Contralateral Thyroid Lobe Research Articles

Thyroid papillary carcinoma: preliminary evidence for a germ-line single nucleotide polymorphism in the Fas gene.

The expression of Fas in thyroid tumours and Graves' disease was analysed by mRNA transcript expression. As compared with unaffected thyroid tissue, Fas expression was enhanced in Graves' disease, adenomas, and papillary and follicular carcinomas. This pattern was also reflected in immunohistochemical studies. The PCR single-strand conformational polymorphism (SSCP) method and DNA sequencing were used to analyse Fas exons 1-9. The study was carried out on five different histotypes of thyroid tumours (n=93) and tissue from Graves' disease patients. As compared with a group of healthy blood donors (n=64), a significant association (P=0.006) emerged between papillary thyroid carcinoma and a silent single nucleotide polymorphism (SNP, 988C-->T) in exon 7 of the Fas gene. Other forms of thyroid pathology were not associated with the above polymorphism. Patients with neoplasia showed the same SNP in tumour tissue, in the unaffected contralateral thyroid lobe, and in peripheral blood cells. Thus, the 988C-->T polymorphism appeared to be of germ-line origin.

Familial Nonmedullary Thyroid Carcinoma Characterized by Multifocality and a High Recurrence Rate in a Large Study Population

First-degree relatives of persons with thyroid cancer are known to be at relatively high risk for the disease. To better understand the clinicopathologic characteristics of familial nonmedullary thyroid carcinoma (FNMTC), we carried out a retrospective study in which we identified individuals treated at our institution who had at least one first-degree relative with the disease. We used data obtained from our patient records to compare the features of 258 cases of the disease with the features of sporadic papillary or follicular thyroid carcinoma in another group of patients. The 258 patients represented 154 families and were selected from among 6458 patients with papillary or follicular thyroid carcinoma who underwent thyroidectomy between 1946 and 2000. Compared to the patients with sporadic disease, the FNMTC patients were more likely to have intraglandular dissemination (28.5% vs. 40.7%; p < 0.0001) and multiple benign nodules (29.8% vs. 41.5%; p <0.0001). There were no significant differences between the two types of patients in terms of gender, age, tumor diameter, adhesion to or invasion of the surrounding tissues, macroscopic metastasis observed at surgery, histology, presence of single benign nodules, presence of chronic thyroiditis, microscopic metastasis, or rate of lymph node metastasis. Recurrence was statistically frequent in the FNMTC patients compared with that in the sporadic disease patients (16.3% vs. 9.6%; p = 0.0005), and the disease-free survival rate was significantly poorer in the FNMTC patients (p = 0.0041 by the Wilcoxon test and p <0.0001 by the log-rank test). No significant difference in the overall survival rate was found between the two groups. Multivariate analysis by Cox's proportional hazards method showed FNMTC to be an independent predictor of shorter disease-free survival (risk ratio 1.88; confidence interval 1.35-2.54; p = 0.0003). Locoregional recurrence in the ipsilateral or contralateral lymph nodes and contralateral thyroid lobe was significantly more frequent in the FNMTC patients than in the sporadic disease patients, whereas no difference was found regarding distant metastases. We conclude that FNMTC is a clinically distinct entity with an aggressive nature. Because of the frequent presence of benign nodules, multifocality, and high rate of locoregional recurrence, total or near-total thyroidectomy with modified radical neck dissection in FNMTC patients is recommended.

Benign nonfunctioning thyroid adenomas are characterized by a defective targeting to cell membrane or a reduced expression of the sodium iodide symporter protein.

Nodular thyroid disease is the most common endocrine disorder. Nonfunctioning thyroid nodules are identified by their low radioiodide uptake compared with the normal extranodular tissue, which, at thyroid scintiscan, produces the typical picture of a cold thyroid nodule. Previous in vitro studies demonstrated that the majority of nonfunctioning thyroid nodules have a specific defect in iodide transport that accounts for their failure to accumulate radioactive iodide in vivo. A defect in the expression or structure of the sodium iodide symporter (NIS) gene has been hypothesized as a possible cause of the impaired iodide trapping in nonfunctioning thyroid nodules. We studied 22 patients who were submitted to surgery for a solitary nonfunctioning thyroid nodule that originated in an otherwise normal gland. Thyroid scintigraphy was performed at 1, 2, 3, 4, 6, and 24 h after the oral administration of a tracer dose of 131I (iodine). All patients showed absence of 131I uptake in the nodule, with normal uptake in the extranodular tissue and in the contralateral thyroid lobe. Eight patients with toxic adenomas who underwent lobectomy were also included in the study. We first studied the expression of human NIS (hNIS) protein by immunohistochemistry in paraffin-embedded tissue sections using a specific anti-hNIS monoclonal antibody. Subsequently, we searched for somatic mutations of hNIS gene in nonfunctioning thyroid nodules. The level of hNIS expression was determined in both the nodules and the normal tissue from the same thyroid gland. In all functioning thyroid nodules (toxic adenomas), a high expression of hNIS protein was detected with respect to normal surrounding tissue. Similar to the normal thyroid tissue, follicular cells of toxic thyroid adenomas showed an exclusive expression of hNIS protein at the cell membrane. Fifty-four percent of benign nonfunctioning thyroid nodules overexpressed hNIS protein compared with the normal surrounding tissue, but in these nodules the hNIS protein failed to target the cell membrane, being mostly localized inside the cytoplasm. hNIS protein was not detected by immunohistochemistry in 46% of nonfunctioning nodules, whereas it was expressed in the surrounding unaffected thyroid tissue. Direct sequencing of the hNIS gene in all of the nonfunctioning nodules did not reveal major genetic alterations. A silent polymorphism (GCC/GCG codon 544, exon 13) was found in one nodule. In conclusion, the results obtained in this study show that two mechanisms contribute to the reduced radioiodide uptake typical of benign nonfunctioning thyroid nodules: 1) reduced expression of the hNIS protein, and 2) defective targeting of hNIS to the cell membrane.

Bilateral Thyroid and Ultimobranchial Medullary Carcinoma.

The ultimobranchial bodies in human embryos develop from the fourth and fifth branchial pouch complexes along with thymic and parathyroid tissue. They become incorporated within the lateral thyroid lobes and are believed to be involved in the development of C-cells. We report a case of an unusual bilateral thyroid and neck prelaryngeal medullary carcinoma in a 23-year-old male patient who belongs to a multiple endocrine neoplasia type 2a (MEN type 2a) family with thyroid tumors and pheochromocytomas. The medullary carcinoma was located in an abnormal cystic structure that seems to be a remnant of the ultimobranchial body (UBB) in the neck. Within the contralateral thyroid lobe, the medullary carcinoma was associated with C-cell hyperplasia.

Solid cell nests of the thyroid in medullary thyroid carcinoma.

Solid cell nests of the thyroid gland were studied in 44 patients with medullary thyroid carcinoma. In 10 (22.7%) patients, solid cell nests were revealed in the vicinity of tumour foci (five cases) or in the contralateral thyroid lobe and isthmus (four cases); in one case the location was indeterminate. In all seven cases in which immunohistochemical studies were carried out, solid cell nests showed negative staining for thyroglobulin, calcitonin and chromogranin A, findings which were distinct from those in medullary thyroid carcinoma. It is therefore suggested that solid cell nests of the thyroid are not precursors of this tumour.

Retrovirus-mediated gene transfer into canine thyroid using an ex vivo strategy.

We describe studies in a canine model aimed at establishing methods for ex vivo gene delivery to thyroid follicular cells. Canine follicular cells were harvested from tissue obtained by unilateral lobectomy, grown in thyrotropin-containing media, and transduced with amphotropic retroviral vectors carrying Escherichia coli beta-galactosidase or Tn7 neomycin-resistance genes. Up to 30% of cells were transduced with retroviral vectors containing the neomycin resistance gene, and transduced cells could be selected with G418. Significantly, transduced and selected cells exhibited the morphology of thyroid follicular cells and continued to express thyroglobulin. To assess the viability of cultivated and transduced cells for transplantation, cells were stained with the vital fluorescent dye DiI, recovered by trypsinization, and transplanted into the contralateral thyroid lobe of autologous animals. Engraftment was demonstrated by fluorescence microscopy and identification of proviral sequences 7-10 days after transplantation. Proviral transcripts were evident using coupled reverse transcription and the polymerase chain reaction using total RNA from transplanted glands. Thyroid follicular cells may represent an attractive target for gene therapy due to their proliferative potential, their large protein synthetic and secretory capacity, and their susceptibility to regulation. The thyroid might be a target for therapy of congenital or acquired thyroid diseases as well as disorders requiring regulated expression of proteins in the circulation. This work demonstrates the feasibility of ex vivo gene delivery to thyroid follicular cells that may be used in future investigations.

Avoiding Reoperation for Indeterminate Thyroid Nodules Identified as Malignant After Surgery

Thyroid nodules that are indeterminate as carcinoma by needle biopsy before surgery and by study of frozen sections at the time of surgery are occasionally identified to be malignant in later studies. If only a lobectomy has been performed, the advisability of reoperation to remove the remaining thyroid tissue to facilitate radioactive iodine therapy may cause concern. To obviate this difficulty as well as to reduce the occurrence of nodules later in a preserved contralateral thyroid lobe and to provide additional thyroid tissue for study, contralateral subtotal or near total lobectomy has been performed for indeterminate thyroid nodules. The small remnant of remaining thyroid tissue can later be ablated by radioactive iodine if desired. Of 37 patients with indeterminate thyroid nodules, none required reoperation, although the diagnosis of carcinoma was established after surgery for eight patients, three of whom were treated with radioactive iodine.

Indications for bilateral neck dissection in well-differentiated carcinoma of the thyroid.

This paper analyses the results of sixty-eight patients with thyroid carcinoma in whom bilateral modified radical neck dissection was performed, and discusses the indications for bilateral modified radical neck dissection. High frequencies of bilateral jugular lymph node metastases were found in eleven patients with obviously widespread involvement of both thyroid lobes, 13 with cancer mainly located in the isthmus, 2 with clinically detectable bilateral or contralateral jugular chain lymph node metastases, and 10 with recurrent thyroid cancer. Bilateral modified radical neck dissection, therefore appears to be indicated for those conditions. On the other hand, lymph node metastases in the contralateral neck were histologically confirmed in 6 out of 27 patients (22 per cent), in whom papillary carcinoma was clinically confined to one lobe, and where there were no obviously enlarged lymph nodes in the contralateral neck. In those patients, the histological confirmation of the contralateral thyroid lobe involvements, and of the contralateral paratracheal lymph node metastasis, appears to be a valid indication for elective contralateral modified radical neck dissection.

Operative indications and surgical procedure in iodine-induced hyperthyroidism

Clinical course, indications for surgical treatment, and results of treatment in 8 female patients with iodine induced thyrotoxicosis (IIT) are reported. The diagnosis of IIT could be established in all patients by a) clinical hyperthyroidism, b) increased T3 and T4 serum concentrations, and c) previous iodine contamination. Sources of iodine were radiographic contrast agents for urography (n = 4), oral cholecystography (n = 3), intravenous cholangiography (n = 1), phlebography (n = 1), and cranial computer tomography (n = 1). The onset of hyperthyroidism occurred 1-8 weeks after iodine exposure. Indications for surgical treatment of IIT were: 1. autonomous nodular goiter (n = 6), and 2. iodine exacerbation of preexisting thyrotoxicosis in patients with Graves' disease (n = 2). Corresponding to the different pathogenesis of autonomous and immunogenetic goiter the following surgical treatment is recommended: Enucleation of solitary autonomous adenomas or unilateral lobectomy in case of large adenomas, subtotal bilateral lobectomy in toxic multinodular goiter or, preferentially, unilateral lobectomy combined with subtotal resection of the contralateral thyroid lobe; "Near-total" thyroidectomy in Graves' immunopathy.

Role of the sympathetic nervous system in the control of thyroid compensatory growth of normal and hypophysectomized rats.

Compensatory thyroid growth in rats subjected to unilateral thyroidectomy (Tx) and superior cervical ganglionectomy (SCGx) performed ipsilaterally to the remaining lobe was about 2-fold that of rats subjected hemiTx alone, when assessed 7-15 days after surgery. HemiTx depressed serum T4 levels by 33% and increased serum TSH by 80% in control rats. Unilateral SCGx, which did not affect circulating T4 or TSH by itself, prevented hemiTx-induced changes of hormone levels. After hypophysectomy (Hpx) thyroid involution ensued. The subsequent hemiTx of Hpx rats did not affect Hpx-induced thyroid regression 7 days later, but abolished it 15 days later. At this time a factorial analysis of variance revealed lack of significant interaction between Hpx and hemiTx thus suggesting that a similar thyroid growth ensues after hemiTx regardless of pituitary intactness. However, both serum T4 and TSH levels were very low in Hpx rats regardless of whether one or two thyroid lobes were present indicating that thyroid growth in the absence of pituitary was not accompanied by increased secretory activity. SCGx performed ipsilaterally to the remaining lobe blunted the growth of the lobe in Hpx hemiTx rats. Moreover, the denervated thyroid lobe regressed in Hpx rats to values significantly lower than those of Hpx rats having intact sympathetic nerves both in the presence or in the absence of a contralateral thyroid lobe. SCGx did not modify the very low serum TSH and T4 levels of Hpx rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Thyroid function after radiotherapy and laryngectomy for carcinoma of the larynx.

Total levels of thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured in 37 patients who had previously had carcinoma of the larynx treated by radiotherapy and total laryngectomy with thyroid lobectomy. Ten percent of the patients had clinical features of hypothyroidism and 30% had total T4 levels below the lower limit of normal. A further 40% had results in the low normal range. Forty-four percent of patients had raised TSH levels, 90% of these having low or low normal T4 levels. The histology of the thyroid gland was normal in all 37 patients. Attention should be given to preserving intact the vasculature of the contralateral thyroid lobe whenever it is necessary to remove the ipsilateral thyroid lobe during a laryngectomy. Proper postoperative assessment of thyroid gland function is desirable in all these patients to identify those at risk of hypothyroidism and to avoid unnecessary morbidity.