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PubMed1981

Hashimoto's thyroiditis simulating cancer of the thyroid.

We reviewed a group of 30 patients with Hashimoto's thyroiditis who underwent thyroidectomies for suspicion of cancer. A prominent nodule was present in all of the patients; compression symptoms were present in 13 and pain in the thyroid in six. The nodule was cold on scan in 21 patients. Lack of responsiveness to suppressive therapy or nodule enlargement occurred in 18 patients. In addition to the nodule, operative findings included adherence to surrounding tissues in seven patients, lymphadenopathy in seven, increased vascularity in four, and extension to distant cervical structures in two. Pathologic findings in the nodule were similar to those in the rest of the gland; they consisted of lymphocytic infiltration, fibrosis, and variable follicular size. Examination of lymph nodes demonstrated lymphoid hyperplasia. We emphasize the similarities between chronic thyroiditis and carcinoma of the thyroid; the occasional coexistence of these two conditions stresses the need for newer methods in the differential diagnosis.

Adult↗
PubMed1987

The frequency of cold thyroid nodules and thyroid malignancies in patients from an iodine-deficient area.

An analysis of thyroid cancer morbidity was carried out in two adjacent areas of Sicily differing in iodine intake. A consecutive series of 911 patients with "cold" nodules from an iodine-deficient area (IDA) and 2537 from a control area (CA) were examined by fine needle aspiration and selected for surgery and pathologic examination. Malignancies were found in 27 of the patients (2.96%) from the IDA and in 139 patients (5.48%) from the CA. Based on a population survey indicating that "cold" thyroid nodules were 2.5 times more frequent in the IDA with respect to the CA, we calculated a prevalence of 127 thyroid cancers per 10(5) inhabitants in the IDA versus 93 in the CA (P less than 0.001). Moreover, follicular and anaplastic carcinomas were three times more frequent in the IDA than in the CA (75 versus 24 cases per 10(5) inhabitants, respectively). These studies indicate that iodine deficiency may be one factor in the development of certain thyroid malignancies in man.

Adenocarcinoma↗
PubMed2005

Overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) as a novel gene responsible for anaplastic thyroid carcinoma.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is one of the most fulminant human malignancies. However, the molecular carcinogenic mechanisms of ATC are understood poorly. Recently, the authors performed a cyclic DNA (cDNA) microarray analysis with 11 anaplastic thyroid carcinoma cell lines (ACLs) and discovered several novel responsible genes for ACLs and ATC. From the extended list, they focused on hypothetical and anonymous genes and investigated a novel gene, named the overexpressed in anaplastic thyroid carcinoma-1 (OEATC-1) gene. METHODS: To investigate the role of the OEATC-1 gene in ATC carcinogenesis, first, the expression levels of OEATC-1 in ACLs, in various types of carcinoma cell lines, and in normal human tissues were examined with reverse transcriptase-polymerase chain reaction analysis. To explore the effect of OEATC-1 in ATC development, a cell-growth assay was performed with KTA2 cells under OEATC-1 gene silencing using small-interfering RNA (siRNA). RESULTS: OEATC-1 was overexpressed significantly in ACLs and in other types of carcinoma cell lines with various expression levels. Conversely, in normal human tissues, OEATC-1 was expressed weakly in placenta, kidney, spleen, thymus, small intestine, and thyroid gland. To evaluate the effects of OEATC-1 on tumor cell growth, gene silencing was caused by transfecting the plasmid-generating siRNA effect to KTA2 cells. Consequently, the silencing of OEATC-1 significantly suppressed the cell growth compared with controls. CONCLUSIONS: The current results indicated that OEATC-1 may have some oncogenic or cell growth-promoting function in ACL. OEATC-1 is considered a novel responsible gene in ATC.

Carcinoma↗
PubMed2003

Follicular thyroid lesions coexisting with Hashimoto's thyroiditis: incidence and possible sources of diagnostic errors.

Our objectives were to study the types and incidence of thyroid follicular lesions coexisting with Hashimoto's thyroiditis (HT), the pitfalls in their cytodiagnosis, and the effect on management. All cases of HT diagnosed by fine-needle aspiration (FNA) and/or histology over a 7-yr period were retrospectively studied. HT coexisted with follicular adenoma (FA) in 6 cases, follicular variant of papillary carcinoma (FVPC) in 1 case, and goitrous nodule (GN) in 2 cases. The overall incidence rates of thyroid neoplasm and goitrous nodules coexistent with HT were 15% and 3.5%, respectively. A preoperative FNA diagnosis was available in 10 histologically proven cases of HT. A false-positive diagnosis of follicular neoplasm (FN) that led to unnecessary thyroidectomies was given in 3 cases. In 2 of these, the cytological diagnosis was HT with the possibility of coexisting FN, and in the third case, the cytological finding of HT was misinterpreted as FN. The main causes of these diagnostic pitfalls were the presence of hyperplastic follicular cells with nuclear pleomorphism, a paucity of lymphoid cells in burned-out HT, and lack of ones exposure. Nuclear pleomorphism was observed in none of the follicular adenomas. FNA diagnosed accurately the coexisting lesions in 6 cases; 3 FA, 1 FVPC, and 2 GN, but it did not sample HT. In one case, FNA diagnosed correctly both HT and the coexisting FA. Therefore, the presence of a coexistent neoplasm or goitrous nodule reduced the chances of sampling HT by 85.7%, with no false-negative results. Indeed, aspiration on and around the thyroid nodule helps in sampling HT. However, HT may dominate the smear and obscure neoplasia. This can be avoided if the procedure is performed by the pathologist and the aspiration is done on the nodule only. The overlapping cytological features of FN and HT were the main causes of false-positive results. This can be reduced by avoiding the diagnosis of FN in the presence of follicular-cell pleomorphism and/or moderate to excessive numbers of lymphoid cells, provided proper aspiration technique is maintained.

Adenoma↗
PubMed1980

H-2 gene products influence susceptibility of target thyroid gland to damage in experimental autoimmune thyroiditis.

The restriction of the pathogenesis of experimental autoimmune thyroiditis (EAT) by H-2 gene products was investigated. EAT was induced by injecting thyroglobulin extract plus adjuvant into F1 hybrid mice that had been implanted under the kidney capsules with thyroid glands originating from either the EAT-susceptible or -resistant parental strain mice. We found relative H-2 restriction of thyroid damage to those glands originating from the H-2 susceptible parental strain. H-2 restriction of damage at the level of the target thyroid gland implicates cytotoxic effector T lymphocytes as a pathogenic agent of EAT.

Animals↗
PubMed1993

Thyroid hormone up-regulates thyroid hormone receptor beta gene expression in rat cerebral hemisphere astrocyte cultures.

Oligonucleotide probes complementary to specific regions of three thyroid receptor cDNAs were used to study the effects of thyroid hormone on the expression of the mRNAs encoding two alpha (alpha 1 and alpha 2) and one beta-thyroid (beta 1) receptors isoforms in rat cerebral hemisphere astrocyte cultures. Both genes are expressed by type 1 astrocytes. The levels of the alpha 1-, alpha 2-, and beta 1-mRNAs did not significantly change between day 8 and day 22, in cultures grown in the absence of thyroid hormone. L-triiodothyronine (L-T3) treatment of the cultures increased the levels of beta 1-mRNAs by fivefold without changing either the levels of the alpha 1- and alpha 2-mRNAs or L-T3 binding capacity. The effect of L-T3 on beta 1-mRNAs was observed after 4 h of treatment and was independent of protein synthesis, suggesting that this effect is likely to be a direct one. Treatment of the cultures by cytosine arabinosine, a drug that kills dividing cells, specifically decreased level of the alpha 1- and alpha 2-mRNAs by 60% and 38%, respectively. Finally, by immunocytochemistry, we showed that the beta 1 receptor-immunoreactivity was either located in the perinuclear region and the cytoplasm or in the nuclei of astrocytes. Taken together with previous data obtained in neuronal cultures where no effect of L-T3 was observed on the levels of the beta 1-mRNAs, our findings indicate that the beta 1 gene is differentially regulated in neurons and astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Papillary carcinoma of the thyroid after postpartum thyroiditis.

Postpartum thyroiditis is a benign, often self-limited cause of thyroid dysfunction. This report describes the first case of papillary carcinoma arising in a woman with postpartum thyroid disease. Both clinicians and pathologists must keep a high index of suspicion in postpartum patients with persistent thyroid abnormalities, even when a previous biopsy may have disclosed benign disease.

Adult↗
PubMed1993

Ultimobranchial body nests in human fetal thyroid: an autopsy, histological, and immunohistochemical study in relation to solid cell nests and mucoepidermoid carcinoma of the thyroid.

The mid portion of the lateral thyroid lobes from 64 fetuses was systematically analysed for the presence of ultimobranchial body nests. The nests showed a prevalence of 1/24 (4.2 per cent) or 13/40 (32.5 per cent) depending on whether a single- or a multi-step sectioning method was employed, respectively, and showed anatomical, morphological, and histochemical features similar to those of ultimobranchial postnatal thyroid solid cell nests. Histochemical studies revealed the presence of mucosubstances in 73 per cent of the cases, calcitonin-immunoreactive cells in 36 per cent, and both carcinoembryonic antigen and high-molecular-weight cytokeratin-immunoreactive epidermoid cells in 85.7 per cent, respectively. These findings indicate that these markers, which are also expressed by solid cell nests of the thyroid, are of value for the detection and tracing of ultimobranchial tissue to earlier stages of development. The findings of this study support the hypothesis that mucoepidermoid carcinomas of the thyroid are of ultimobranchial tissue origin.

Animals↗
PubMed1998

Selective pituitary resistance to thyroid hormone produced by expression of a mutant thyroid hormone receptor beta gene in the pituitary gland of transgenic mice.

Resistance to thyroid hormone (RTH) has been subdivided into generalized resistance (GRTH) and pituitary resistance (PRTH) based on the clinical impression of absence or presence of thyrotoxicosis. However, due to lack of objective clinical and genetic criteria, the existence of PRTH as a distinct entity became controversial. To determine what the phenotype would be if RTH was confined to the pituitary, a transgenic mouse was developed in which expression of the mutant thyroid hormone receptor (TR) beta (G345R) was targeted to the pituitary thyrotrophs by placing it downstream of the mouse thyrotropin beta promoter. This construct exhibited an antagonistic effect on the thyroid hormone-dependent transactivation, mediated through the wild-type TRbeta1, only when cotransfected with the thyrotroph embryonic factor in a heterologous cell line. As expected the transgene was transcribed predominantly in the pituitary gland but not in liver. These mice showed a significant, though modest, increase in serum T4 concentration. A decrease in the serum cholesterol was observed in keeping with the selective tissue hyposensitivity to thyroid hormone.

Animals↗
PubMed1998

The kinetics of cytokine gene expression in the thyroids of mice developing granulomatous experimental autoimmune thyroiditis.

To study the potential roles of cytokines in development and resolution of granulomatous experimental autoimmune thyroiditis (EAT), the kinetics of in vivo expression of cytokine genes in thyroid infiltrates was analysed using reverse transcriptase-PCR (RT-PCR). Both Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-10) cytokines as well as TGF-betaTNF-alphaIL-12 and IL-1beta were detected in thyroids during both the initial phase and peak of granulomatous EAT. Maximal expression of cytokine genes generally occurred 11-14 days after cell transfer, prior to maximal EAT severity, which occurred 19-21 days after cell transfer. The relative ratios of Th1:Th2 cytokines and mouse thyroglobulin-(MTg)-specific IgG1 and IgG2a autoantibody levels were similar during both the initial phase and peak of EAT. Depletion of CD8(+) T cells did not decrease the severity of EAT but delayed resolution of lesions. Cytokine gene expression in thyroids was not decreased by anti-CD8 treatment. Together, these data indicate that both Th1 and Th2 cytokines produced by CD4(+) T cells are involved in induction and development of granulomatous EAT, and CD8-dependent resolution of granulomatous EAT is apparently not mediated by these cytokines.

Animals↗
PubMed1998

Detection of a new de novo mutation at codon 251 of exon 8 of thyroid hormone receptor beta gene in an Italian kindred with resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) is almost invariably associated with mutations of the thyroid hormone (TH) receptor beta (hTR beta) gene and is inherited as an autosomal dominant disease. Mutations of hTR beta identified in patients affected by RTH cluster generally at two spots of the ligand binding domain. We investigated whether an Italian kindred with RTH had a mutation in the thyroid hormone (TH) receptor beta gene. Blood samples were obtained from the available family members for biochemical and genetic analyses. Thyroid function tests in basal conditions, and in the case of the propositus also following incremental doses of T3, were performed. Exon 4 to 10 of hTR beta gene were amplified using the polymerase chain reaction (PCR) and the mutation was identified by direct sequence analysis. The affinity constant of this mutated receptor for T3 was measured by in vitro transcription-translation and was then compared with that of wild type. We identified a heterozygous G to A transition at nucleotide 1037 of exon 8 at codon 251, resulting in a glycine (G) to glutamic acid (E) substitution (G251E) in the patient affected by RTH and in his affected offspring, but not in the normal family members. This novel mutation represents a de novo mutation since both parents of the index case were unaffected and did not have this genomic mutation. When expressed in vitro, the mutant protein (G251E) showed a marked decrease of the affinity for T3, suggesting an impaired ligand-dependent transactivation activity of this mutant receptor. In vivo studies with incremental doses of L-T3 demonstrated a reduced sensitivity to TH in the index case, in particular at the pituitary level where the thyrotrophs' activity was not completely inhibited even by 200 micrograms/day of L-T3. G251E mutation represents the fourth mutation described up to now in exon 8 of hTR beta among the subjects affected by RTH. A third cluster of mutations of the c-erbA beta gene located proximally with respect to the other two so far described begins to emerge in RTH patients.

Adult↗
PubMed1994

Mycobacterium avium intracellulare suppurative thyroiditis in a patient with Hashimoto's thyroiditis.

A case of suppurative thyroiditis occurring in a 72-year-old woman is reported. The clinical history of this woman, treated by tianeptine for mild exogenous affective disorder and by conventional insulin therapy for long-standing insulin-dependent diabetes, was remarkable for the pseudotumoral signs which led to the simultaneous diagnosis of hypothyroidism due to Hashimoto's thyroiditis and of mycobacterium avium intracellulare suppurative thyroiditis. To our knowledge, this is the second reported case of mycobacterium avium intracellulare thyroiditis. This case is also exemplary, given its occurrence in the absence of severe immunodepression, setting apart the mild impact on the immune system of affective disorder and of long duration's insulin-dependent diabetes.

Aged↗
PubMed1994

Lymphoma of the thyroid mimicking thyroiditis in a patient with the acquired immune deficiency syndrome.

A 35-year-old man with AIDS and a history of a remission from the lymphoma of the right tonsil (previously treated with chemotherapy and radiation) presented with a variety of clinical, laboratory and radiological findings strongly suggestive of subacute thyroiditis. Fine needle aspiration biopsy failed to establish the tissue diagnosis. Pathological examination of the thyroid tissue obtained during an open surgical biopsy revealed a lymphoma. Appropriate chemotherapy produced a rapid clinical and laboratory improvement manifested by the reduction of the goiter and restoration of a euthyroid state. Hypothyroidism subsequently developed, but therapy with thyroid hormone resulted in a rapid normalization of thyroid function tests. The patient expired because of AIDS-related complications.

Adult↗
PubMed1995

Simple radioimmunological assay of anti-alpha-galactosyl antibody (anti-Gal): application to autoimmune thyroid diseases and thyroid-associated ophthalmopathy.

Two radioimmunological techniques for the measurement of anti-alpha-galactosyl (anti-Gal) antibodies were developed and we demonstrated that this antibody is present in the serum of most untreated patients with Graves' disease, thyroid-associated ophthalmopathy (TAO) and autoimmune thyroiditis. Thyrotropin-binding inhibiting immunoglobulins (TBII) and Thyroid Stimulating Antibodies (TSAb) are frequently found in serum of patients with Graves' disease but not with autoimmune thyroiditis. Although TBII and anti-Gal were found sometimes simultaneously in the same serum samples, we demonstrated that anti-Gal could be present in the absence of TBII and reciprocally.

Animals↗
PubMed2000

[Insular carcinoma of the thyroid: a differentiated thyroid carcinoma with poor prognosis].

Insular carcinoma of the thyroid is a low differentiated type constituting about 5% of all thyroid cancers. Higher aggressiveness has been suggested as an important clinical feature. The value of preoperative fine-needle aspiration biopsy is not clearly proven for insular carcinoma. The criteria for histological diagnosis have been outlined by Carcangiu et al. Because of its aggressiveness, radical treatment at primary surgery appears advisable. Its clear distinction from undifferentiated (anaplastic) and medullary (C cell) cancers is important, as thyroglobulin is regularly synthesized by cancer cells. Enrichment of radioactive iodine makes such treatment feasible postoperatively and at relapse. Follow-up should be performed as in highly differentiated papillary and follicular thyroid cancer. A patient series of eight cases is presented. While all cancers were advanced at the initial diagnosis, the observed disease courses were in agreement with the assumption that insular carcinoma is a more aggressive form of differentiated thyroid cancer.

Adult↗
PubMed2000

Growth regulation of thyroid and thyroid tumors in humans.

In a study of growth regulation of the human thyroid gland and thyroid tumors we investigated the impact of iodine and that of the thyroid-specific growth-stimulating hormone TSH. Further studies included locally active growth factors such as the epidermal growth factor, insulin-like growth factor, and tissue transforming growth factors alpha and beta. In addition to studies of growth regulation by the various growth factors in mostly normal thyrocytes, the impact of tumor-specific mutations in oncogenes and tumor-suppressor genes was investigated. The results demonstrated distinct changes in tissue specificity and sensitivity to external stimuli. This rather complex view on thyrocyte growth regulation may be confusing, but it describes the biologic reality more precisely. Increased knowledge of the regulatory processes may lead to the development of new tumor- and patient-specific therapeutic approaches, especially for preventing benign goiter recurrence and for treating follicular and papillary thyroid cancers.

Genes, Tumor Suppressor↗
PubMed2001

Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited.

The effect of chronic lymphocytic thyroiditis (CLT) on the behavior of papillary thyroid cancer (PTC) remains unclear. In recent studies the presence of CLT in patients with PTC was reported to be associated with a lower recurrence rate and an improved survival rate. Furthermore, patients with PTC and tumor infiltrating lymphocytes (TILs) have been reported to have lower recurrence rates and a lower frequency of distant metastases. Because of these and other observations, a tumor immune response in PTC has been suggested. The aim of our study was to determine: (1) the relative frequency of CLT in PTC; (2) the prognostic significance of CLT in patients with PTC; and (3) if TIL occurs independently or in association with CLT. A 10-year retrospective study of patients who underwent initial thyroidectomy for PTC from 1986 to 1996 was completed. The extent of thyroid lymphocytic infiltration was determined within the tumor, surrounding the tumor, and in the distant parenchyma by two independent observers blinded to the clinical data. Dense focal/diffuse lymphoid aggregates throughout the thyroid gland were diagnostic of CLT and when present within or surrounding the tumor were designated TILs. A total of 136 patients with PTC (typical and follicular variant of PTC histologic subtypes) were identified with a mean follow-up of 4.4 years and a 8% mortality rate at 10 years. Thirty percent of the patients with PTC had coexisting CLT, and 65% of these patients with CLT had positive anti-thyroglobulin antibodies. Patients with coexisting CLT and PTC were younger (p < 0.05), more likely to be female (p < 0.05), and more likely to have multicentric tumors (p < 0.001) compared to patients without CLT. Only 5% of patients had TILs without CLT, but 82.5% of patients with CLT had TILs identified (p < 0.0001). By univariate analysis CLT, age, gender, stage of PTC, tumor multicentricity, and tumor size were significant prognostic factors. Only age and TNM stage of PTC remained independent prognostic factors by multivariate analysis. We found a similar frequency (30%) of coexisting CLT and PTC as reported by others; but, more importantly, the presence of TILs primarily occurred in association with CLT. The presence of CLT in patients with PTC correlated with an improved prognosis. It was not an independent prognostic factor, however, and was not associated with a lower recurrence rate or a lower frequency of distant metastasis.

Chronic Disease↗
PubMed1998

Thyroid dose and thyroid cancer incidence after the Chernobyl accident: assessments for the Zhytomyr region (Ukraine).

In the Zhytomyr region, about 52,000 measurements of the 131I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May-June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the 137Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed.

Adolescent↗