Laura Sterian Ward

Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy

Aims : To investigate the usefulness of immunohistochemical expression and immunolocalization of a panel of thyroid malignancy markers including HBME‐1, cytokeratin (CK) 19 and galectin‐3.

Recommendations of the Latin American Thyroid Society on diagnosis and management of differentiated thyroid cancer.

The aims of these recommendations were to develop clinical guidelines for evaluation and management of patients with differentiated thyroid cancer applicable to Latin American countries. The panel was composed by 13 members of the Latin American Thyroid Society (LATS) involved with research and management of thyroid cancer from different medical centers in Latin America. The recommendations were produced on the basis of the expert opinion of the panel with use of principles of Evidence-Based Medicine. Following a group meeting, a first draft based on evidences and the expert opinions of the panel was elaborated and, later, circulated among panel members, for further revision. After, this document was submitted to the LATS members, for commentaries and considerations, and, finally, revised and refined by the authors. The final recommendations presented in this paper represent the state of the art on management of differentiated thyroid cancer applied to all Latin American countries.

Nódulos de tireóide e câncer diferenciado de tireóide: consenso brasileiro

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that ~10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5‐10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information. (Arq Bras Endocrinol Metab 2007;51/5:867-893)Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

Prevalence of papillary microcarcinoma of the thyroid in Brazilian autopsy and surgical series.

In order to search for parameters to differentiate patients at low and high risk for development of thyroid cancer, we studied thyroids from 166 consecutive autopsies and 261 thyroids that were surgically resected for thyroid diseases in general. We found 32 papillary microcarcinomas, corresponding to 7.8% of autopsies and 7.2% of surgical material, with a higher incidence between 30 and 49 yr of age. Both genders were similarly affected: 9.3% of the men and 8.8% of the women in autopsy series, and 6.2% of the men and 7.3% of the women in surgical series, suggesting that hormonal factors may favor the subsequent development of clinical lesions in women. Although associated nodular goiter has been observed in 54% of autopsies and 26% of surgical specimens, while Hashimotos thyroiditis only in surgical material (15% of the cases), we were not able to correlate risk of malignancy with any concomitant lesion. The smallest papillary microcarcinomas presented most frequently as nonencapsulated nonsclerosing tumors without inflammatory infiltrate or fibrosis, suggesting that they may represent the early stages of development. Our data show a relatively high and similar frequency of papillary microcarcinomas in surgical and autopsy series, but do not demonstrate risk factors for clinical evolution.

Impact of previous thyroid autoimmune diseases on prognosis of patients with well-differentiated thyroid cancer.

Autoimmune phenomena are frequently associated with differentiated thyroid carcinomas. However, the significance of thyroid gland autoimmune aggression on the outcome of these patients is still controversial. To address this issue, we studied 173 patients (123 with papillary and 50 with follicular carcinomas) who underwent surgery complemented by radioiodine ablation and followed up for 0.5-29 (6 +/- 5.76) years. Analysis of the prognostic factors revealed that higher age, male gender, larger nodule size, follicular tumors, presence of metastases at diagnosis, grade of differentiation, and stage correlated positively with the occurrence of death, metastasis and/or recurrence, while the presence of antibodies and the previous history of autoimmune disease correlated negatively with these events. Long distant metastases increased the odds for a lower disease-free rate for patients with papillary (8.366 times) and follicular (7.373 times) carcinoma. However, univariate and multivariate analysis failed to demonstrate that neck node involvement could influence the outcome for patients with well-differentiated thyroid carcinoma. The odds for patients with previous history of thyroid autoimmune disease (p < 0.02) or with thyroid autoantibodies (p < 0.001) to have a worse outcome were lower than for patients with no evidence of autoimmune activity, suggesting that autoimmune activity against the gland may exert a protective effect on the outcome of differentiated thyroid carcinoma patients.

Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma

Immune responses against differentiated thyroid carcinomas (DTC) have long been recognized. We aimed to investigate the role of immune cell infiltration in the progression of DTC.

Clinical and Pathological Implications of Concurrent Autoimmune Thyroid Disorders and Papillary Thyroid Cancer

Cooccurrences of chronic lymphocytic thyroiditis (CLT) and thyroid cancer (DTC) have been repeatedly reported. Both CLT and DTC, mainly papillary thyroid carcinoma (PTC), share some epidemiological and molecular features. In fact, thyroid lymphocytic inflammatory reaction has been observed in association with PTC at variable frequency, although the precise relationship between the two diseases is still debated. It also remains a matter of debate whether the association with a CLT or even an autoimmune disorder could influence the prognosis of PTC. A better understanding about clinical implications of autoimmunity in concurrent thyroid cancer could raise new insights of thyroid cancer immunotherapy. In addition, elucidating the molecular mechanisms involved in autoimmune disease and concurrent cancer allowed us to identify new therapeutic strategies against thyroid cancer. The objective of this article was to review recent literature on the association of these disorders and its potential significance.

Smoking and susceptibility to thyroid cancer: an inverse association with CYP1A1 allelic variants

In contrast to most human malignancies, epidemiologic studies have frequently reported a reduced risk of differentiated thyroid cancer in tobacco consumers. Cytochrome P4501A1 (CYP1A1) gene variants may be related to an increased capacity to activate polycyclic aromatic hydrocarbons, producing highly reactive electrophilic intermediates that might damage DNA. Hence, the germline inheritance of a wild-type CYP1A1 gene may decrease the susceptibility for thyroid cancer. The present study was designed to investigate CYP1A1 (m1 and m2) role in thyroid tumorigenesis and its connection with GSTM1, GSTT1, GSTP1, GSTO1, and codon 72 of p53 genotypes. A total of 248 patients with thyroid nodules, including 67 benign goiters, 13 follicular adenomas, 136 papillary carcinomas, and 32 follicular carcinomas, and 277 controls with similar ethnic backgrounds were interviewed on their lifetime dietary and occupational histories, smoking habit, previous diseases, and other anamnestic data. DNA was extracted from a blood sample and submitted to PCR-restriction fragment length polymorphism assays. The wild-type CYP1A1m1 genotype was more frequent among papillary carcinoma patients (74.26%) than in the control population (62.45%; P=0.0147), reducing the risk for this type of cancer (odds ratio=0.564; 95% confidence interval=0.357-0.894). A multiple logistic regression analysis showed an inverse correlation between cigarette smoking (P=0.0385) and CYP1A1 germline inheritance (P=0.0237) with the susceptibility to papillary carcinomas. We were not able to find any correlation between smoking, clinical features, parameters of aggressiveness at diagnosis or during follow-up, and any of the GST or CYP genotypes considered separately or in different combinations. We suggest that CYP1A1 genotype might be associated with the reported reduced risk to papillary carcinomas among smokers.

Low expression of sodium iodide symporter identifies aggressive thyroid tumors

A decreased radioiodine uptake is frequently detected in differentiated thyroid carcinomas (DTC) and is associated with high recurrence rate and reduced survival. We investigated the correlation between NIS mRNA expression levels in the primary tumor and patient outcome using a quantitative real-time RT-PCR method. NIS expression was decreased in 17 DTC (21.04+/-39.66 pg Eq) compared to four autoimmune thyroid disease (180.51+/-92.63 pg Eq) and 14 normal tissues (75.71+/-66.98 pg Eq) (p<0.0001). The 17 thyroid differentiated carcinoma patients were submitted to surgery complemented by radioiodine ablation and had at least 24 months of follow-up, under levothyroxine continued suppressive therapy. According to their outcome, we could characterize a group of papillary carcinoma patients with aggressive carcinomas, whose NIS mRNA levels were markedly lower than a group with non-aggressive carcinomas (0.62+/-0.79 versus 54.87+/-53.79; p<0.005). We suggest that the quantification of NIS mRNA relative levels in the primary tumor may predict poor outcome.

The difficult patient: drug interaction and the influence of concomitant diseases on the treatment of hypothyroidism

Although most hypothyroid patients do well with one single tablet of thyroxine daily, approximately 10% are dissatisfied and another important group of patients is difficult to control. We reviewed the most common causes for frequent-dose adjustment or high-dose requirement, including poor compliance with therapy and inadequate medication. Since these two causes have been ruled out, drug interaction and other concomitant diseases need to be investigated. Requirements of thyroxine increase in all conditions characterized by impaired gastric acid secretion. Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption. In addition, a series of diseases including celiac disease and chronic inflammatory intestinal diseases, as well as nutritional habits may be important in patient control. Finally, we mention the effects of a growing list of drugs and thyroid disruptors that may also affect thyroid hormone metabolism at many levels.