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[Treatment guidelines for inflammatory and malignant diseases of the thyroid gland].

Most cases of thyroiditis can be treated with antibiotics, antiphlogistics, and corticosteroids. In case of abscess caused by bacterial infection or compression of the trachea surgical therapy is required for drainage and resection. The prognosis for differentiated malignant tumours of the thyroid gland is good even if metastases have occurred. The recommended therapy includes total resection of the thyroid gland and radioiodine therapy to eliminate any remaining thyroid tissue. For anaplastic thyroid carcinomas surgery should be considered because of the extremely poor prognosis for these types of tumours. Resection should be performed to improve the patient's quality of life by avoiding tracheostoma or to ensure normal nutritional uptake. Medullary thyroid carcinoma is known in sporadic and in hereditary forms. Thyroidectomy is the accepted therapy. In 15% of the patients we observed the syndrome of multiple endocrine neoplasms (MEN), which is a form of thyroid carcinoma complicated by pheochromocytoma and hyperparathyroidism. Diagnosis of thyroid carcinomas includes examination of the patient, scintigraphy and ultrasonography of the thyroid gland, and cytological examination by aspiration biopsy. Post-operative care includes substitution of thyroid hormones, regular measurement of the thyreoglobulin levels in the blood, and examination for metastases in the lungs, the abdomen, and the bones.

Aftercare↗

The effect of gadolinium contrast media on radioiodine uptake by the thyroid gland.

OBJECTIVE: Patients with thyroid cancer may require detailed anatomic imaging before 131I therapy. Imaging by contrast-enhanced CT is contraindicated because it may result in saturation of tissues with iodine, decreasing the avidity of thyroid or thyroid cancer cells to subsequent radioiodine for extended intervals. Gadolinium-enhanced MRI offers an alternative to CT for detailed anatomic imaging. However, it is not known whether gadolinium contrast affects uptake of iodine by the thyroid gland since lanthanides affect ion transport in a variety of ways. The objective of this project was to determine whether the gadolinium MRI contrast injection alters thyroid uptake of radioiodine. METHODS: Radioiodine uptake by the thyroid gland was measured at 6 h and 24 h after the oral administration of 100 microCi 123I-Na-I. Three to seven days later, a standard dose (20 mL) of Magnevist (gadolinium DTPA) was administered intravenously. Another capsule of 100 microCi 123I Na-I immediately was given orally, and 6-h and 24-h radioiodine uptake by the thyroid gland was again measured and compared to baseline values. RESULTS: There was no statistically significant difference in uptake of radioiodine uptake by the thyroid gland between baseline values and those acquired immediately after the administration of Magnevist. CONCLUSION: Contrast-enhanced MRI may be safely performed before contemplated determinations of thyroid uptake of radioiodine, 131I therapy for hyperthyroidism, and postsurgical 131I imaging and therapy for well-differentiated thyroid cancer.

Adult↗

[Expression of galectin-3 in thyroid gland and follicular cell tumors of the thyroid. A critical study of its possible role in preoperative differential diagnosis].

Galectin-3 belongs to a group of endogenous lectins with an affinity to glycoconjugates containing beta-galactoside residues. It has been detected in numerous tissues and studied in connection with tumor growth, dedifferentiation, and metastasis. Only few studies have dealt with galectin-3 detection in tumors of the thyroid gland and with its possible role for differential diagnosis. We studied 118 cases of thyroid gland tumors with a monoclonal antibody against galectin-3; we compared the preparations by a semiquantitative score to determine differences in expression. Normal thyroid gland tissue, goiter tissue, and tissue with functional enhancement were largely negative for galectin-3. Adenomas with a typical cytological pattern were predominantly negative, but a focal positive reaction in single cells and cell groups or follicles was possible. Almost all papillary carcinomas showed a distinct galectin-3 expression. While findings in follicular carcinomas and oxyphilic adenomas and carcinomas were very uneven, with both positive and negative tumors, the galectin-3 reaction can be helpful in recognizing follicular variants of the papillary carcinoma. Investigation of the biological significance of tumors should always be cautious and consider known histological criteria for malignancy.

Adenocarcinoma, Follicular↗

Alpha-1-antichymotrypsin immunoreactivity in papillary carcinoma of the thyroid gland.

AIM: Papillary thyroid carcinoma (PTC) is the most common malignant tumour of the thyroid gland. The immunohistochemical profile of PTC is characterized by immunoreactivity of tumour cells for cytokeratins, thyroglobulin, vimentin, EMA and S100 protein. Recently, the presence of a serum protease inhibitor, alpha-1-antitrypsin (A1AT), has been demonstrated in tumour cells of PTC. The aim of our study was to test immunoreactivity of PTC for another inhibitor of proteases, alpha-1-antichymotrypsin (A1ACT). METHODS AND RESULTS: Serial paraffin sections of nine consecutive cases of PTC were tested with anti-A1AT and anti-A1ACT antibodies. No immunoreactivity for A1AT and A1ACT was found in the normal thyroid tissue surrounding each tumour. In seven out of nine cases, tumour cells of PTC showed cytoplasmic immunoreactivity for A1ACT. In two cases, A1ACT was detected even in the nuclei. Immunoreactivity for A1AT was found only in three cases. Two cases of PTC showed no staining for both A1ACT and A1AT. No significant correlation of A1ACT staining was found with various prognostic indices (age of patients, histological pattern, tumour size, presence of regional lymph node metastases). The two cases showing a lack of staining for both A1ACT and A1AT showed a more aggressive clinical behaviour. CONCLUSIONS: Our preliminary study shows that A1ACT is expressed by tumour cells in a large proportion of papillary carcinomas of the thyroid gland. Its significance remains, to the best of our knowledge, still unknown. The observation of a more aggressive behaviour in the two cases characterized by the absence of immunoreactivity for both A1ACT and A1AT suggests that the presence or absence of protease inhibitors could play a role in controlling tumour progression in PTC.

Adolescent↗

Regulation of the phosphatidylinositol 3-kinase, Akt/protein kinase B, FRAP/mammalian target of rapamycin, and ribosomal S6 kinase 1 signaling pathways by thyroid-stimulating hormone (TSH) and stimulating type TSH receptor antibodies in the thyroid gland.

Thyroid-stimulating hormone (TSH) regulates the growth and differentiation of thyrocytes by activating the TSH receptor (TSHR). This study investigated the roles of the phosphatidylinositol 3-kinase (PI3K), PDK1, FRAP/mammalian target of rapamycin, and ribosomal S6 kinase 1 (S6K1) signaling mechanism by which TSH and the stimulating type TSHR antibodies regulate thyrocyte proliferation and the follicle activities in vitro and in vivo. The TSHR immunoprecipitates exhibited PI3K activity, which was higher in the cells treated with either TSH or 8-bromo-cAMP. TSH and cAMP increased the tyrosine phosphorylation of TSHR and the association between TSHR and the p85alpha regulatory subunit of PI3K. TSH induced a redistribution of PDK1 from the cytoplasm to the plasma membrane in the cells in a PI3K- and protein kinase A-dependent manner. TSH induced the PDK1-dependent phosphorylation of S6K1 but did not induce Akt/protein kinase B phosphorylation. The TSH-induced S6K1 phosphorylation was inhibited by a dominant negative p85alpha regulatory subunit or by the PI3K inhibitors wortmannin and LY294002. Rapamycin inhibited the phosphorylation of S6K1 in the cells treated with either TSH or 8-bromo-cAMP. The stimulating type TSHR antibodies from patients with Graves disease also induced S6K1 activation, whereas the blocking type TSHR antibodies from patients with primary myxedema inhibited TSH- but not the insulin-induced phosphorylation of S6K1. In addition, rapamycin treatment in vivo inhibited the TSH-stimulated thyroid follicle hyperplasia and follicle activity. These findings suggest an interaction between TSHR and PI3K, which is stimulated by TSH and cAMP and might involve the downstream S6K1 but not Akt/protein kinase B. This pathway may play a role in the TSH/stimulating type TSH receptor antibody-mediated thyrocyte proliferation in vitro and in the response to TSH in vivo.

8-Bromo Cyclic Adenosine Monophosphate↗

Evidence that both long-acting thyroid stimulator and long-acting thyroid stimulator-protector stimulate the human thyroid gland.

Thyroid-stimulating immunoglobulins were prepared from two potent sera, one contained long-acting thyroid stimulator (LATS) and the other contained both LATS and LATS-protector (LATS-P). The potencies of the immunoglobulin G (IgG) preparations were estimated in the McKenzie assay. The accumulation of cyclic AMP in mouse thyroid lobes was stimulated only by LATS--IgG; LATS-P--IgG was inactive. In contrast, both LATS-IgG and LATS-P--IgG were equally effective in slices of human thyroid.

Animals↗

Immunohistochemical detection of thyroid transcription factor-1, thyroglobulin, and calcitonin in canine normal, hyperplastic, and neoplastic thyroid gland.

Immunohistochemistry for thyroid transcription factor-1 (TTF-1), thyroglobulin, and calcitonin was done in normal, hyperplastic, and neoplastic canine thyroid glands that had been fixed in formalin and embedded in paraffin. Prolonged fixation did not significantly alter the immunostaining for TTF-1. Staining for TTF-1 was always nuclear and usually strong. One of two C-cell adenomas, five of five follicular cell adenomas, 5 of 11 C-cell carcinomas, 38 of 42 follicular cell carcinomas, two of five cases of C-cell hyperplasia, two of two cases of follicular epithelial hyperplasia, one of two metastatic C-cell carcinomas, and three of four metastatic follicular carcinomas were positive for TTF-1. One follicular carcinoma that was positive for TTF-1 was negative for thyroglobulin. Thirty-nine of 42 follicular cell carcinomas were positive for thyroglobulin, including two cases that were negative for TTF-1. All C-cell lesions were positive for calcitonin. Of a variety of normal canine tissues and 278 nonthyroid tumors, only normal lung (airway and alveolar epithelial cells) and four of five pulmonary carcinomas were positive for TTF-1. TTF-1 is a good marker of thyroid differentiation and can be used in conjunction with thyroglobulin and calcitonin to increase the detection and differentiation of thyroid tumors and their metastases.

Adenoma↗

[Total thyroidectomy in C-cell hyperplasia of the thyroid gland].

INTRODUCTION: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor of the thyroid parafollicular or C-cells. MTC accounts for approximately 3 to 5% of thyroid carcinomas. A characteristic feature of this tumor is production of calcitonin. Sporadic MTC accounts for 60-80% of all cases of the disease. The most common presentation of sporadic MTC is a solitary thyroid nodule, which occurs in 75 to 95% of patients. It typically occurs in the fifth or sixth decades, with slight female predominance. CASE REPORT: A case of a 58-year old woman with elevated basal calcitonin levels (221 pg/ml) has been presented. Preoperative ultrasound of the thyroid gland and body (99m)Tc DMSA scintigraphy showed a diffuse goiter. Hyperparathyroidism and pheochromocytoma were not present. Total thyroidectomy was performed. Only C-cell hyperplasia was found. DISCUSSION AND CONCLUSION: Many patients with elevated basal serum calcitonin level ranging between 150 and 1000 pg/ml, have only C-cell hyperplasia, but a few have small MTCs. For persons in known kindreds with familial MTC, prospective screening, using serum calcitonin measurement, can identify those at risk for the disease before MTC is clinically evident. Due to the possibility that any patient with MTC may have multiple endocrine neoplasia type 2 (MEN-2), preoperative testing must also include measurement of serum calcium (to rule out hyperparathyroidism) and a test for pheochromocytoma. Total thyroidectomy is indicated in patients with high levels of calcitonin.

Calcitonin↗

Pituitary enlargement secondary to hypothyroidism associated with sublingual thyroid gland.

Two patients with sublingual thyroid glands and hypothyroidism since childhood are described. Because of enlargement of the sella turcica both were erroneously diagnosed as having primary pituitary tumors resulting in secondary hypothyroidism. One of the patients was even treated with pituitary gland irradiation. Following substitution thyroid therapy, thyroid-stimulating hormone (TSH) levels promptly returned to normal. Ectopic thyroid glands, which are often incapable of adequate hormonogenesis, may cause secondary pituitary enlargement and lead to the suspicion of a pituitary adenoma. The correct diagnosis can easily be established by measuring serum TSH levels, which are elevated in the former condition.

Adult↗

Ultrastructural changes in thyroid epithelium during involution of the hyperplastic thyroid gland.

The ultrastructure of the thyroid epithelial cell was examined at various time intervals after induction of involution of the hyperplastic thyroid gland. Thyroids were made hyperplastic by the feeding of thiouracil in a Remington low-iodine diet to male Fischer rats for 3 weeks. Involution was induced by replacing the thiouracil-containing diet with Purina Laboratory Chow, a high-iodine diet. During involution, organelles that play a role in the synthesis and secretion of thyroglobulin, such as the rough endoplasmic reticulum, Golgi apparatus, and apical vesicles, were well preserved and prominent features of the epithelial cell. The apical plasma membrane of many cells was highly irregular for approximately 2 weeks with signs suggesting rapid discharge of apical-vesical contents into the lumen of the follicle. Pseudopods and colloid droplets were present but were not very prominent features of the cell. No signs of extensive autophagy or obvious increased incidence of lysosomes were present, although there was an elevation in the incidence of small dense bodies starting about day 8, and prominent by 15 days. Some of these may be phagosomes formed from luminal debris. The observations indicate that involution of the hyperplastic thyroid in which there is maintenance of the protein synthetic apparatus and little sign of autophagy or death of the epithelial cells is remarkably different from phenomena occurring during involution of prostate or mammary glands.

Animals↗