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[Surgical treatment of thyroid diseases in geriatric patients].

Thyroid diseases have a characteristic evolution in geriatric age, whether for the symptomatology frequently mingled with typical manifestations of again, or for glandular involution. Moreover, in the aged patient, the particular aspect of the epidemiology, physiopathology, clinic and therapy are to know and interpret. In most cases, the presence of a uni- or multi-nodular goiter does not cause compression problems or cancerization risk. In the presence of these problems and in multi-nodular goiter, we prefer total thyroidectomy because, at the present time, it is possible to put at zero the risks of this operation, neither we fear hypothyroidism which all the same also appears in less extensive operations. Between thyroid diseases, cancer has a typical biological behaviour and prognosis in geriatric patients. While most tumors have a better curability in geriatric age, these have a worse prognosis. So therapeutic indications very as a function of age. About this the authors present preliminary data of a prospective trial started in 1992.

Age Factors↗

Risk factors for and prevalence of thyroid disorders in a cross-sectional study among healthy female relatives of patients with autoimmune thyroid disease.

OBJECTIVE: Autoimmune thyroid disease (AITD) is a common disorder especially in women, and both genetic and environmental factors are involved in its pathogenesis. We wanted to gain more insight into the contribution of various environmental factors. Therefore, we started a large prospective cohort study in subjects at risk of developing AITD, for example healthy female relatives of AITD patients. Here we report on their baseline characteristics. SUBJECTS: Only first- or second-degree female relatives of patients with documented AITD were included. MEASUREMENTS: Smoking habits, oestrogen use, pregnancy history and iodine exposure were assessed by questionnaires, and correlated to the thyroid function and antibody status. RESULTS: Of 803 subjects, 440 came from families with more than one patient with documented AITD. Of these families, 33% had documented cases of both Graves' disease and Hashimoto's thyroiditis. Although the subjects were in self-proclaimed good health, 3.6% were found to have hypothyroidism (overt disease in 1.3%) and 1.9% had hyperthyroidism (overt disease in 0.4%). These patients were older than the euthyroid subjects and were mostly positive for thyroid peroxidase (TPO) antibodies. Oestrogen use was associated with a lower rate of hyperthyroidism [relative risk (RR) 0.169; 95% confidence interval (CI) 0.06-0.52], whereas having been pregnant was associated with a higher relative risk for hyperthyroidism (RR 6.88; 95% CI 1.50-30.96). Of the 759 euthyroid subjects, 24% had TPO antibodies. Smoking and oestrogen use were negatively correlated with the presence of TPO antibodies. In the euthyroid subjects, TPO antibody titre correlated positively with TSH levels (r = 0.386; P < 0.001). CONCLUSIONS: The high prevalence of evidence for autoimmune thyroiditis at baseline supports the importance of genetic factors in its pathogenesis. The co-occurrence of Hashimoto's thyroiditis and Graves' disease within one family suggests a common genetic basis for these diseases. Oestrogen use is associated with a lower risk, and pregnancy with a higher risk for developing hyperthyroidism. The positive correlation between TPO antibody titres and TSH levels in euthyroid subjects suggests that TPO antibodies are indeed a marker of future thyroid failure.

Adolescent↗

Is repeated fine-needle aspiration cytology useful in the management of patients with benign nodular thyroid disease?

Management of nonneoplastic thyroid nodules (TN) diagnosed by fine-needle aspiration (FNA) is controversial. While clinical follow-up with repeat FNA for enlarging TN is recommended in some studies, others recommend repeat FNA in follow-up of all benign TN after several months or years, in order to identify possible misdiagnosed malignant lesions. This study was done to determine the usefulness of repeat FNA in patients with benign nodular thyroid disease. We studied 94 fine-needle reaspirations performed on 43 females and 2 males 48.2 +/- 17 years of age with benign nodular thyroid nodular disease. Four patients had 3 consecutive FNAs and 41 patients had 2 consecutive FNAs. All FNAs were carried out by the same endocrinologist in the same thyroid area or by cytopathologists. The average time elapsed between the two consecutive FNAs was 18.3 +/- 11.2 (range, 4-48) months. Of the 45 patients, 23 presented with increase in size of the nodule and the remaining 22 patients did not have any change in size at the time of repeat FNA. Identical cytologic diagnoses were rendered in 39 of the 45 patients who underwent 2 or 3 consecutive FNA. Repeat FNA did not result in detection of any malignant neoplasms. Thyroid resection in 7 patients with increased nodule size and pressure symptoms confirmed the cytologic impressions of benign thyroid nodular disease. Our results show that the routine performance of repeated FNA cytology in the follow-up of patients with benign nodular thyroid disease with or without any clinical changes is of limited usefulness. Clinical factors rather than repeat FNA may hold precedence in surgical management of patients with benign nodular thyroid disease.

Adult↗

[Complications of extraintestinal endocrine disease associated with ulcerative colitis--association of ulcerative colitis and autoimmune thyroid disease].

We experienced a rare case of Basedow's disease followed by ulcerative colitis (UC). The association of UC and autoimmune thyroid disease was reviewed and discussed. A high frequency of endocrine autoimmunity, especially autoimmune thyroid disease, was reported in patients with UC. But prevalence of autoimmune thyroid disease associated with UC varies widely in different studies. Some authors described that it was impossible to say that the observed numbers of UC associated with thyroid disease exceed to those to be expected in a random sample of the general populations. The hypothesis that autoimmunity is important in the pathogenesis of UC and thyroid disease continues to stimulate interest. But the evidence for autoimmunity acting in these diseases is not quite as convinced. Further investigation is warranted to clarify the exact relationships between UC and thyroid disease.

Adult↗

Autoimmune thyroid disease in primary Sjögren's syndrome.

PURPOSE: To evaluate the prevalence of autoimmune thyroid disease and thyroid dysfunction in patients with primary Sjögren's syndrome. PATIENTS AND METHODS: Thyroid function of 33 patients with primary Sjögren's syndrome was clinically and biochemically evaluated. Thyroid hormones and autoantibodies against thyroid peroxidase, thyroglobulin, and thyroid hormones were measured. RESULTS: Autoimmune thyroid disease and thyroid dysfunction were found in 15 cases (45%): autoimmune thyroiditis in 8 (24%); autoimmune hyperthyroidism in 2 (6%); and reversible iodine-induced hypothyroidism in the remaining 5 (15%). One or more of the evaluated autoantibodies were detected in 8 euthyroid patients (24%). Overall, the prevalence of autoantibodies against thyroid peroxidase, thyroglobulin, thyroxine, and triiodothyronine was 45%, 18%, 42%, and 36%, respectively. CONCLUSIONS: The high prevalence of autoimmune thyroid disease and thyroid dysfunction found in primary Sjögren's syndrome, using sensitive immunologic and thyroid function tests, suggest that both diseases are more frequently associated than it was previously thought, and should be sought clinically and by laboratory tests in all patients with primary Sjögren's syndrome.

Adult↗

[ABC of thyroid diseases and their treatment].

Thyroid diseases are caused by a disturbance of thyroid hormone secretion, inflammations or tumors of the thyroid or combinations thereof. Most important causes for hyperthyroidism are Graves' disease and toxic nodular goiters (including toxic adenomas). Hypothyroidism is often caused by Hashimoto's chronic thyroiditis and can occur in patients after thyroidectomy. Chronic hashimoto's thyroiditis and subacute de Quervain's thyroiditis are the thyroid inflammations most frequently seen. Graves' disease and Hashimoto's thyroiditis are autoimmune thyroid diseases. Thyroid tumors encompass benign solitary nodules, diffuse and nodular goiters, papillary, follicular, medullary and anaplastic carcinomas.

Diagnosis, Differential↗

Epidemiology of thyroid diseases in iodine sufficiency.

Epidemiology of thyroid diseases in iodine-sufficient areas (ISA) deals with sporadic goiter, thyroid autoimmune diseases, and thyroid cancer. A comparison between the different studies performed is difficult because methods have changed over time and selection criteria and definitions such as prevalence or incidence were not used consistently by some authors. Sporadic goiter: in ISA, autoimmune processes play a major role in the development of sporadic goiter. In adults, sporadic diffuse goiter is most frequent in young women (16%), perhaps due to additional relative iodine deficiency especially in pregnancy, and declines with age (<10%). Sporadic nodular goiter increases from 5% in young women to 9% in older women. Autoimmune thyroid disease (AITD): thyroid autoantibodies (TAb) and histopathological lymphocytic infiltration of the thyroid is much more common in ISA (4.6% in women; 1.1% in men) than in iodine-deficient areas (IDA). The prevalence and incidence of hypothyroidism and hyperthyroidism varies, depending on whether overt and subclinical forms are included and whether newly or previously diagnosed dysfunction is considered. In an overview of the literature, the prevalence is 2 in 1000 for overt and 6 in 1000 for subclinical hyperthyroidism in ISA. The values for hypothyroidism are 5 in 1000 and 15 in 1000, respectively. Change from IDA to ISA: in former IDA, the percentage of hyperthyroidism increases up to 4 years after salt iodination. Whereas this effect is transient for Plummer's disease, a change from IDA to ISA seems to lead to a permanent increase in overt and subclinical Graves' disease. Thyroid cancer: most studies demonstrate that the histopathological types of thyroid cancer are different in IDA and ISA. There is a tendency toward an increase in differentiated and decrease of anaplastic cancer. The ratio of papillary to follicular thyroid cancer ranges from 6.5:1 to 3.4:1 in areas with high iodine intake, decreases 3.7:1 to 1.6:1 in areas with moderate iodine intake, and ranges from 1.7:1 to 0.19:1 in IDA.

Adult↗

Autoimmune thyroid diseases and coeliac disease.

BACKGROUND: Coeliac disease may be associated with a wide variety of diseases of known or suspected immunological aetiology. OBJECTIVE: To screen for both (a) the prevalence of coeliac disease in adults with autoimmune thyroid diseases, and (b) thyroid impairment among adults with coeliac disease, as compared to sex- and age-matched controls. DESIGN: Prospective cohort study. SETTING: University teaching hospital. PATIENTS: A total of 152 consecutive adults with autoimmune thyroid diseases, 185 consecutive coeliac disease patients (53 newly diagnosed and 132 already on a gluten-free diet) and 170 sex- and age-matched controls. METHODS: Screening for coeliac disease was done by means of IgA anti-endomysium antibodies, detected by indirect immunofluorescence on monkey oesophagus. Patients with positive sera underwent duodenal biopsy for diagnostic confirmation. Thyroid function was assessed by measuring the levels of serum thyroid-stimulating hormone, free T3, free T4, thyroperoxidase and thyroid microsome antibodies. Autoimmune thyroid diseases were classified according to the American Thyroid Association guidelines. RESULTS: Anti-endomysium antibodies were positive in five of 152 autoimmune thyroid disease patients (3.3%) and coeliac disease was histologically confirmed in all: this prevalence is 10-fold higher than expected. Only one patient presented with gastrointestinal complaints, but iron deficiency was found in three and alterations at bone mineralometry in all. The overall prevalence of autoimmune thyroid diseases was significantly higher (38/185, 20.5%) in coeliac patients than in controls (19/170, 11.2%). The prevalence of both hypo- and hyperthyroidism was not different from that of controls, while the prevalence of autoimmune thyroid disease with euthyroidism was 13% in patients and 4.7% in controls. CONCLUSIONS: The association of coeliac disease with autoimmune thyroid disease is not surprising as they share common immunopathogenetic mechanisms. It is advisable to screen autoimmune thyroid disease patients for coeliac disease as there is an increased risk for gluten intolerance. In contrast, thyroid function assessment in coeliac disease patients is probably less justified, although the need for a strict clinical follow-up of those patients with euthyroidism and autoimmune thyroid disease, who could develop overt thyroid impairment, remains an open question.

Adolescent↗

Intrathyroidal CD4+ T lymphocytes express high levels of Fas and CD4+ CD8+ macrophages/dendritic cells express Fas ligand in autoimmune thyroid disease.

In autoimmune thyroid disease (AITD), the proportion of CD4 lymphocytes is lower in the thyroid than in the peripheral blood. We examined both Fas and Fas ligand (FasL) expression in lymphocyte subsets and nonlymphoid mononuclear cells including monocytes, macrophages, and dendritic cells (M/DCs) in both peripheral blood and thyroid specimens from 11 patients with Graves' disease and 1 with Hashimoto's disease by three-color flow cytometry. Proportions and intensities of Fas expression were increased in CD4 single-positive (SP) (CD4(+) CD8(-)), CD8 SP (CD8(+) CD4(-) ), and CD4(+) CD8(+) double-positive (DP) lymphocytes in AITD thyroids compared to those in blood, and were much higher in CD4(+) (CD4 SP and DP) lymphocytes than in CD8 SP lymphocytes in the thyroid. In the blood, most M/DCs expressed only CD4, but approximately 60% of M/DCs expressed both CD4 and CD8 in AITD thyroid. The proportion of DP M/DCs expressing FasL was higher in thyroid than in blood; proportion and intensity of FasL expression were much higher in DP M/DCs than in CD4 SP and CD8 SP M/DCs in the thyroid. These data indicate that increased Fas expression in intrathyroidal CD4(+) T lymphocytes may be the cause of CD4 lymphocyte reduction in AITD thyroid, and that intrathyroid DP M/DCs with high FasL expression may be related to the reduction in AITD.

Adult↗

Lack of disease associated HLA-DQ restriction fragment length polymorphisms in families with autoimmune thyroid disease.

Autoimmune thyroid disease (AITD) is often familial and serological HLA disease associations have been described in many different populations. However, such HLA disease associations are weak and the precise molecular contribution of HLA antigens to thyroid disease susceptibility remains unknown. Much of the data available are cross-sectional and few studies have explored familial inheritance of AITD at the molecular level. We have, therefore, examined the inheritance of AITD in multiplex and multi-generational families using restriction fragment length polymorphism (RFLP) analysis of DNA digested with the restriction enzyme BamH1 and probed with a full length human HLA-DQ beta cDNA probe. Thirty seven subjects in 7 informative families were available for study. Eleven subjects had Graves' disease and 4 were diagnosed as having Hashimoto's thyroiditis. Segregation of polymorphic fragments enabled genotyping of each individual to produce fully informative families. LOD scores were computed, using the LIPED program, for dominant and recessive models of inheritance, for recombination fractions of 0.01 to 0.5 for each sex, and for penetrances of 0.1 to 1.0. The results showed that maximum LOD scores were negative for all of the inheritance models tested. If the primary locus for AITD were in the HLA region, LOD scores would be highly positive. These data, therefore, provide strong evidence against a disease locus for AITD in linkage disequilibrium with the HLA-DQ beta locus.

Adult↗

[The assessment of usefulness of humoral markers estimation in patients with autoimmune thyroid diseases].

UNLABELLED: Autoimmune thyroid diseases (AITD) constitute a group of the most common disorders caused by autoaggression of the immune system, comprising up to 1.5% of the human population. That is why optimalisation of diagnostics of Hashimoto thyroiditis (ChH) and Graves' disease (ChG) is an important issue. Aim of the study was to assess usefulness of humoral markers estimation: antithyroperoxidase antibodies (anty-TPO), antithyreoglobulin antibodies (anty-TG) and antithyroropin receptor antibodies (anty-TSHR). MATERIAL AND METHODS: The study was carried out in 5 groups of subjects: 1/14 patients with GD in euthyreosis on methimazol (Geu) 2/20 patients with hyperthyroid GD (Ghiper) 3/15 patients with ChH in euthyreosis on levothyroxine (Heu) 4/16 patients with hypothyroid ChH (Hhipo) 5/12 healthy volunteers age and sex-matched to group 1-4. The serum levels of anty-TPO and anty-TG were determined by the ELISA kit. Anty-TSHR were measured by the RIA method. RESULTS: The highest level of anty-TPO were observed in Hhipo group: 2.81 IU/I (1.79-3.22) (p<0.001 vs controls, p<0.05 vs ChH in euthyreosis). Among ChG patients higher values of anty-TPO were found in Ghiper group: 1.87 IU/I (0.68-2.88) (p<0.01 vs controls, p<0.05 vs ChG in euthyreosis). In ChH patients a positive correlation was observed between serum TSH and anty-TPO (R=0.47, p<0.01). In studied groups it was found a positive correlation between anty-TPO and anty-TG. Levels of anty-TG were increased in all studied patients as compared to controls, however there were no significant differences in anty-TG values between the groups. The highest concentration of anty-TSHR were found in Ghiper group: 6.71 (3.92-11.32) (p<0.001 vs controls, p<0.001 vs ChG in euthyreosis). There was a significant difference in anty-TSHR concentration between ChH groups: Hhipo i Heu (p<0.05). There was a negative correlation between serum TSH and anty-TSHR level in ChG patients (R=-0.05, p<0.001). CONCLUSIONS: In diagnostics of humoral markers in patients with AITD the most valuable in clinical practice is estimation of antithyroperoxidase antibodies serum level in Hashimoto thyroiditis and antithyroropin receptor antibodies serum concentration in Graves' disease.

Adult↗

IgA and IgG antigliadin, IgA anti-tissue transglutaminase and antiendomysial antibodies in patients with autoimmune thyroid diseases and their relationship to thyroidal replacement therapy.

Celiac disease is a chronic illness of the small bowel caused by gliadin intolerance in genetically predisposed subjects. The aim of this study was to investigate serum levels of IgA and IgG antigliadin antibodies, IgA antiendomysial antibodies, and IgA anti-tissue transglutaminase antibodies in 169 patients with autoimmune thyroid diseases, i.e. chronic thyroiditis and Graves' disease. Antiendomysial antibodies were positive in 2 out of 169 persons (1.18%), IgA antigliadin antibodies in 15.98%, IgG antigliadin antibodies in 51.48%, and IgA anti-tissue transglutaminase in 14.79%. The prevalence of positivity was higher compared to the 1312 control blood donors described in our previous study (Vancíková et al. 2002) (p<0.05). Patients with chronic thyroiditis treated with a high replacement dosage of levothyroxin (125-200 microg daily) had higher serum levels of IgA antigliadin antibodies in comparison with patients treated with a lower dosage (50-100 microg daily) (medians: 13.00 vs. 19.69, p=0.033). We found a negative correlation of IgA anti-tissue transglutaminase antibodies and total calcium serum levels (r = -0.480, p=0.0236, n=22). We can conclude that in persons with autoimmune thyropathy there is a high prevalence of positive antigliadin, anti-tissue transglutaminase and antiendomysial antibodies. Latent celiac disease may lead to impaired resorption of therapeutically administered levothyroxine, calcium, or other substances.

Adolescent↗

A genome-wide screen in 1119 relative pairs with autoimmune thyroid disease.

CONTEXT: Autoimmune thyroid diseases (AITD), comprising Graves' disease and autoimmune hypothyroidism, are characterized by loss of immunological self-tolerance to thyroid antigens. These are complex diseases arising from a combination of genetic and environmental factors. An understanding of the genetic susceptibility factors for AITD could help to target treatments more effectively and identify people at risk for these conditions. OBJECTIVE: The objective of this study was to identify regions of genetic linkage to AITD that could potentially harbor genetic susceptibility factors for these conditions. DESIGN: The study design was a genome-wide screen performed on affected relative pairs with AITD. SETTING: Patients were recruited through hospital endocrinology clinics. PARTICIPANTS: Some 1119 Caucasian relative pairs affected with AITD (Graves' disease or autoimmune hypothyroidism) were recruited into the study. INTERVENTION: Blood samples were obtained from each participant for DNA analysis, and clinical questionnaires were completed. MAIN OUTCOME MEASURE: The study aimed to identify regions of genetic linkage to AITD. RESULTS: Three regions of suggestive linkage were obtained on chromosomes 18p11 (maximum LOD score, 2.5), 2q36 (maximum LOD score, 2.2), and 11p15 (maximum LOD score, 2.0). No linkage to human leukocyte antigen was found. CONCLUSIONS: The absence of significant evidence of linkage at any one locus in such a large dataset argues that genetic susceptibility to AITD reflects a number of loci, each with a modest effect. Linkage analysis may be limited in defining such loci, and large-scale association studies may prove to be more useful in identifying genetic susceptibility factors for AITD.

Chromosome Mapping↗

Subclinical thyroid disease.

The term subclinical thyroid disease is used to describe asymptomatic thyroid abnormalities found on imaging studies or laboratory tests. Thyroid nodules not palpable on physical examination but detected on imaging studies performed for other purposes are called incidentalomas. In the absence of risk factors for thyroid cancer, nodules that are less than 1 cm in diameter do not require biopsy. Subclinical hyperthyroidism is defined as suppressed serum sensitive thyrotropin (TSH) and normal serum thyroxine and triiodothyronine levels. This condition may adversely affect the heart and the bones and should be treated, especially in patients older than 60 years. Subclinical hypothyroidism, defined as mildly elevated serum TSH and normal serum thyroxine levels, is the most common thyroid dysfunction. In patients with subclinical hypothyroidism, thyroxine therapy should be given if the serum TSH level is higher than 10 mIU/L. For TSH values between 5 and 10 mIU/L, the decision for therapy should be individualized and depends on the level of TSH, presence of antithyroid antibodies, and clinical factors.

Aged↗

Subclinical thyroid disease.

Subclinical thyroid dysfunction is defined as an abnormal serum thyroid-stimulating hormone level (reference range: 0.45 to 4.50 microU per mL) and free thyroxine and triiodothyronine levels within their reference ranges. The management of subclinical thyroid dysfunction is controversial. The prevalence of subclinical hypothyroidism is about 4 to 8.5 percent, and may be as high as 20 percent in women older than 60 years. Subclinical hyperthyroidism is found in approximately 2 percent of the population. Most national organizations recommend against routine screening of asymptomatic patients, but screening is recommended for high-risk populations. There is good evidence that subclinical hypothyroidism is associated with progression to overt disease. Patients with a serum thyroid-stimulating hormone level greater than 10 microU per mL have a higher incidence of elevated serum low-density lipoprotein cholesterol concentrations; however, evidence is lacking for other associations. There is insufficient evidence that treatment of subclinical hypothyroidism is beneficial. A serum thyroid-stimulating hormone level of less than 0.1 microU per mL is associated with progression to overt hyperthyroidism, atrial fibrillation, reduced bone mineral density, and cardiac dysfunction. There is little evidence that early treatment alters the clinical course.

Algorithms↗

The development of ischemic heart disease in relation to autoimmune thyroid disease in a 20-year follow-up study of an English community.

The original Whickham Survey documented risk factors for cardiovascular disease and the prevalence of thyroid disorders in a sample of 2779 adults that closely matched the British population. A 20-year follow-up study has determined outcomes in terms of morbidity and mortality from ischemic heart disease in over 97% of the original survey population. Analysis of deaths from all causes and from ischemic heart disease showed no association with antithyroid antibody status identified at first survey. A multiple logistic regression using the development of ischemic heart disease in the total population at follow-up as the dependent variable found that the significant predictor variables for men were age, cholesterol, mean arterial blood pressure, smoking history, and skinfold thickness index. For women only age, cholesterol, and mean arterial blood pressure were significant. The presence of autoimmune thyroid disease, as defined by either hypothyroidism, positive antithyroid antibodies, or raised serum thyrotropin at first survey, was not significant. A retrospective cohort study of a subsample of women identified at first survey with positive antithyroid antibodies or raised serum thyrotropin and closely matched controls found no significant association with mortality or development of ischemic heart disease. There is no evidence from this study to suggest that evidence of autoimmune thyroid disease identified 20 years ago is associated with an increased risk of ischemic heart disease.

Adolescent↗