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PubMed1995

Correlation of thyroid histopathology with fine needle aspiration of thyroid nodules: the St. Agnes Hospital experience.

Fine needle aspiration (FNA) cytology results were compared with thyroid tissue pathology reports in 44 patients who underwent thyroidectomy. Benign (12) and malignant (10) thyroid cytology interpretations correlated with the final thyroid histopathology. Of 22 thyroid aspirate samples that were considered suspicious or indeterminate, 5 were malignant and 17 were benign. The data obtained support the efficacy of FNA in the evaluation of thyroid nodular disease.

Adenocarcinoma, Papillary↗
PubMed2000

3-Cloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a rat thyroid gland carcinogen, does not affect serum levels of TSH and thyroid hormones.

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a chlorine disinfection by-product in drinking water, causes follicular adenomas and carcinomas in thyroid glands of Wistar rats with an unknown mechanism. We evaluated effects of MX on blood thyroid stimulating hormone (TSH), thyroxine (T(4)), triiodothyronine (T(3)), prolactin (PRL) and growth hormone (GH) levels in male and female Wistar rats to assess their role in the tumorigenesis. The levels of TSH, PRL and GH in serum of male rats were not significantly affected by a single dose of 1, 10 or 60 mg/kg of MX administered by gavage 2 h before sampling. In repeated dose experiments MX was administered at dose levels of 1, 10 or 60 mg/kg of MX (40 mg/kg for females) in water by gavage daily for 1 or 3 weeks. Thyroid glands, adrenal glands and the liver were evaluated for morphological changes and cell proliferation activity after staining with proliferating cell nuclear antigen (PCNA). The dose of 60 mg/kg MX was toxic upon repeated administration. Nevertheless, MX did not affect blood TSH and T(4) levels at any time point in either sex. T(3) concentration increased transiently in males (by 37% after week 1) at the highest MX dose but not in females. MX did not change the weights of thyroid glands, their morphology and cell proliferation activity by the end of the week 3. MX did not affect blood PRL levels but decreased GH levels in males at all doses after the first week of MX treatment. The results indicate that MX does not alter blood TSH and thyroid hormone levels in rats, and imply that MX may not cause thyroid follicular cell tumors by TSH-mediated hormonal promotion.

Journal Article↗
PubMed1987

Macromolecular binding of the thyroid carcinogen 3-amino-1,2,4-triazole (amitrole) catalyzed by prostaglandin H synthase, lactoperoxidase and thyroid peroxidase.

3-Amino-1,2,4-triazole, a thyroid carcinogen and goitrogen, is negative in a wide variety of short-term mutagenicity assays. However, amitrole induces gene mutations and morphological transformation in Syrian hamster embryo fibroblasts, cells known to carry out the prostaglandin H synthase (PHS)-mediated peroxidative metabolism of other carcinogens. Therefore, we have investigated the peroxidase-mediated binding of [14C]amitrole to macromolecules in vitro. We report here the PHS- and lactoperoxidase-catalyzed binding of [14C]amitrole to protein and tRNA, as well as protein binding by rat and hog thyroid peroxidase. PHS was an order of magnitude more active than lactoperoxidase and two orders of magnitude more active than thyroid peroxidase. The low levels of binding observed with thyroid peroxidase could be explained by the rapid and potent inhibition of this enzyme by amitrole. Although the thyroid peroxidase-mediated binding of amitrole was quite low, it was not inhibitable by compounds that would be expected to be competing substrates in vivo (i.e. I-, monoiodotyrosine, diiodotyrosine). Neither catalase nor horseradish peroxidase catalyzed binding of [14C]amitrole. It was also observed that an interaction between amitrole and protein and/or nucleic acid resulted in the slow generation of hydrogen peroxide, which then served as a substrate to drive peroxidase-mediated binding of [14C]amitrole. These data suggest that PHS may be responsible for conversion of amitrole to a mutagenic intermediate in Syrian hamster embryo cells. Furthermore, the generation of reactive metabolites of amitrole by thyroid peroxidase and/or PHS may contribute to the complete carcinogenicity of this compound by adding a mutagenic response to its potent hormonal effects.

Amitrole↗
PubMed1992

Decreased collagen gene expression and absence of fibrosis in thyroid hormone-induced myocardial hypertrophy. Response of cardiac fibroblasts to thyroid hormone in vitro.

The regulatory effects of thyroid hormone on biosynthesis of myocardial proteins that originate from cardiac myocytes are well established. Little is known, however, of regulatory effects of thyroid hormone on interstitial proteins. In this study we examined the effects of thyroid hormone on collagen gene expression in thyroid hormone-induced myocardial hypertrophy and the response of cardiac fibroblasts to thyroid hormone in culture. Adult male Sprague-Dawley rats were treated intraperitoneally with L-thyroxin (10 micrograms/100 g body wt) for 2 hours or 1, 2, 3, 6, 12, or 14 days. Northern blot analysis of RNA from total ventricular tissue showed that after 2 hours of treatment, the abundance of mRNA for pro alpha 2(I) collagen decreased by 53% (p less than 0.05) and reached the lowest level (60% decrease, p less than 0.02) at day 1, remained diminished at day 3, and then gradually returned toward normal levels. After transient transfection of chimeric DNA containing collagen type I promoter-chloramphenicol acetyl transferase (CAT) gene into the thyroxin-treated cardiac fibroblasts, the level of CAT activity decreased significantly. Treatment of cardiac fibroblasts in culture (10 nM L-thyroxin) resulted in a 33% (p less than 0.005) decrease in the abundance of mRNA for pro alpha 2(I) collagen. The stability of the mRNA for pro alpha 2(I) collagen in cardiac fibroblasts, as measured by mRNA half-life, was slightly (16.6%) decreased by thyroid-hormone treatment. Collagen synthesis as shown by immunofluorescent staining of intracellular collagen in cultured fibroblasts and in frozen sections of myocardium was also diminished.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyltransferases↗
PubMed1997

Occupational and Environmental Determinants for Benign Thyroid Disease and Follicular Thyroid Cancer.

Occupational and environmental determinants of benign thyroid disease and follicular thyroid cancer were evaluated in a series of cases in 1977-1987. Of the cases initially diagnosed as follicular thyroid cancer, only 31 remained after a reclassification, whereas 44 were found to be benign thyroid disease. Both series were compared with 387 randomly selected population controls. Occupational solvent exposure was strongly associated with benign thyroid disease (odds ratio, OR, 2.8; 95% confidence interval, 95% CI, 0.9-9.0 for women and OR 18.9; 95% CI 2.2-161 for men). Eight of the nine men found to have benign disease had been exposed to solvents, and six of them to trichloroethylene. For both types of cases, a private well at the birth address increased the risk, OR 2.0; 95% CI 0.9-4.0 and OR 3.0; 95% CI 1.2-7.2, respectively, whereas the risk was lower for those living in coastal areas. Less fish and shellfish in the diet increased the risk for malignant thyroid disease only. Although based on small numbers, the study indicates etiologic roles of occupational and environmental factors for both conditions studied. The influences of occupation and diet differ, however, for the two outcomes.

Journal Article↗
PubMed2006

Thyroid papillary carcinoma arising in ectopic thyroid tissue within a neck branchial cyst.

BACKGROUND: Thyroid gland derives from one median anlage at the base of the tongue, and from the two fourth branchial pouches. A number of anomalies may occur during their migration. These can be in form of ectopic tissues, which are frequently found along the course of thyroglossal duct and rarely in other sites, many of these may develop same diseases as the thyroid gland. CASE PRESENTATION: A 36-years-old female presented with a 3 month history of left side neck mass. The mass disappeared following aspiration of brown colored fluid, which on cytological examination showed cells with nuclear irregularities that warranted the resection of the lesion. The histology demonstrated a thyroid papillary carcinoma arising within the branchial cyst. Thereafter, the patient underwent a total thyroidectomy with central lymph nodes dissection. Histology showed a multifocal papillary carcinoma with central lymph nodes metastases. Only four cases of primary thyroid carcinomas in neck branchial cyst have been described so far. CONCLUSION: In a lateral cystic neck mass, although rare, occurrence of ectopic thyroid tissue and presence of a papillary thyroid carcinoma should be kept in mind.

Journal Article↗
PubMedDate not supplied

Thyroglobulin increment after thyroid hormone withdrawal is a reliable indicator for the detection of significant remnants or metastases in patients with differentiated thyroid carcinoma.

Serum thyroglobulin (Tg) measurement has a pivotal role in the management of differentiated thyroid carcinoma (DTC). Serum Tg increment after thyroid hormone discontinuation seems to be a better predictor of tumor recurrence, however, minimal Tg increment may not be a specific marker. This study tries to evaluate the importance of different levels of Tg increment after thyroid hormone discontinuation. Fifty-five patients (46 females and 9 males with mean age of 41.40 yrs) with DTC, treated with total or subtotal thyroidectomy and radioiodine-131 ((131)I) were studied. Ninety-one per cent of the patients had papillary carcinoma. Serum Tg and thyroid stimulating hormone (TSH) were measured using high sensitive IRMA assays during thyroxine (T4) suppression and after discontinuation of T4 treatment. The mean time interval between Tg on T4 and off T4 was 110.29+/-53.43 days and less than 180 days in all patients. Serum Tg level was increased >or= 1 ng/ml in 25 patients after discontinuation of T4. Of these patients, 17 had metastatic disease or a detectable thyroid remnant. Of 16 patients with unchanged Tg (-1 or= 7 ng/ml had residual disease or metastases. If DeltaTg was unchanged or decreased, the negative predictive value was 83.3%. The sensitivity of WB(131)IS was 63.6% for the detection of thyroid remnant or metastases. Our study indicates that DeltaTg is a more reliable indicator of remnant disease than on T4-Tg or off T4-Tg levels.

Journal Article↗
PubMed1990

Thyroid autoimmunity and thyroid autonomy.

While it is well established that autoimmune factors are the cause of goiter and hyperthyroidism in Graves' disease, these factors are not yet considered relevant in the development of thyroid autonomy. While an increased overall frequency of anti-Tg and anti-TPO antibodies has been found in moderate iodine-deficient areas, where thyroid autonomy is more frequently observed, there was evidence indicating that thyroid autoimmune phenomena were the consequence rather than the cause of the goiter. Thyroid Stimulating Antibodies (TSAb) have been reported in sera of patients with nodular autonomous goiter, but their pathogenetic relevance is uncertain, since these findings could not be confirmed by others. In our experience TSAb were detected in few cases with multinodular nontoxic goiter and were always associated with anti-TG and anti TPO antibodies, indicating that these patients have the nodular variant of Graves' disease. Besides TSAb, Thyroid Growth Stimulating Antibodies (TGAb) have been detected by different techniques in several goitrous conditions, including Graves' disease and sporadic or endemic nontoxic goiter. The precise nature of TGAb remains to be clarified, and particularly the relationship between TGAb and TSAb is still a matter of controversy. However, data indicating that TGAb cannot be dissociated from TSAb in Graves' sera suggest that these antibodies can be regarded as a sufficient pathogenetic agent for the development of both goiter and thyroid hyperfunction in Graves' disease. The relevance of TGAb in euthyroid goitrous conditions is uncertain, since conflicting results have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1989

[Diminution of thyroid stimulating hormone level but normal levels of thyroid hormones. Demonstration of occult hyperthyroidism].

The finding of a low basal concentration of thyroid-stimulating hormone (TSH) in the absence of high thyroid hormone levels is difficult to understand. In order to elucidate the meaning of such a dissociation, 22 patients without history of thyroid disease and showing clinical signs compatible with thyrotoxicosis were explored by the thyrotrophin-releasing hormone (TRH) test, by thyroid radioisotope scanning and, in case of high nodular uptake, by the triiodothyronine suppression test. A specific surgical, isotopic or medical treatment was instituted in the 17 patients who had a high nodular uptake unsupressible by triiodothyronine. During a clinicobiological re-evaluation carried out 6 months later, a significant clinical improvement was observed in 8 patients, and 12 patients whose free thyroxine level had decreased showed normal TSH levels. These results underline the value of thyroid radioisotope scanning in patients with isolated diminution of TSH. They confirm the reality of occult hyperthyroidism with normal thyroid hormone levels by the benefits observed after specific treatment.

Aged↗
PubMed1989

Short-term efficacy of thyroid hormone supplementation for patients with Down syndrome and low-borderline thyroid function.

The thyroid function of 44 subjects with Down syndrome who were between 2 and 51 years of age was assessed. Three patients (7%) had hypothyroidism, and in 2 of them high titers of antimicrosomal antibody were detected. Seven additional subjects (16%) had low-borderline thyroid function, 6 with elevated thyroid stimulating hormone. These 7 subjects constituted the cohort for an evaluation of the short-term benefits of thyroid hormone supplementation in the low-borderline thyroid functional state. A double-blind crossover drug placebo trial failed to document any cognitive, social, response time, or physical changes attributable to the 8- to 14-week drug treatment period compared to an untreated matched control group. Results provided no evidence for the efficacy of short-term thyroid hormone therapy for this population.

Adolescent↗
PubMed1985

The aging thyroid. Thyroid deficiency in the Framingham Study.

In an unselected population of elderly (over age 60 years) men and women (the original cohort of the Framingham Study), the prevalence of thyroid deficiency, evidenced by a clearly elevated serum thyrotropin (TSH) level (greater than 10 microU/mL), was 4.4%. Women had thyroid deficiency (5.9%) more often than men (2.3%). Of those with clearly elevated serum TSH levels, only 39% had low serum thyroxine (T4) levels; the remainder had serum T4 levels in the lower half of the normal range. Others (5.9%) had a slightly elevated serum TSH level (5 to 10 microU/mL); their status was not clear, but more (12.7%) had low T4 levels than expected. The level of serum T4 was not a sensitive measure of thyroid deficiency nor was routine examination by a physician, even when the patient's background contained a clue to a possible thyroid problem. An elevated serum TSH level was a sensitive marker of thyroid deficiency in the elderly and was often the only way to detect it. Further studies are needed to determine the relationship of thyroid deficiency to cognitive and cardiovascular function in older persons.

Aged↗
PubMed2000

American Thyroid Association guidelines for detection of thyroid dysfunction.

OBJECTIVE: To define the optimal approach to identify patients with thyroid dysfunction. PARTICIPANTS: The 8-member Standards of Care Committee of the American Thyroid Association prepared a draft, which was reviewed by the association's 780 members, 50 of whom responded with suggested revisions. EVIDENCE: Relevant published studies were identified through MEDLINE and the association membership's personal resources. CONSENSUS PROCESS: Consensus was reached at group meetings. The first draft was prepared by a single author (P.W.L.) after group discussion. Suggested revisions were incorporated after consideration by the committee. CONCLUSIONS: The American Thyroid Association recommends that adults be screened for thyroid dysfunction by measurement of the serum thyrotropin concentration, beginning at age 35 years and every 5 years thereafter. The indication for screening is particularly compelling in women, but it can also be justified in men as a relatively cost-effective measure in the context of the periodic health examination. Individuals with symptoms and signs potentially attributable to thyroid dysfunction and those with risk factors for its development may require more frequent serum thyrotropin testing.

Adult↗
PubMed1986

Thyroid suppression and medical ablation for differentiated thyroid cancer.

Patients with thyroid cancer benefit from treatment with exogenous thyroid hormone for two reasons: it provides adequate levels of thyroid hormone to peripheral tissues, and it reduces the level of thyrotropin, which may be an important growth factor in patients with differentiated malignant neoplasms. The use of radioactive iodine for thyroid cancer is highly controversial. Its most appropriate applications are in follicular cancers, in older patients, and in distant functioning metastases. Its value in papillary cancer is questionable, particularly in young patients. There is a great need for effective basic and clinical research on the natural course of differentiated thyroid cancer and the effects of specific therapies.

Adenocarcinoma↗
PubMed1998

Acute suppurative thyroiditis and aggressive malignant thyroid tumors: differences in clinical presentation.

BACKGROUND AND OBJECTIVES: Aggressive malignant thyroid tumors (AMTT) may mimic the clinical symptoms and signs of acute suppurative thyroiditis (AST) in the early course of the disease process. Our objective was to analyze the clinical features of these two conditions, to assess the best way of early diagnosis, and to propose proper treatment. METHODS: We retrospectively reviewed and analyzed the clinical features of 30 patients, who had similar clinical pictures of AST and were managed at Chang Gung Memorial Medical Center in Linkou, Taiwan, during the period from 1983 to 1996. These patients were consequently diagnosed as either AST or AMTT. The data were analyzed by the Mann-Whitney U, chi-square and Fisher's exact tests. RESULTS: Among the 30 patients, 25 patients (Male/Female (M/F) ratio = 9/16) were diagnosed as having AST and 5 (M/F ratio = 1/4) as AMTT. After statistical analysis we concluded that the presence of the following factors, namely, older age at diagnosis (P = 0.0155), history of dysphonia (P = 0.0325), right thyroid lobe involvement (P = 0.0151), large size of lesions (P = 0.0013), presence of anemia (P = 0.0075), and sterile pus cultures from thyroid aspirates (P = 0.0013) were cause to suspect a malignancy if the condition did not improve after antibiotics. Delay in diagnosis and management of AMTT may result in a poor prognosis (P = 0.0082). CONCLUSION: Due to the high mortality rate of AMTT, we should closely observe the patients with poor prognostic variables of acute thyroiditis. Earlier detection and aggressive surgical intervention for AMTT might improve the outcome.

Acute Disease↗
PubMed1999

Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture.

The inflammatory-mechanistic basis of subacute thyroiditis remains unclear. To elucidate the roles of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) in the inflammatory process, their immunoexpression was examined in biopsy specimens of ten cases. At the granulomatous stage, all cases expressed VEGF, bFGF, PDGF, and TGF-beta1 in monocytes/macrophages infiltrating into follicle lumina, and in both epithelioid histiocytes and multinucleated giant cells of the granulomas. In fibroblasts and endothelial cells around the granulomas, all cases displayed VEGF, bFGF, and PDGF, but TGF-beta1 was detected only in fibroblasts in two cases. No cases expressed EGF in any of the above cell types. At the regenerative stage, all cases expressed VEGF, bFGF, and EGF in regenerating thyrocytes, whereas three and no cases displayed PDGF and TGF-beta1, respectively. Ten, seven and six cases expressed PDGF in fibroblasts, endothelial cells, and monocytes, respectively. In these cell types, all cases expressed VEGF and bFGF, whereas no cases displayed TGF-beta1 and EGF. To estimate the roles of these growth factors in thyroid tissue regeneration, their effects on thyroid folliculogenesis and angiogenesis were examined using collagen gel culture of thyrocytes and endothelial cells, respectively. Cell proliferation was also studied by bromodeoxyuridine (BrdU) uptake. EGF decreased follicle formation and TGF-beta1 drastically inhibited it, but the others had no effect. VEGF showed the greatest effect on vessel formation, although all of the others promoted it. EGF and VEGF or bFGF caused the highest BrdU uptake in thyrocytes and endothelial cells, respectively. The data suggest firstly, that at the granulomatous stage of subacute thyroiditis, growth factor-rich monocytes/macrophages infiltrating into follicle lumina trigger the granulomatous reaction, and VEGF, bFGF, PDGF, and TGF-beta1 produced by the stromal cell types tested mediate the reaction; secondly, that at the regenerative stage, EGF serves follicle regeneration through its mitogenic effect on thyrocytes, although some cofactors with EGF are involved in folliculogenesis and the decreased expression of TGF-beta1, a fibrogenic factor, contributes to thyroid tissue repair; and thirdly, that VEGF and bFGF are more responsible for the angiogenesis at both stages than the other factors studied.

Cell Culture Techniques↗
PubMed1985

Pyruvate kinase in normal human thyroid tissue and thyroid neoplasms.

Pyruvate kinase (ATP: pyruvate-2-O-phosphotransferase, EC 2.7.1.40) was studied in human thyroid carcinomas (n = 9), follicular adenomas (n = 32), and normal thyroid tissue (n = 12). The specific activity in carcinomas (mean 0.94 +/- 0.44) is significantly increased (P less than 0.0001) in comparison with pyruvate kinase in normal tissue (mean, 0.14 +/- 0.05). Specific activities of follicular adenomas are rather heterogeneous. When these tumors were divided into three groups of increasing proliferative activity as judged by histopathologic criteria, highest specific activities of pyruvate kinase were found in the group with the highest proliferative activity. On the other hand, specific enzyme activities of the least active tissues (colloid-containing follicular adenomas) were comparable to normal. The isoenzyme composition of normal thyroid tissue is characterized by the presence of K4, K3M, and K2M2 types of pyruvate kinase. In carcinomas, mainly K4 and K3M are found. Undifferentiated tumors express more K4 type compared with follicular and papillary carcinomas. Follicular adenomas with high specific activity show the same electrophoretic pattern as found in follicular carcinomas. Pyruvate kinase from malignant tumors is more inhibited by the amino acid L-alanine than the enzyme from normal thyroid tissue as a consequence of the presence of more K subunits in the malignant tissues. The K4 type from normal thyroid tissue is not kinetically different from the K4 type of carcinomas.

Adenoma↗