid disease. Type IV collagen concentration might be one of the useful variables for evaluating the thyroid function, although its mechanism is not elucidated.

Adult↗
PubMed1987

HLA-D subregion expression by thyroid epithelium in autoimmune thyroid diseases and induced in vitro.

Human thyroid epithelial cells (thyrocytes) express HLA Class II molecules in autoimmune thyroid diseases (ATD). Normal thyrocytes do not express Class II, but can be induced to do so by culture with interferon-gamma (gamma-IFN). We have examined HLA-D subregion expression in sections and monolayers of thyroid by indirect immunofluorescence using appropriate monoclonal antibodies. The results indicate that, in ATD, the incidence and intensity of Class II subregion expression by thyrocytes varies between patients, and follows the pattern DR greater than DP greater than DQ. The same hierarchy is observed in cultured normal thyrocytes treated with gamma-IFN: strong induction of Class II, and of DP and DQ in particular, requires relatively high concentrations of gamma-IFN or additional factors such as thyroid stimulating hormone. These findings suggest that HLA-D subregion expression by thyrocytes in on-going ATD is determined by the levels of disease related factors in the affected tissue.

Autoimmune Diseases↗
PubMed1986

Thyroid disease in patients with benign and malignant mastopathy.

The incidence of thyroid disease was examined prospectively in 97 consecutive patients with breast cancer (Group I) and was compared with that of 61 women with cystic breast disease (Group II) and that of 60 control women (Group III) with no breast problems. Thyroid enlargement was found in 47%, 49%, and 22% of those in Groups I, II, and III, respectively, and treatment with thyroid hormones was taken by 9.3% (I), 8.2% (II), and 5.0% (III) of the cases. The mean thyroid-stimulating hormone (TSH) concentration in those in Group I (5.4 +/- 2.2 microU/ml) was significantly higher than in Groups II (3.9 +/- 1.9, P less than 0.01) and III (4.0 +/- 1.8, P less than 0.001), whereas thyroid microsomal antibodies were detected in 13.4% (I), 9.1% (II), and 1.7% (III); mean triiodothyronine (T3) and thyroxin (T4) concentrations were similar in the three groups. When both TSH and T3 concentrations were taken into account, 24% and 17% of the patients, respectively, from Group I were no longer in the Group III range; the corresponding figures for Group II were 13% and 23%, respectively. These results indicate that breast cancer and thyroid disease are probably related, but not in a specific way, since benign mastopathy also seems to be associated with thyroid disturbances.

Adult↗
PubMed2006

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: pathology analysis of thyroid cancer cases in Ukraine detected during the first screening (1998-2000).

BACKGROUND: The Ukrainian American Cohort Study evaluated the risk of thyroid disorders in a group of individuals who were younger than age 18 years at the time of the Chornobyl (Chernobyl) accident. In this article, the authors describe the pathology of thyroid carcinomas detected in the first screening. METHODS: From 1998 to 2000, 13,243 individuals completed the first cycle of screening examinations. Eighty patients underwent surgery between 1998 and 2004. Intraoperative and postoperative pathologic studies were performed at the Institute of Endocrinology and Metabolism, Kyiv. RESULTS: Pathologic analysis revealed 45 thyroid carcinomas, including 43 papillary thyroid carcinomas (PTCs) (95.6%) and 2 follicular thyroid carcinomas (FTCs) (4.4%). TNM classification (5th edition) of the PTCs included 8 T1 tumors (18.6%), 16 T2 tumors (37.2%), and 19 T4 tumors (44.2%). Fifteen PTCs (34.9%) were N1a,N1b, and 3 PTCs (7.0%) were M1. Among the PTCs, 8 exhibited the classical papillary histologic pattern (18.6%), 14 exhibited a follicular histologic pattern (32.6%), 5 exhibited a solid histologic pattern (11.6%), and 16 exhibited a mixed histologic pattern (37.2%). Both FTCs had a microfollicular-solid structure. Eleven of 20 cohort members who underwent surgery before the first screening had PTCs. Regional metastases (63.6%) and distant metastases (18.2%) were more common in this group. CONCLUSIONS: Multifocal growth, lymphatic and blood vessel invasion, extrathyroid spread, and regional and distant metastases were more frequent in less differentiated PTCs (>30% solid structure). Small carcinomas (</=10 mm) comprised 23.3% of PTCs, and most of those (8 of 10 small carcinomas; 80%) were of the papillary-follicular subtype and therefore were more differentiated. The solid subtype of PTC was associated with shorter latency, especially in individuals who were diagnosed before the first screening. The histology of post-Chornobyl cancers is changing with time.

Adenocarcinoma, Follicular↗
PubMed2005

Thyroid disease in pregnancy and childhood.

The subject of thyroid disease in pregnancy is receiving increasing attention from many scientific disciplines. Thyroid function in pregnancy is characterised by a T4 surge at 12 weeks declining thereafter. Serum thyroid hormone concentrations fall in the second half of pregnancy but there are few data on normal reference ranges. Fetal brain development depends on T4 transport into the fetus which in turn depends on sufficient maternal iodine supply. There is current concern that adequate iodisation is not present in large parts of Europe. There is increasing evidence that thyroid autoimmunity is associated with fetal loss but the mechanism is unclear and therapy requires carefully conducted studies. While hyperthyroidism in pregnancy is uncommon, effects on both mother and child are critical if untreated. The use of propylthiouracil is recommended together with measurement of TSH receptor antibodies at 36 weeks gestation. Women receiving thyroxine therapy for hypothyroidism or as suppressive therapy should have their dose increased by up to 50% during pregnancy. There are now substantial data to show deleterious effects on child IQ resulting from low maternal T4 (or high TSH) during gestation. Major advances in molecular biology have contributed to elucidation of many genetic causes of congenital hypothyroidism. However, the aetiology of the majority of cases is still unclear and further research is required. The presence of TPO antibodies in about 10% of pregnant women in early gestation is a predictor of an increased incidence of subclinical hypothyroidism during pregnancy and also of postpartum thyroid dysfunction. The latter condition occurs in 5-9% of women and 25-30% progress to permanent hypothyroidism. This review suggests that screening for thyroid function in early pregnancy and levothyroxine intervention therapy for maternal subclinical hypothyroidism should be considered but evidence is awaited. Screening for both thyroid dysfunction and thyroid antibodies ideally at a preconception clinic but certainly in early gestation is recommended.

Antithyroid Agents↗
PubMed2002

["Subclinical" thyroid disease].

BACKGROUND: It is generally easy to diagnose and treat patients with thyroid diseases, though there has been considerable uncertainty over whether or not to treat patients with subclinical disease. MATERIAL AND METHODS: An overview of clinical symptoms and complications related to subclinical thyroid disease is presented on the basis of relevant literature. RESULTS: Patients with subclinical hypothyreosis (elevated TSH level and normal free T4) may benefit from treatment with thyroxine in relation to well-being, serum lipid levels, and possibly also blood pressure. Patients with subclinical hyperthyreosis (suppressed TSH level and normal free T4) have an increased risk of developing atrial fibrillation and possibly also dementia. INTERPRETATION: Subclinical thyroid disease is usually progressive. If a transient condition is ruled out, proper treatment should not be delayed.

Cardiovascular Diseases↗
PubMed1994

Molecular genetics of thyroid diseases.

Over the past 20 years, recombinant deoxyribonucleic acid technology has led to the cloning of three major thyroid specific protein genes (thyroglobulin, thyroperoxidase and thyrotrophin receptor), which happen to be also the main thyroid autoantigens implicated in thyroid diseases. In this context, the impact that molecular genetics has had on the understanding of aetiopathogeny and diagnosis of thyroid diseases is summarized, with special emphasis on a recently discovered genetic mechanism responsible for toxic nodules. One fruitful outcome of the basic research on thyroid-specific gene expression has been the possibility of targeting the expression of a series of genes to the thyroid in transgenic mice. The result is the availability of mouse models mimicking human thyroid diseases such as destructive hypothyroidism, hyperactive thyroid adenomas and thyroid cancers exhibiting varying levels of differentiation.

Animals↗