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[A combination of thyroid diseases with a neoplastic process in the thyroid tissue].

Altogether 252 case records of patients operated on for thyroid cancer were analyzed to determine the frequency of combination of a neoplastic process with autoimmune thyroiditis. Analysis of morphological findings of the operative material has shown that thyroid cancer in autoimmune thyroiditis occurs 2.5-times less than in adenomatous goiter and 1.5-times less in diffuse toxic goiter. The resultant conclusion is that the combination of thyroid cancer with autoimmune thyroiditis occurs more seldom than cancer with diffuse toxic goiter and adenomatous goiter, and the combination of autoimmune thyroiditis with diffuse toxic goiter and adenomatous goiter occurs more frequently than that with thyroid cancer.

Adult↗
PubMed2003

Autoimmune thyroid disease and celiac disease in children.

BACKGROUND: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. METHODS: Five hundred seventy-three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty-three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty-six of the patients with CD (median age, 9 years) had been following a gluten-free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti-TSH receptor antibodies, and thyroid echographic pattern were considered. RESULTS: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten-free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty-four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). CONCLUSIONS: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten-free diet, may justify a thyroid status assessment at diagnosis and at follow-up evaluation of children with CD.

Adolescent↗
PubMed1987

Distribution of thyroid diseases and evaluation of laboratory parameters used in their diagnosis.

A retrospective rationalization of commonly performed tests and procedures for the assessment of patients with suspected thyroid disease was attempted. The final diagnosis, in 392 consecutive new referrals to a central thyroid clinic, was primarily established by combined criteria of clinical/scintigraphic/cytopathologic findings. Detailed statistical analysis and evaluation of the accumulated data have demonstrated that: (a) only 15.8% of patients exhibited measurable thyrometabolic disturbances, thus indicating a rather limited scope for the application of laboratory tests in screening for thyroid diseases; (b) the measurement of serum total thyroxine with the thyroid hormone uptake test and the derivation of the free thyroxine index constitute, at present, the most appropriate initial in vitro laboratory procedure for assessing thyrometabolic function; and (c) recently available innovative methods for estimating serum levels of free thyroid hormones have no advantages over established assays.

False Negative Reactions↗
PubMed2005

Iodine excretion in regions of Ukraine affected by the Chornobyl Accident: experience of the Ukrainian-American cohort study of thyroid cancer and other thyroid diseases.

Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 microg/L, 95% confidence interval (CI) 46.5-48.9 microg/L versus 41.7 microg/L, 95% CI 40.4-42.5 microg/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases.

Adolescent↗
PubMed2000

Analysis of heat shock protein polymorphisms in a large family with autoimmune thyroid diseases.

Graves disease and Hashimoto's thyroiditis are autoimmune thyroid diseases (AITD) in which the genetic contribution is complex. The purpose of this work was to analyze the influence of hsp70 gene polymorphisms on the susceptibility to AITD. The hsp 70-2 and hsp 70-hom polymorphism was analyzed, by PCR-RFLP using PstI and NcoI enzymes, respectively, in 40 patients affected with AITD and 38 related healthy individuals belonging to a large consanguineous family named Akr. The transmission disequilibrium test (TDT) was applied on nuclear families, deduced from the Akr pedigree, with at least one heterozygous parent for each studied polymorphism. The corresponding x2 values for hsp 70-2 and hsp 70-hom were, respectively, of 0.52, p > 0.05 and 2.77, p > 0.05. Our data indicated lack of association between these hsp polymorphisms and AITD in this large family.

Consanguinity↗
PubMed2001

An immune defect causing dominant chronic mucocutaneous candidiasis and thyroid disease maps to chromosome 2p in a single family.

We describe a large family in which a combination of chronic mucocutaneous candidiasis (fungal infections of the skin, nails, and mucous membranes) and thyroid disease segregate as an autosomal dominant trait with reduced penetrance. The family includes (a) four members with both candidiasis and thyroid disease, (b) five members, including one pair of phenotype-concordant MZ twins, with candidiasis only, and (c) three members with thyroid disease only. A whole-genome scan using DNA samples from 20 members of the family identified a candidate linkage region on chromosome 2p. By sampling additional individuals and genotyping supplementary markers, we established linkage to a region of approximately 15 cM bounded by D2S367 and D2S2240 and including seven adjacent markers consistent with linkage. With a penetrance estimate of.8, which was based on pedigree and affected status, the peak two-point LOD score was 3.70 with marker D2S2328, and the peak three-point LOD score was 3.82. This is the first linkage assignment of a dominant locus for mucocutaneous candidiasis.

Adult↗
PubMed2000

Does thyroid stunning exist? A model with benign thyroid disease.

With regard to the treatment of differentiated non-medullary thyroid carcinoma, there is controversy over whether radiation from a diagnostic radioiodine (131I) application really does have a suppressive effect on the uptake of subsequent therapeutic 131I (so-called thyroid stunning). However, inherent difficulties in exact remnant/metastatic tissue volumetry make it difficult to quantify how much diagnostic 131I is actually absorbed (absorbed energy dose) and hence to decide whether a threshold absorbed dose exists beyond which such stunning would occur. Since in benign thyroid disease the target volume can be readily quantified by ultrasonography, we sought to determine definitely whether stunning of thyroid cells occurs upon a second application of radioiodine 4 days following the first one. We therefore studied 171 consecutive patients with benign thyroid disease (diffuse goitre, Graves' disease, toxic nodular goitre) who received two-step 131I therapy during a single in-patient stay. For application of both calculated 131I activities we performed kinetic dosimetry of 131I uptake, effective half-life and absorbed dose. At the second application, patients showed significant stunning (a 31.7% decrease in 131I uptake, from 34.7% +/- 15.4% at first application to 23.7% +/- 12.3% at second application, P < 0.0005) without a significant difference in effective half-life (4.9 +/- 1.3 vs 5.0 +/- 1.7 days, P > 0.2). ANOVA showed that the extent of stunning was influenced significantly only by the absorbed energy dose at first application (F = 13.5, P < 0.0005), while first-application 131I activity, target volume, gender and thyroid function had no influence (all F < or = 0.71, all P > 0.4). There was no significant correlation between extent of thyroid stunning and first-application 131I activity ( r = 0.07, P > 0.3), whereas there was a highly significant correlation between thyroid stunning and first absorbed energy dose (r = 0.64, P < 0.00005), the latter correlation fitting a logarithmic model best. Multivariate factor analysis also revealed first absorbed energy dose to be the only decisive stunning factor. In conclusion, our study confirms that stunning exists in benign thyroid conditions and that it is a purely radiobiological inhibitory phenomenon related to absorbed dose.

Adult↗
PubMed1985

Thyroid carcinoma in benign thyroid diseases. An analysis from minute carcinoma.

The relative frequency of thyroid carcinoma in benign thyroid diseases such as toxic diffuse goiter (toxic goiter), adenomatous goiter (goiter), adenoma, and chronic thyroiditis (thyroiditis) was studied using 3,219 surgically removed thyroid glands. Coexistence of carcinoma and benign diseases was found in 257 glands. Among them, 157 glands had minute carcinoma (diameter of cancer nodule is smaller than 10 mm) and 100 glands had advanced carcinoma (larger than 10.1 mm in diameter). The incidence of carcinoma including minute carcinoma was 29.4% in goiter (98/333), 21.0% in thyroiditis (11/53), 8.6% in adenoma (55/638), and 5.3% in toxic goiter (98/1852). Chi-square test also revealed that the rate of carcinoma not only advanced carcinoma but also minute carcinoma was higher in goiter than in the other diseases (P less than 0.01, respectively). Among the patients aged under 39, the incidence of advanced carcinoma and minute carcinoma in thyroiditis were the highest, respectively (83% and 100% in thyroiditis, 9.0% and 11.4% in goiter, 2. 6% and 1.9% in adenoma, and 0.7% and 3.4% in toxic goiter), however, among the patients aged over 40, they were secondary lower and the lowest, respectively (19% and 16.8% in goiter, 5.2% and 7.5% in adenoma, 4.2% and 6.7% in thyroiditis, and 1.4% and 7.5% in toxic goiter). We concluded that adenomatous goiter accompanies carcinoma more frequently than other benign thyroid diseases and the high incidence of carcinoma in chronic thyroiditis is probably due to a preoperative selection of the patients.

Adenoma↗
PubMed2003

Association of a rare thyroglobulin gene microsatellite variant with autoimmune thyroid disease.

Genetic and environmental factors contribute to the development of Graves' disease and Hashimoto's thyroiditis. These diseases, although clinically distinct, share many immunological and histological features. Susceptibility genes for autoimmune thyroid disease (AITD) have been investigated, although only the human leukocyte antigen and cytotoxic T lymphocyte-associated antigen-4 gene regions have been consistently associated with disease. Recent data, however, have shown linkage and association of chromosome 8q24 (containing the thyroglobulin gene) to AITD. Therefore, we performed a case-control association study on patients with AITD and controls using previously associated markers (D8S284 and Tgms2). No differences in allele frequencies were observed between AITD cases and controls for D8S284. Compared with the three common alleles (frequencies >10%), the rare alleles of Tgms2 were increased (chi(2)= 10.6; P = 0.001) at Tgms2. This group included the 336-bp allele (increased in cases vs. controls: chi(2)= 24.97; P < 0.001), which has previously been reported to be associated with AITD. The rarity of this allele in the United Kingdom, however, precluded analysis in our family dataset. Although these findings may represent a random chance event, in view of previous reports of linkage and association of this gene region to AITD, this may be an example of a rare causal variant of a complex disease.

Adolescent↗
PubMed1985

A high prevalence of thyroglobulin autoantibodies in adults with and without thyroid disease as measured with a sensitive solid-phase immunosorbent radioassay.

Sera from 228 patients with thyroid disease and 140 healthy subjects without clinical or biochemical evidence of thyroid disease, were tested using a sensitive solid-phase immunosorbent radioassay (RIA) and a passive hemagglutination test (TRC test) for thyroglobulin antibodies (Tg-ab). With the RIA technique, Tg-ab was found in 27% of the controls (36% of the women and 15% of the men), whereas only 0.7% of them were Tg-ab positive with the TRC test. All individuals with primary hypothyroidism were Tg-ab positive with the RIA, compared with only 56% with the TRC test. Tg-ab (RIA) were found in 43/53 (81%) of the patients with toxic diffuse goiter, and in 30-40% of the patients with toxic nodular goiter, toxic adenoma, atoxic goiter, and thyroid carcinoma, the TRC test being positive in 10-17% of these patients. The high prevalence of Tg-ab in the healthy population suggests that subclinical thyroiditis is more frequent than has been assumed from antibody measurements made with less sensitive methods, and is in agreement with the prevalences reported from autopsy studies.

Adult↗
PubMed2004

Unravelling the genetic complexity of autoimmune thyroid disease: HLA, CTLA-4 and beyond.

The autoimmune thyroid diseases (AITDs) including Graves' disease (GD) and autoimmune hypothyroidism (AIH) are the commonest of the autoimmune conditions affecting 2-5% of the western population. Twin studies have clearly demonstrated that AITDs are caused by a combination of both environmental and genetic factors. Association of the HLA class II region with AITD has been documented for over 20 years now, but the primary aetiological variant in this region remains unknown. More recently the CTLA-4 gene region has been identified as the second locus conferring susceptibility to AITD. In contrast to HLA, a polymorphism of the CTLA-4 gene, which encodes an important negative regulator of the immune system, has been identified as a candidate for a primary determinant for AITD. A large number of candidate gene and genome wide linkage studies have been involved in the search for the elusive 'third' locus. The thyroglobulin (Tg) gene in humans maps to chromosome 8q, which has been linked in family studies to AITD. A number of association studies in humans and the mouse model for AITD are beginning to implicate the Tg gene although convincing evidence for a primary causative role is still needed. The establishment of large DNA disease resources along with more detailed genetic maps and the development of faster, more effective, high throughput genotyping and sequencing methods, provides some sense of optimism that novel loci will be identified in the near future and the complex aetiology of AITD will be further unraveled.

Animals↗
PubMed2001

Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl.

We evaluated the incidence of childhood thyroid diseases and urinary iodine levels in Nagasaki, Japan and in Gomel, Belarus, which was greatly radio-contaminated by the Chernobyl accident, in order to obtain the comparative data of thyroid diseases between iodine-rich (Japan) and -deficient (Belarus) areas. In Nagasaki, the median level of urinary iodine, measured by ammonium persulfate digestion in microplate method, was 362.9 microg/L. In order to evaluate the geographical differences in Japan, other samples were collected in Hamamatsu and in South Kayabe, Hokkaido, where the median levels were 208.4 microg/L and 1015.5 microg/L, respectively. Furthermore, thyroid screening by ultrasound (US) in Nagasaki revealed only four cases that showed goiter (1.6%) and two cases (0.8%) that had cystic degeneration and single thyroid cyst. There was no evidence of thyroid nodule detected by US examination. In contrast, the median of urinary iodine level was 41.3 microg/L in Gomel. The incidences of goiter (13.6%) and echogenic abnormality (1.74%) in Gomel were much higher than in Nagasaki, suggesting the critical involvement of iodine deficiency in increased childhood thyroid abnormality around Chernobyl. Radioactive iodine released just after the Chernobyl accident may have influenced predominantly children residing in iodine-deficient areas. Our results suggest that management of thyroid screening for schoolchildren at ordinary times may be beneficial for monitoring the adverse effects of radioactive iodine from the standpoint of future prospective study.

Adolescent↗
PubMed2001

Lack of association between estrogen receptor beta dinucleotide repeat polymorphism and autoimmune thyroid diseases in Japanese patients.

BACKGROUND: The autoimmune thyroid diseases (AITDs), such as Graves' disease (GD) and Hashimoto's thyroiditis (HT), appear to develop as a result of complex interactions between predisposing genes and environmental triggers. Susceptibility to AITDs is conferred by genes in the human leukocyte antigen (HLA) and genes unlinked to HLA, including the CTLA-4 gene. Recently, estrogen receptor (ER) beta, located at human chromosome 14q23-24.1, was identified. We analyzed a dinucleotide (CA)n repeat polymorphism located in the flanking region of ERbeta gene in patients with AITDs and in normal subjects. High heterozygosity makes this polymorphism a useful marker in the genetic study of disorders affecting female endocrine systems. We also correlated a ERbeta gene microsatellite polymorphism with bone mineral density (BMD) in the distal radius and biochemical markers of bone turnover in patients with GD in remission. RESULTS: Fourteen different alleles were found in 133 patients with GD, 114 patients with HT, and 179 controls subjects. The various alleles were designated as allele*1 through allele*14 according to the number of the repeats, from 18 to 30. There was no significant difference in the distributions of ERbeta alleles between patient groups and controls. Although recent study demonstrated a significant relation between a allele*9 in the ERbeta gene and BMD in postmenopausal Japanese women, there were no statistically significant interaction between this allele and BMD in the distal radius, nor biochemical markers in patients with GD in remission. CONCLUSIONS: The present results do not support an association between the ERbeta microsatellite marker and AITD in the Japanese population. We also suggest that the ERbeta microsatellite polymorphism has at most a minor pathogenic importance in predicting the risk of osteoporosis as a complication of GD.

Journal Article↗
PubMed2000

Usefulness of ultrasonography in the management of nodular thyroid disease.

BACKGROUND: Fine-needle aspiration biopsy is the standard diagnostic test for evaluating possible malignancy in a thyroid nodule. OBJECTIVE: To evaluate the role of routine ultrasonography in the management of nodular thyroid disease. DESIGN: Retrospective chart review. SETTING: Multidisciplinary thyroid nodule clinic (endocrinology and radiology). PATIENTS: Patients with suspected nodular thyroid disease or suspected recurrent thyroid cancer referred between October 1995 and March 1997. All patients had thyroid ultrasonography and ultrasonography-guided fine-needle aspiration biopsy of nodules at least 1 cm in maximum diameter. MEASUREMENTS: Medical records, ultrasonography findings, cytology reports, and histologic reports were reviewed. Ultrasonography findings were compared with the referring physician's findings on physical examination. RESULTS: 223 patients were seen in the clinic. A total of 209 fine-needle aspiration biopsies were performed on 156 patients. Among 50 of 114 patients referred for a solitary nodule, ultrasonography detected additional nonpalpable nodules at least 1 cm in diameter in 27 and determined that no nodules required aspiration in 23. Of 59 patients referred for a diffuse goiter or a multinodular gland, ultrasonography detected discrete nodules at least 1 cm in diameter that required aspiration in 39 and determined that aspiration was unnecessary in 20. CONCLUSIONS: Ultrasonography altered the clinical management for 63% of the patients (109 of 173) referred to the thyroid nodule clinic after abnormal results on thyroid physical examination.

Biopsy, Needle↗
PubMed1992

Benign thyroid diseases and the risk of death from breast cancer.

A survey of the causes of death among women with benign thyroid disease was conducted to assess the risk of breast cancer mortality in thyroid patients. The study population was all women diagnosed with one of several types of thyroid disease at the Massachusetts General Hospital Thyroid Clinic from 1925 to 1974. A population-based comparison group was matched to the Clinic patients for age and socioeconomic status, resulting in a total of 9,520 matched pairs. A search of the Massachusetts mortality records located death certificates for 10.9% (1,039) of the Thyroid Clinic patients and 10.5% (995) of the comparison women. Cancer was the cause of death in 21% (218) of the Thyroid Clinic patients and 24% (239) of the comparison women. Fewer patients than comparison women died from cancers of the digestive organs (30.2 vs. 45.5%), but more patients died from thyroid cancer (3.7 vs. 0%), lymphatic and hematopoietic cancers (11.5 vs. 4.2%), and cancers of other sites (8.3 vs. 3.8%). Breast cancer deaths accounted for 21.6% of cancer deaths in the patients and 22.2% of cancer deaths in the comparison women. When specific thyroid diagnoses were considered, the percent of all deaths due to breast cancer ranged from 1.9 to 5.6%, compared to 5.3% in the comparison women. Of the diagnostic groups studied, patients with Hashimoto's thyroiditis had the lowest percent of deaths due to breast cancer, while those with nontoxic nodular goiter had the highest.

Adult↗
PubMed1986

[Interleukin 2 production in patients with thyroid diseases].

Con A-induced production of interleukin 2 was studied in peripheral blood lymphocytes obtained from 15 normal subjects and 42 patients with different thyroid diseases. It was found that thyroid diseases are accompanied by changes in IL 2 production. The level of IL 2 production by T lymphocytes is determined by the functional status of thyroid glands, their anatomy, stages of the disease and mode of treatment.

Adolescent↗