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[Punctate cytology of benign and malignant changes in the thyroid gland (author's transl)].

80 thyroid gland aspirates obtained post-operatively were compared with 69 clinically punctured cases. The results suggest that the vast majority of cytological misdiagnoses are caused by a faulty withdrawal technique. As a contribution to the differential diagnosis of "follicular neoplasia" an attempt was made to introduce the diameter of the nucelus obtained morphometrically as a parameter of malignancy. In aspirates of highly differentiated follicular carcinomas a significantly higher percentage of thyrocytes with larger nuclear diameters are found than in benign nodular changes in the thyroid gland.

Adenocarcinoma↗

Therapeutic implications of prognostic factors in differentiated carcinoma of the thyroid gland.

Differentiated thyroid carcinoma is a relatively indolent disease. Despite the usually favorable prognosis, differentiated thyroid cancer is fatal in some patients. In the past, treatment strategies were often based upon incomplete knowledge or inaccurate assumptions regarding the significance of the presenting characteristics of the tumor and patient. More recently, several large retrospective reviews have analyzed various presenting factors and have identified those that have prognostic significance and those that do not. Significant prognostic factors are age, primary tumor size, histology, grade, local tumor extension, and M stage. N stage appears to be a significant factor in older patients but not in younger patients. Gender, focality, and a history of prior irradiation are not significant prognostic factors. Using this knowledge, patients can be grouped into low, intermediate, and high risk groups. Prognostic factor and risk group analysis has facilitated the development of more rational treatment algorithms. Low risk patients can usually be treated with lobectomy and suppression therapy. For high risk patients, total thyroidectomy and adjuvant radioiodine is advocated. Treatment for patients in the intermediate risk group should be individualized. Prognostic factor and risk group analysis makes a selective approach to differentiated thyroid cancer possible. Such an approach can spare many patients the morbidity and expense of unnecessarily aggressive treatment without compromising outcome.

Adult↗

[Trans-sternal cervico-mediastinal primary tumor resection and lymphadenectomy in thyroid gland cancer].

Thyroid carcinoma may invade the mediastinum by direct extension of the primary tumor or metastases to the paratracheal or retroclavicular-parajugular lymph nodes. From 1975 to 1991 in 47 out of 622 thyroid cancer patients (7.6%) [14 papillary (PTC), 5 follicular (FTC), 16 medullary (MTC) and 12 undifferentiated carcinoma (UTC)] transsternal tumor resection has been performed. Four patients (UTC three, MTC one) deceased 7, 8, 35, and 41 days after resection of the primary tumor due to cardiac or tumor disease, and in one patient because of acute arteriotracheal haemorrhage after external irradiation; no patient deceased after transsternal resection as a result of cervicomediastinal lymphadenectomy. At the time of primary operation 80% of patients showed an advanced tumor stage (greater than pT3). In 34% of patients (PTC 64%, FTC 40%, MTC 13%, UTC 25%) no tumor recurrence was observed neither by imaging nor by biochemical methods. In 18 patients a transsternal microdissection of all four cervicomediastinal lymph node compartments has been performed. Histological analyses of excised and tumor involved lymph nodes revealed in 9 patients unilateral cervical and mediastinal and in 9 patients bilateral cervical and mediastinal lymph node metastases. In the case of unilateral cervicomediastinal lymph node metastases 2 out of 2 patients with papillary and 2 out of 6 patients with medullary thyroid carcinoma could be cured surgically. In the case of bilateral cervicomediastinal lymph node metastases 3 out of 4 patients with papillary thyroid carcinoma, but no other thyroid cancer patient were free of disease. In conclusion, main indications for transsternal cervicomediastinal resection in thyroid carcinoma are (1) primary tumors extending to the upper mediastinum, but without lymph node metastases, and (2) thyroid carcinomas with unilateral cervicomediastinal lymph node metastases. In the case of bilateral cervicomediastinal lymph node metastases probable only papillary thyroid carcinomas are supposed to be curable by transsternal multicompartmentectomy.

Adenocarcinoma↗

Medullary carcinoma of the thyroid gland.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid tumor that has attracted a great deal of interest because of its frequent presentation as a familial tumor and its primary involvement in the type II multiple endocrine neoplasia (MEN) syndromes MEN-IIA and MEN-IIB and familial medullary thyroid carcinoma (FMTC). The MTC tumor cells secrete the polypeptide hormone calcitonin, which serves as an excellent tumor marker, useful for defining the presence of disease, preoperatively or following thyroidectomy. The discovery that mutations in the RET proto-oncogene are associated with MEN-II syndromes was highly significant in that it demonstrated a clear correlation between genotype and phenotype; and most importantly it provided a mechanism whereby family members at risk could be identified by direct DNA analysis. Virtually all patients with MEN-IIA, MEN-IIB, and FMTC develop MTC; therefore there is a clear rationale for performing thyroidectomy as soon as a RET mutation has been identified. Because MTC appears to be much more aggressive in patients with MEN-IIB, thyroidectomy is performed during the first year of life in this setting, whereas in patients with MEN-IIA, where the tumor appears to be more indolent, the procedure can be safety delayed until age 5 years. Reoperative neck exploration in patients with evidence of persistent or recurrent MTC has been effective in a significant number of patients, although the success of the operation requires careful patient selection and preoperative assessment. MTC, as expressed in the MEN-II syndromes, is an excellent model to evaluate the usefulness of interventional therapy in patients demonstrated to have a genetic predisposition for cancer.

Carcinoma, Medullary↗

Primary leiomyoma of the thyroid gland.

Primary thyroid leiomyomas are rare, and only four cases have been reported to date. This is a report of an additional case of primary thyroid leiomyoma in a 40-year-old male who was admitted with a painless swelling in the right thyroid lobe and underwent subtotal thyroidectomy. The surgical specimen showed a well-circumscribed, greyish-white solid nodule. Histologically, the tumour was composed of spindle cells with blunt-ended nuclei that were arranged with short intersecting bundles. Immunohistochemical staining revealed reactivity with smooth muscle actin, vimentin and desmin. Histopathologic and immunohistochemical assessments produced the diagnosis of thyroid leiomyoma. Although primary thyroid leiomyoma is rare, it should be considered in the differential diagnosis of a cold thyroid nodule.

Adult↗

[Follicular carcinoma of the thyroid gland].

Follicular thyroid cancer is the second most common thyroid malignancy. This tumor has a predisposition for hematogenous dissemination an extra thyroid spread. Accurate cytological diagnosis of follicular thyroid cancer is not possible and this fact highlights the necessity for surgical treatment of any suspicious thyroid nodule. Aggressiveness of this tumor is greater than in the case of papillary thyroid cancer and it is the reason for radical surgical treatment of follicular thyroid cancer. Total thyroidectomy facilitates later adjuvant therapy with thyroid hormones and radioiodine. This procedure improves the outcome and the risk of relapse. Results of our study clearly demonstrate that diagnosis of follicular thyroid cancer in us is established in the early phase of the disease (78.57%), but the significant number of the patients (21.43%) is still in the advanced phase of the disease.

Adenocarcinoma, Follicular↗

[Papillary carcinoma of the thyroid gland].

Papillary thyroid cancer is after ovarian cancer the most frequent malignant disease of the endocrine system and because of this fact, early detection and appropriate surgical treatment is essential. Radical surgical treatment lower the risk of the disease relapse and postoperative adjuvant therapy with radioiodine is possible as well as postoperative follow up with thyreoglobulin measurement. If the total thyroidectomy is performed in highly specialized institution the risk of postoperative complications is acceptable and therefore is the treatment of choice for papillary thyroid cancer. Only the patients with occult papillary thyroid cancer can be treated with hemithyroidectomy. In our series of 410 patients the majority of the patients (85.12%) were in the early phase of the disease and the degree of successfully performed radical surgery for papillary thyroid cancer was very high (tumor reduction was performed in only 1.46% of cases).

Adolescent↗

Grey scale ultrasonography of the thyroid gland, Nigeria.

Thyroid ultrasonography was performed on a combined series of 108 patients over a four-year period. Ultrasonography enabled superb visualisation of the neck, specifically the thyroid, and discriminated solitary from diffuse thyroid abnormalities and segregated these into cystic, solid or 'complex' patterns. Sonographic-pathological correlation was obtained in 38 cases, consisting of 14 follicular adenomas, 11 goitres, 3 Hashimoto thyroiditis, 6 colloid cysts and 4 carcinomata; the clinical course confirmed 11 cases of Graves' disease for a total of 49 confirmed cases. The sonographic patterns lack histological specificity; however, a pattern recognition approach can be developed to better select patients for surgery. Such an approach appears suitable in tropical Africa, where radionuclide imaging may not be available. Diagnostic ultrasound is affordable, versatile and efficacious and without any known biological risks. A plea is made for its increased availability.

Adenocarcinoma↗

TRH testing, T4-thyrotoxicosis and the aging thyroid gland.

Secondary thyroid function tests were compared in 41 mildly thyrotoxic and 36 euthyroid patients with an elevated free thyroxine index (FT4I). A serum TSH measurement 20 minutes after intravenous TRH (delta TSH) most reliably separates these two groups. A significant delta TSH response (greater than 0.5 microU/ml) is also helpful in excluding clinical thyrotoxicosis in patients with nodular goitre. The free T3 index was normal in one-third of mildly thyrotoxic patients and in all euthyroid patients with a falsely elevated FT4I. Blunted delta TSH responses to TRH in elderly New Zealand women were associated with nodular goitre or occult thyroid nodularity revealed only by thyroid scan. The reduced TRH responses are more likely due to partial thyroid autonomy than reduced synthetic capacity of thyrotrophs in old age.

Adolescent↗

[Follicular carcinoma with sarcomatoid dedifferentiation or thyroid gland carcinosarcoma?].

Thyroid carcinoma may at times display unusual clinical and anatomo-pathologic behaviour. The case of a female patient associating goiter of long standing with a fulminating terminal course is presented. Since the patient was never treated, the evolution of her condition is thought to reflect the natural biologic behaviour of the disease process. Pathologic examination revealed the co-existence of both follicular and anaplastic carcinoma within the primary lesion. Moreover, metastases were either entirely follicular or poorly differentiated in structure, and occasionally even of striking sarcomatoid appearance. The possibility of carcinosarcoma was entertained but dismissed in view of the recent literature. Rather, the hypothesis of tumour dedifferentiation offers a more satisfactory explanation for the clinical course and pathologic findings.

Aged↗

[Cardiopulmonary involvement in thyroid gland diseases].

Thyroid hormones exercise a direct influence on the lung and myocardium. It has been found that at the heart of patients suffering from hyperthyroidism there is an increased production of contractile proteins and a redistribution of myosin Isoenzymes. Reduced efficiency results from the increased oxygen consumption and insufficient adaptation of the heartbeat to stress. Thyroid hormones are responsible for reducing arterial resistance; a higher incidence of supraventricular arrhythmias has been observed. In contrast, the cardiac changes in hypothyroidism are associated with an enhanced deposition of glycosaminoglycan in the myocardium. Besides bradycardia and low voltage there is an increased incidence of pericardial, pleural and peritoneal effusions with high protein content. Patients suffering from hypothyroidism have a higher incidence of atherosclerotic changes. Hypothyroidism is associated with a reduction of the beta-adrenergic receptors, and hence disturbances of rhythm are rare and do not increase even under substitution therapy. Pulmonary involvement in hyperthyroidism is evident from an enhanced respiratory minute volume, a reduced vital capacity, and dyspnoea at rest. In patients suffering from hypothyroidism, hypoventilation reduces the efficiency. Over and above this, myopathic changes of the respiratory muscles have been described. Involvement of thyroid hormones in the maturing of type II pneumocytes and of the surfactant factor has also been under discussion.

Cardiovascular Diseases↗

[In vitro studies of the thyroid gland regulation principles and their evaluation].

The free fractions of the thyroid hormone further the metabolism of the body cells and regulate the synthesis of the thyroid hormone. Once the level of FT3 and FT4 decreases. With the help of a liberation of the hormone stimulating the thyroid gland from the anterior lobe of the pituitary gland the lack of thyroid hormone is corrected. The synthesis and secretion of the thyroid gland stimulating hormone is induced by the thyreotropin releasing hormone which is given by the hypothalamus. Moreover, the organism is able as needed to carry out the monodiodation of LT4 to biologically active LT3 or biologically inactive so-called revers T3 (RT3). The estimation of thyroid gland stimulating hormone before and 30 minutes after intravenous application of thyreotropin releasing hormone has its main importance for the early recognition of a disturbance of the regulating circle hypophysis-thyroid gland, above all in the diagnosis of clinically not yet manifest clinical pictures, such as the latent hypothyreosis and the latent hyperthyreosis, respectively (Basedow hyperthyreosis and thyroidal autonomy). According to the questioning the estimations of the levels of the thyroid hormones and of the thyroid gland stimulating hormone should be used stepwise.

Animals↗

Culture of dendritic cells from a nonlymphoid organ, the thyroid gland: evidence for TNFalpha-dependent phenotypic changes of thyroid-derived dendritic cells.

Because they are sparsely distributed in tissues, dendritic cells (DC) present in nonlymphoid organs are difficult to isolate. Only DC from skin and lung have been successfully studied in culture. The objective of the present work was to investigate the possibility of isolating and culturing DC from an endocrine organ, the thyroid gland, which is particularly susceptible to the development of autoimmune processes. The study was conducted on pig thyroid glands to have sufficient amounts of starting material. This choice required the characterization of immunological reagents capable of recognizing DC markers in the pig species. Using a discontinuous trypsinization procedure, a DC population representing 2% to 3% of the thyroid cell suspension was reproducibly obtained. Isolated DC quantitatively attached to tissue culture-treated dishes and segregated from thyrocytes. DC identified as cells expressing major histocompatibility complex class II molecules, the mannose receptor, and the S100 protein were found to have a high capacity to internalize labeled ligands, dextran, and mannosylated albumin. These cells had a phenotype of immature DC. Secondarily, a fraction of DC detached from culture dishes, and floating DC had low or no endocytic activity, a characteristic of mature DC. Treatment of DC/thyrocytes cocultures with tumor necrosis factor alpha (TNFalpha) activated the transformation of immature DC into mature DC. These data show that DC isolated from the thyroid gland can be maintained immature or activated to undergo maturation in primary culture. The procedure of cell isolation and culture should be adaptable to human thyroid tissue for in vitro analyses of DC-mediated immune responses.

Animals↗

Colon cancer metastatic to the lung and the thyroid gland.

The clinical diagnosis of primary thyroid cancer is uncommon, constituting 1.5% of all cancers in the United States. Clinically diagnosed metastatic cancer to the thyroid gland is rare. Colon cancer is one of the most common cancers in the United States, with a high propensity to metastasize; 30% to 40% of patients have metastatic disease at the initial diagnosis. The most common sites of metastasis from colon cancer are the regional lymph nodes, the liver, the lung, and the peritoneum. Colon cancer metastasis to the thyroid gland is rare, with only a few reported cases, mainly in the pathology literature. These cases describe metastasis from colon cancer to the thyroid gland that became apparent years after the initial diagnosis of colon cancer and were usually associated with dissemination to the liver, the lung, or both. We report a case of colonic adenocarcinoma metastatic to the thyroid gland and lung without involvement of the liver. A review of the literature is also included.

Adenocarcinoma↗

A mode of action for induction of thyroid gland tumors by Pyrethrins in the rat.

Prolonged treatment with high doses of Pyrethrins results in thyroid gland tumors in the rat. To elucidate the mode of action for tumor formation, the effect of Pyrethrins on rat thyroid gland, thyroid hormone levels and hepatic thyroxine UDPglucuronosyltransferase activity was investigated. Male Sprague-Dawley CD rats were fed diets containing 0 (control) and 8000 ppm Pyrethrins and female rats diets containing 0, 100, 3000 and 8000 ppm Pyrethrins for periods of 7, 14 and 42 days and for 42 days followed by 42 days of reversal. As a positive control, rats were also fed diets containing 1200-1558 ppm sodium Phenobarbital (NaPB) for 7 and 14 days. The treatment of male rats with 8000 ppm Pyrethrins, female rats with 3000 and 8000 ppm Pyrethrins and both sexes with NaPB resulted in increased thyroid gland weights, which were associated with follicular cell hypertrophy. Thyroid follicular cell replicative DNA synthesis was increased by treatment with Pyrethrins and NaPB for 7 and/or 14 days. Treatment with Pyrethrins and NaPB increased hepatic microsomal thyroxine UDPglucuronosyltransferase activity and serum thyroid stimulating hormone levels (TSH), but reduced serum levels of either thyroxine (T4) and/or triiodothyronine (T3). The effects of Pyrethrins in female rats were dose-dependent, with 100 ppm being a no-effect level, and on cessation of treatment were essentially reversible in both sexes. The concordance between the effects of Pyrethrins and NaPB suggests that the mode of action for Pyrethrins-induced rat thyroid gland tumors is similar to that of some other non-genotoxic inducers of hepatic xenobiotic metabolism.

Administration, Oral↗