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Purpose: The occurrence and histopathological features of incidental thyroid carcinoma (ITC) vary considerably among populations from different geographical regions. The aim of this study is to assess the prevalence and histopathological characteristics of ITC in patients who underwent thyroid surgery for apparently benign thyroid diseases in an endemic goiter area in Italy., Methods: A total of 649 consecutive patients (531 females and 118 males; mean age, 52.9 ± 11.0 years), who underwent thyroid surgery at the Endocrine Surgery Unit of the tertiary care "Renato Dulbecco" University Hospital (Catanzaro, Italy) in the period between years 2017 and 2022, were included in this retrospective study. A comprehensive histopathological examination was performed on surgically excised thyroid tissue. Logistic regression analysis was employed to identify potential predictors of ITC., Results: The histopathological examination revealed the presence of ITC in 81 patients, accounting for 12.5% of the total study population. The female to male ratio was found to be 6.4 to 1. Among the patients with ITC, 72 had papillary carcinoma (PTC), with 53 of these tumors being microcarcinomas (microPTC). Additionally, 5 patients had follicular thyroid carcinoma, 2 patients had low-risk follicular cell-derived thyroid neoplasms, 1 patient had an oncocytic carcinoma, and 1 patient had a medullary thyroid carcinoma. Logistic regression analysis demonstrated a significant association between female sex and incidental microPTC., Conclusions: These findings provide further evidence of the common occurrence of ITC, typically in the form of microPTC, among individuals who undergo thyroid surgery for apparently benign thyroid diseases., (© 2024. The Author(s).)

Background: Nowadays, the Republic of Belarus belongs to the countries with sufficient iodine supply, which made it possible to reduce the incidence of non-toxic goiter and congenital hypothyroidism. However, even a slight change in iodine consumption influences the pattern of thyroid diseases. In addition to iodine deficiency, other environmental conditions, as well as genetic factors, play a significant role in the etiology of thyroid diseases., Aim: To analyze the dynamics of the main epidemiological indicators of benign thyroid diseases from 2009 to 2019 in the adult population of the Republic of Belarus, using the data of official state statistics., Materials and Methods: The indicators of the incidence and prevalence of benign thyroid diseases were studied on the basis of state statistics for 2009-2019. To analyze the dynamics of the studied indicators, regression analysis was used with the construction of linear and polynomial models., Results: A decrease in the incidence and prevalence of diffuse euthyroid goiter and an increase in the incidence and prevalence of nodular euthyroid goiter, thyroiditis, acquired hypothyroidism, Graves' disease, as well as the incidence of nodular toxic goiter were revealed., Conclusion: Obtained data indicate, that there is an increase in the prevalence of most of the studied thyroid diseases, despite the adequate iodine supply. The above justifies the need for further study of the causes of the identified trends, as well as the necessity of developing new methods of diagnosis and treatment of thyroid diseases.

Background: Various factors can affect incidence of thyroid disorders and disease profiles may show abrupt changes in endemic goitrous areas. In this study, it was aimed to analyze the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) and the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) in terms of risk of malignancy and general recommendations in an endemic goiter region (EGR)., Methods: In this retrospective study, a total of 500 patients who had thyroidectomy following thyroid fine needle aspiration biopsy were enrolled. For the assessment of thyroid cytology, BSRTC was used and for the evaluation of ultrasound features of thyroid nodules, ACR TIRADS lexicon was adopted. For the assessment of thyroid cytology, Bethesda classification was used and for the evaluation of ultrasound features of thyroid nodules, ACR TIRADS lexicon was adopted., Results: In the EGR setting, benign category of BSRTC had a cancer risk of 6.2% which was two times more than the 2017 BSRTC revision reported. Nodules 10-14.9 mm in diameter had nearly 4 times higher malignancy risk than nodules >15 mm. In this group of patients, the risk of malignancy for TIRADS level 1, 2, 3, 4 and 5 was 1.16%, 2.94%, 7%, 45.64% and 94.44%, respectively. The malignancy rates for Bethesda system category I, II, III, IV, V and VI were as follows: 14.43%, 6.2%, 19.05%, 36.73%, 75.68% and 100%., Conclusions: There are slight differences between the common set of standards and this study results regarding risk of malignancy. This brings up the question whether there is need for revision for the use of categories and the appropriate management in endemic goiter regions.

This study was conducted to investigate the natural history of undifferentiated thyroid carcinoma (UTC) in the iodine-deficient province of Salta, Argentina, in relation to salt iodization and health care standards. Five hundred ninety-three thyroid cancers diagnosed from 1958 to2012 were reviewed based mainly on the WHO classification and grouped into three periods, one before and two after iodine prophylaxis. The incidence of UTC was analyzed in relation to changing concentrations of potassium iodide (KI) in salt during the prophylaxis period (from 40 to 33.3 mg KI/kg salt), establishment of primary health care centers throughout the region, and use of fine needle aspiration (FNA) cytology. Twenty-nine UTCs were found in the whole series. The frequency of UTC decreased from 15.2 % (9/59 cases) in the first period to 2.6 % (10/381 cases) well after salt iodination (x (2) Fisher's test, p < 0.0002), and the incidence from 1.4/10(6)/year to 0.1/10(6)/year (Student's t test, p < 0.06), respectively. The decline of UTC after iodine prophylaxis occurred even after decreasing concentrations of KI in salt and timely coincided with the establishment of primary health care centers throughout the region and routine use of FNA. The lower rate of UTC after iodine prophylaxis in the province of Salta is mostly related to earlier detection of more differentiated thyroid tumors rather than higher salt iodization.

Objective: Stiffness has been associated to malignancy in prostate and breast, as well as thyroid. Ultrasound elastography objectively measures tissue elasticity, and previous studies have described it as a high sensitivity and specificity technique for the detection of malignant thyroid nodules in high-risk populations. The aim was to assess the accuracy of elastography in a population with low risk of malignancy., Design and Patients: 128 consecutive patients with nodular goiter were recruited. Elastography and ultrasound-guided fine-needle aspiration were performed. When malignancy was suspected by citology, surgery was recommended. Thyroid nodules were classified by elastography according the criteria described by Ueno, and an alternative classification. Sensitivity, specificity, predictive values, and odds ratio were calculated., Results: Most patients were female, aged 56.1 year, with single nodule (52.0%) or multinodular goiter (45.6%), and a few thyroiditis (2.4%). The majority of nodules were mostly elastic. Fine-needle aspiration found 86% of benign nodules, 9.3% of indeterminate, and 4.7% possibly malignant. After surgery, 3 malignant nodules were confirmed, all of them being papillary carcinomas. All the malignant nodules were mostly elastic, as well as 75% of indeterminate nodules. Low values of sensitivity and specificity were found for elastic nodules being benign and hard nodules malignant., Conclusion: In a low-risk population for thyroid cancer, elastography lacks accuracy for the diagnosis of malignant nodules., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Endemic goitre is a major concern in many parts of the world, including Southeast Asia. Goitrous thyroid lesion is postulated as a precursor lesion to thyroid cancer (TC). This paper reviews the prevalence rates and characteristics of TC among cases of goitrous thyroid-swelling in different parts of Malaysia and Myanmar. Recorded data from hospital-based retrospective studies of thyroid cases, whose study periods ranged from three to 11 years, were analysed. These included research findings from the author's publications as well as other published review articles of retrospective analyses. The incidence of TC varies among gender, age, race/ethnicity and histological type. There appears to be a higher rate of occurrence among females aged 21-60 years. Papillary thyroid carcinoma is the more common histological type compared to follicular cancer. This review also presents a descriptive analysis and discussion on studies conducted in other countries. Further exploration is warranted in order to uncover the possible risk factors for the rising incidence of TC.

The essentially desirable standardisation of various European and American guidelines for the evaluation of thyroid nodules has led to the recommendation to perform fine-needle biopsy (FNB) in all nodules >1 cm in order to detect clinically occult thyroid carcinoma early. However, in iodine-deficient areas such as Germany (where thyroid nodules are found in approximately 25% of the adult population) this recommendation would substantially increase both the number of FNB and thyroid operations without significantly increasing the cancer detection rate. The recommendation for FNB in Germany, therefore, should be restricted to hypofunctioning ("cold") nodules >1 cm.

Background: Thyroid malignancies are a heterogeneous group oftumours which show considerable variability in biological behaviour, histological appearances and response to therapy. Thyroid cancer is uncommon and represents only 1% of all malignancies. Objective was to determine the prevalence of malignancy in patients presenting with goitre. This prospective, observational study was conducted at Department of Surgery, Fauji Foundation Hospital, Rawalpindi from January 1999 to December 2008., Methods: All patients requiring surgery for goitre were included in the study. Postoperatively histopathologies of specimens were evaluated in all patients., Results: 718 patients were operated and post operative histopathology specimens were reviewed. 2.92% of patients were found to have malignancy. Prevalence of papillary and follicular carcinoma was 33.33% each. Anaplastic carcinoma was found in 23.81% of patients followed by Hurthle cell carcinoma in 9.53% of patients., Conclusion: All postoperative thyroid specimens should be subjected to histopathology. Prevalence of follicular carcinoma and anaplastic carcinoma is relatively higher in our country due to high incidence of iodine deficiency goitre.

We aimed to evaluate the incidence of thyroid cancer in Turkish patients with hyperthyroidism who had undergone thyroid surgery. The data of 344 patients who had been operated on for hyperthyroidism between 1998 and 2006 at our center were evaluated retrospectively. Sixty-five of the subjects had single toxic adenomas, 223 had toxic multinodular goiter, and 56 had Graves' disease. In 35 of 344 patients (10.1%), papillary carcinoma was diagnosed. Other forms of thyroid carcinomas were not observed. The rate of carcinoma was found to be 11.6% in patients with toxic multinodular goiter, 7.7% in patients with single toxic adenomas, and 7.1% in patients with Graves' disease. Occult papillary carcinoma was found in 62.9% of all malignancy diagnoses. The primary aim in the surgical treatment of hyperthyroidism should be to abolish the hyperthyroid state. However, the probability of malignancy, especially occult carcinoma, should always be considered.

Purpose: To prospectively evaluate the efficacy of routine ultrasound-guided fine-needle aspiration cytology (FNAC) of thyroid nodules in an endemic area and to analyze the factors influencing it., Methods: Patients with thyroid nodules were randomly subjected to either conventional palpation-guided fine-needle aspiration cytology (PFNAC) or ultrasound-guided fine-needle aspiration cytology (USFNAC). The results of cytology were compared with the final histopathologic diagnosis in 112 patients who had undergone surgery. The performance of both methods was individually analyzed in solid nodules, cystic nodules, and solitary and multinodular goitres., Results: Overall, USFNAC showed a significantly higher sensitivity (83.3% vs 54.6%, p < .001), positive predictive value (100% vs 85.7%, p < .001), and greater diagnostic accuracy (96.5% vs 89.1%, p = .052) compared with PFNAC. The sensitivity of USFNAC was significantly higher compared with that of PFNAC in cystic and complex nodules (75% vs 50%, p < .001) but not in solid nodules (77.8% vs 75%, p > .05). USFNAC was more sensitive and more accurate than PFNAC for detection of malignancy in multinodular goitres (66.7% vs 50%, p < .05; 95.6% vs 86.2%, p < .05, respectively)., Conclusion: The superiority of "routine" USFNAC over PFNAC is mainly due to its better performance in cystic nodules and multinodular goitres. Hence, routine USFNAC can be recommended in areas where such lesions constitute the majority of thyroid nodules.

Factors that should be considered when studying the effect of dietary iodine in the development of thyroid cancer include pathological criteria, diagnostic techniques, screening programs, radioactive fallout, and standard of medical care in the studied population. In most surveys, papillary carcinoma forms the largest group of thyroid malignancies, both before and after iodine prophylaxis where an increase in the papillary:follicular carcinoma ratio is also noted. Undifferentiated carcinomas decrease after salt prophylaxis. In Salta, Argentina, the increasing incidence of clinically significant papillary thyroid cancer and the decrease of undifferentiated carcinoma after iodine prophylaxis are probably due to better access to health centers and consequent earlier detection of differentiated precursor tumors. Autoimmune focal and diffuse or Hashimoto's thyroiditis are linked to dietary iodine. Pathological studies made in different regions indicate that these types of thyroiditis occur more frequently in areas of iodine sufficiency than in areas of iodine deficiency, and increase after iodine prophylaxis both in non-goitrous and iodine-deficient areas like Salta, Argentina. An increase of lymphocytic thyroiditis could be linked to an increased incidence of primary thyroid lymphoma, and thyroiditis is more commonly associated with papillary carcinoma than with other types of thyroid follicular or C-cell derived carcinomas regardless of iodine intake.

Background: There are significant differences in the prevalence and behavior of differentiated thyroid cancers (DTC) in the iodine-deficient areas (IDA) and iodine-sufficient areas (ISA) of the world. The sodium iodide symporter (NIS), mediates active transport of iodide across the basolateral aspect of the thyroid follicular cell. However, no study had specifically addressed the issue of expression of sodium iodide symporter (NIS) in thyroid cancer specimens from IDA. The aim of the present study was to find an expression pattern of NIS in DTC in an iodine-deficient population, and to correlate it with histological subtypes, i.e., papillary carcinoma (PTC), follicular carcinoma (FTC), poorly differentiated carcinoma (PDTC), as well as with clinicopathological risk factors and iodine ((131)I) uptake by distant metastases., Methods: Immunohistochemistry was carried out in 39 cases of thyroid cancer (41 samples) including PTC (15), FTC (10), PDTC (9), anaplastic cancer (5), and resected metastases (2). Expression was correlated with the patient's age, sex, tumor size, presence or absence of extrathyroidal invasion, distant and lymph node metastases, and whole body radioiodine scan., Results: Overall, 61.8% of DTC patients showed NIS expression. There was no significant difference in expression rate between PTC (73.3%) and FTC (70.0%). However, expression was significantly less in PDTC (33.3%). There was no correlation between NIS expression and any clinicopathological risk factor (p > .05). The results of NIS expression were not concordant with (131)I uptake by metastases in 4 of 10 cases. (131)I uptake was absent in one case despite the finding that a metastatic site itself showed NIS expression in that case, whereas in the remaining 9 cases (131)I uptake was present although three cases did not show NIS expression., Conclusions: In our experience, overall expression of NIS was comparable to other studies from ISA. We conclude that expression may not accurately predict radioactive iodine (RAI) uptake by metastases.

An existing discrepancy between the prognostic estimations and real thyroid gland sickness rate due to radiation exposure from Chernobyl is an evidence of inaccuracy of radiation doses determination. The estimation of the thyroid cancer risks is based on the assumption that the absorbed dose is uniformly distributed in the organ. But functional asynchronicity specific for iodine metabolism in thyroid may modify a space distribution of the dose. The biochemical features of the contaminated areas including iodine deficit and goitrous endemia usually are not taken into account may influence the second phase of thyroid carcinogenesis that is the promotion due to increased accumulation of some carcinogenic microelements in goitrous thyroid. In the work we consider these problems which can make significant changes in radiation risks estimation.

Objective: Iodine intake is suspected to be a risk factor for thyroid cancer. Eastern Denmark is characterized by mild and western Denmark by moderate iodine deficiency, and this difference is associated with a 50% difference in the occurrence of goitre and thyrotoxicosis. The objective of the study was to determine whether the incidence of thyroid cancer differs between these two regions, as any difference would have important safety implications for the national iodine supplementation programme., Design and Methods: We studied all thyroid cancers notified to the Danish Cancer Registry in the period 1973-1997, focusing on the four most frequent subtypes: papillary, follicular, anaplastic and medullary thyroid cancer. A Poisson regression model was used with models of goodness-of-fit for age, period, sex., Results: No regional difference was found in the overall incidence of follicular (0.3% 100 000 person-years) or papillary (0.7% 100 000 person-years) thyroid cancer. A slight but nonsignificant increase in total incidence, resulting mainly from a significant increase in the incidence for the papillary subtype, was observed in both regions., Conclusion: The results suggest that modest differences in iodine intake do not affect thyroid cancer incidence or the distribution of subtypes.

Papillary (PTC) and follicular thyroid carcinoma (FTC) are known as differentiated thyroid carcinoma (DTC). Nevertheless, according to the UICC/AJCC (TNM) classification PTC and FTC are frequently analyzed as one cancer. The aim of this study is to show differences in outcome and specific prognostic factors in an iodine-replete endemic goiter region. Six hundred and three patients with DTC treated within a 35-year-period were retrospectively analyzed with respect to carcinoma-specific survival. Prognostic factors were tested for their significance using univariate and multivariate analysis. The histological type (PTC versus FTC) was found to be a highly significant factor - carcinoma-specific survival both in univariate (P<0.001) and multivariate analyses (P=0.003) was significantly different. Univariate analysis revealed patients' age, extra-thyroid tumor spread, lymph node and distant metastases, increasing tumor size, and the tall cell variant to be significant prognostic factors for PTC patients. Age > or =45 years, positive lymph nodes and increasing tumor size were confirmed as independent prognostic factors. Univariate analysis of FTC patients revealed age at presentation, gender, extrathyroidal tumor spread, lymph node and distant metastases, increasing tumor size, multifocality, widely invasive tumor growth and oxyphilic variant to be factors bearing prognostic significance. The presence of distant metastases and increasing tumor size could be identified as independent prognostic factors for FTC patients. This study shows distinctive differences in prognostic factors of PTC and FTC: independent factors predicting poor prognosis are age > or =45 years, positive lymph nodes and increasing tumor size for PTC, and distant metastases and increasing tumor size for FTC. PTC and FTC patients should be analyzed and reported separately.

Aims and Background: The aim of the present study was to test some hypothetical risk factors for anaplastic thyroid cancer., Study Design: A case-control study comprised 110 patients with histologically or cytologically verified anaplastic thyroid cancer and 110 hospital controls individually matched with cases by sex, age, place of residence and time of hospitalization. Univariate and multivariate logistic regressions were used for data analysis., Results: According to the conditional logistic regression analysis, the following factors were significantly and independently related to anaplastic thyroid cancer: history of goiter or thyroid nodules (odds ratio, OR, 37.55; 95% confidence interval, CI, 4.86-290.11), history of residence in endemic goiter area (OR, 2.56; 95% CI, 1.05-6.22), history of previous malignant non-thyroid tumor (OR, 5.51; 95% CI, 1.04-29.25), diabetes mellitus (OR, 4.06; 95% CI, 1.29-12.81) and low educational level (OR, 2.44; 95% CI, 1.17-5.06)., Conclusions: The results are in line with the current knowledge on factors related to thyroid cancer, except for the association between thyroid cancer and diabetes mellitus, which as far as we know has not yet been reported.

In the framework of the Thyroid initiative Papillon 2001 - 2002 thyroid nodules and sonographically detectable focal lesions with a diameter more than 5 mm were verified in 23.1% of 64.123 persons without a history of thyroid disease. The frequency of such findings was with 33.0% in 46-65 years old persons three times higher then in persons aged 18-30 years (9.6%). In the diagnostic workup thyroid cancer was detected in 15 patients operated on up to now (6 women and 9 men; papillary cancers in 12 cases, follicular cancers in 3 cases) The smallest tumor had a diameter of 1.3 cm, the mean diameter was 2.3 +/- 91 cm. In 3 patients the tumor had invaded the tissue beyond the thyroid capsule, in 4 cases multicentric growth was detected. Lymph node metastases were found in 7/15 cases and distant metastases in 2/15 cases. These result reveal, that thyroid cancer detected by chance may be relatively aggressive. In daily routine, sonographically detectable lesions with poor echogenicity, irregular margins or internal calcifications with a diameter of more than 1 cm should be clarified by fine needle aspiration biopsy.

A retrospective analysis of 215 differentiated thyroid cancers was undertaken to identify the various prognostic variables. There were 132 papillary and 83 follicular cancers; both histologic types occurred at an earlier age, with a male to female ratio of 1: 1.1 (signifies near parity in both sexes, in contrast to marked female preponderance in most of the reports and amongst benign thyroid disorders). There was a significant difference in the size of the primary tumours; 60/132 (45%) of papillary and 30/83 (36%) of follicular cancers were early T0-1 lesions and 20 (15%) papillary and 24 (29%) follicular cancers were advanced T3 lesions. Age did not affect the size of the primary tumour. Regional lymph node and pulmonary metastases were common in both types of cancer while distant metastases occurred more frequently in follicular cancers (p < 0.005). Following surgery, contralateral lobe recurrence in the remaining lobe was more common in the follicular cancer group, while loco-regional recurrence after near-total thyroidectomy was more frequent in the papillary cancer group (p > 0.05). Mortality in 26/132 (20%) papillary and 28/83 (34%) follicular cancer patients was high in both groups, but significantly higher in the follicular cancer group (p < 0.05). Although mortality among patients with papillary cancer was higher in patients older than 40 years of age (p < 0.05), age did not affect survival in patients with follicular cancer. Gender did not affect survival in either group. The extent of the disease at presentation was the most important determinant of survival, with mortality significantly higher among patients with T3N3M1 lesions (p < 0.001).

The natural history of thyroid cancer and thyroiditis in relation to iodine prophylaxis in the region of Salta, Argentina, where goiter is common was investigated over a time span of 40 yr. For analysis of thyroid cancer, the specimens were divided into two periods. The first 15 yr (59 cases), including 5 yr before prophylaxis, was compared with the second 25 yr (182 cases), a period well after salt iodination. Papillary carcinomas formed the largest group of tumors in both periods, with a significant increase in their proportion in the second period (44 vs 60%, chi(2): p < 0.05), while the percentage of follicular and undifferentiated carcinomas decreased and medullary carcinoma remained about the same. The ratio of papillary to follicular carcinoma rose from 1.7:1 in the first period to 3.1:1 in the second. Four thyroid lymphomas of non-Hodgkin's B-cell type occurred in the second period in females over age 50. A severe lymphoid thyroiditis was present in the two cases with assessable background thyroid tissue. The frequency of moderate to severe lymphoid infiltrate in females rose from 2 of 12 (16.6%) in the preprophylaxis period to 34 of 114 (28.0%) in the last 25 yr after prophylaxis. After salt prophylaxis, thyroiditis was more frequent in patients with papillary carcinoma (36.2%) than in those with nonpapillary tumors (14.7%) (chi(2), p < 0.02). These observations indicate that a high dietary intake of iodine may be associated with a high frequency of papillary carcinoma and thyroiditis, and that thyroiditis is more commonly associated with papillary carcinoma than with other thyroid tumors. The occurrence of non-Hodgkin's lymphomas only in the postprophylaxis period may be linked to an increase in thyroiditis.

Data concerning the incidence of latent thyroid carcinoma (LTC) in populations with endemic goiter are scarce. Despite the introduction of iodine goiter prophylaxis in the early sixties, iodine supply is still insufficient in Austria and goiter remains endemic. This is the first detailed study dealing with epidemiological features of LTC at autopsy in Austria. A total of 118 thyroid glands were included in the study. The glands were serially sectioned at 2- to 3-mm intervals, embedded in paraffin and histologically examined for the presence of LTC. In addition, the incidence and severity of lymphocytic thyroiditis (LT) were evaluated. Ten thyroids were found to contain LTC (8.6%). All were of the papillary type. The mean tumor dimension was 4.9 mm +/- 3.2, the smallest lesion measuring 1 mm. Only the largest tumor slightly exceeded the extent of a microcarcinoma and measured 10.5 mm. Multifocal disease was present in three cases (30%). The prevalence of latent papillary thyroid carcinoma (LPTC) was 6.6% (n = 4) in females and 10.5% (n = 6) in males. The mean age of the subjects with LPTC was 67.7 +/- 14.4 yr, range 37 to 77 yr. Goitrous thyroids were seen in 33 cases (28%): One gland was diffusely enlarged and 32 (27.1%) enlarged glands were nodular goiters. The overall prevalence of LT was 30.5% (n = 36) and the only type of thyroiditis observed was focal lymphocytic thyroiditis (FLT). There was no correlation between the presence of LPTC and goiter, the presence of FLT and the subjects' age and sex. The incidence of LPTC in Austria is similar to that in nongoitrous regions. The adult population at large seems to be uniformly exposed to factors involved in the initiation and early growth of papillary thyroid carcinoma (PTC). This suggests that the levels of iodine intake only play a minor role in the early phase of the carcinogenesis of PTC, but may be of some importance in the progression of LPTC to clinically evident PTC.

Olsztyn region (in the north of Poland) was classified as an iodine deficiency area with moderate endemic goiter prevalence. Following Chernobyl accident, the population had one of the highest radiation doses affecting thyroid. Aims of the study were to estimate the incidence of thyroid cancer and to determine its histopathological type. The register was carried out in Olsztyn region population including each newly diagnosed case of thyroid cancer in the calendar year. The personal data of patients were collected and processed on in computer. The incidence rate was calculated as the number of newly diagnosed cases in the calendar year per 100,000 inhabitants dependent on sex and age. The results were statistically evaluated. 242 newly diagnosed cases of thyroid cancer were registered including 8 young patients (up to 18 years of age) and 234 adults. The increase in the number of cancer cases was observed year by year. The predominant type of thyroid cancer was papillary carcinoma--66.8%. Follicular carcinoma constituted 17% of cases. A statistically significant increase of incidence rate was observed in women--from 2.8/100,000 to 11.1/100,000.

Although thyroid carcinoma is more common in the adult population, the risk of a nodule being malignant is greater in children. The aim of our present investigation was to ascertain the percentage of malignancy in nodular goiter observed in patients from the Lower Silesia region in the last 12 years. The examination included 60 children (12 boys and 48 girls) treated in our clinic from 1987 to June 1998. Age varied from 7 to 18 years (mean 14.8 +/- 2.4), most of them in the age group between 13 and 18 years. The following investigations were performed: TSH, T3, T4, thyroid ultrasonography, fine needle aspiration biopsy and Tc99 scintigraphy of the thyroid. Most of the patients were euthyroid; two children demonstrated pressure symptoms. All the patients were treated by operation. Histological examinations revealed the following: nodular goiter in 19 patients, cystic nodular goiter in 5, follicular adenoma in 20, fetal adenoma in 3, nodular goiter and follicular adenoma in 6, papillary carcinoma in 6, and follicular carcinoma in 1 patient. We concluded that an increased incidence of thyroid cancer has been noted in children with nodular goiter in Lower Silesia during the last 12 years. Thyroid cancer was observed mostly in patients with single nodules and was associated with a high risk of malignancy.

Background: The percentage of thyroid cancer cases attributable to specific risk factors can be calculated to focus preventive strategies. The per cent population attributable risks (PAR) for thyroid cancer were estimated in relation to history of benign thyroid diseases, history of radiotherapy, residence in endemic goitre areas and selected indicators of a poor diet, using data from a case-control study conducted between 1986 and 1992 in Northern Italy., Methods: Cases were 399 histologically confirmed incident thyroid cancers and controls were 617 patients, admitted to hospital for a wide range of acute, non-neoplastic, non-hormone-related diseases. The PAR were computed on the basis of multivariate odds ratios (OR) and on the distribution of risk exposure among cases, assuming they are representative of the general population of cases., Results: A history of benign thyroid disease accounted for 18.9% of cases, radiotherapy for 1.2%, residence for > or =20 years in endemic goitre areas for 2.4% of cases, and their combination for 21.7% of thyroid cancer cases; selected indicators of a poor diet accounted for 40.9% of thyroid cancer cases in this population. The combination of all factors considered explained over 57% of thyroid cancer cases in both sexes. The estimates for thyroid-related conditions were higher in women than men, whereas the opposite was true for dietary indicators. The overall PAR were somewhat higher in people aged > or =45 years (63.8%) than in younger subjects, and for follicular (69.1%) rather than papillary (53.7%) cancers., Conclusions: Exposure to a few simply identified and potentially modifiable risk factors or indicators (benign thyroid disease, residence in endemic goitre area and a poor diet) explained about 60% of thyroid cancer cases in this Italian population, indicating the theoretical scope for prevention.

Aims and Background: The aim of this study was to analyze the frequency of coexisting hyperthyroidism and thyroid malignancy in endemic goiter areas and review the current literature on the subject., Methods: During the period January 1984 to June 1998, 1853 patients were examined for hyperthyroidism at the Spedali Civili Hospital of Brescia, Italy; 512 (27.6%) subjects underwent surgery. Of these patients 108 (21%) had Graves' disease, 251 (49%) multinodular toxic goiter (MTG) and 153 (30%) uninodular toxic goiter (UTG)., Results: Malignancy was found in 24 (4.7%) patients: 19 females and 5 males with a mean age of 52.2 years (range, 21-76 years). The frequency of cancer in Graves' disease was 6.4%, 5 females and 2 males; in MTG 3.9%, 2 females and 8 males, and in UTG 4.4%, 7 females and 1 male., Conclusions: Our data confirm previous reports on the frequency of thyroid cancer in hyperthyroidism. This association is more relevant than previously suspected. The frequent coexistence of hyperthyroidism and neoplasia, demonstrated by our study and the most recent literature, underlines the importance of studying and excluding the possibility of neoplastic degeneration by means of a systematic approach.

Iodine deficiency disorders (IDD) are an important public health problem in India. It requires further refinement and improvements in thyroid disease diagnosis, especially in the early diagnosis of thyroid malfunctioning and risk assessment of autonomously functioning thyroid tissue. Scintigraphy with technetium-99m pertechnetate under exogenous or endogenous thyroid stimulating hormone (TSH) suppression provides the best results. There has been significant improvement in methodology in various laboratory investigations that have resulted from the application of newer luminescent techniques and gene technology in various thyroid function tests. TSH measurement especially by using second or third generation assays has ensured diagnostic accuracy and thyrotropin releasing hormone (TRH) test now almost always unnecessary. Determination of glycosaminoglycans in urine may become a helpful tool in the follow up of endocrine ophthalmopathy. The differentiation of blocking and stimulating TSH receptor antibodies is relevant when discrepant results are obtained with respect to thyroid function. Some newer imaging agents have been used in thyroid disease scintigraphy such as octreotide or in thyroid diseases diagnosis such as fluorodeoxyglucose. Both improve the detectability of thyroid cancer metastasis especially if radioiodine scan is negative.

Geographical differences have been demonstrated for the cancer incidence and histology of differentiated thyroid cancer. Iodine intake and specific external noxes, such as nitrosamine ingestion or external radiation are important factors. It is still questionable whether histologically identical differentiated thyroid cancers are prognostically different in low and rich iodine areas. Despite increased knowledge of molecular and genetic changes in differentiated cancer, the present therapy is primarily related to patient age, tumor stage and histology.

Iodized salt prophylaxis has been performed in Austria since 1963. Through this approach, mean urinary iodine excretion has been normalized to 144+/-23.5 microg/g creatinine per day. Thus Tyrol is no longer an endemic goiter area. We have analyzed the impact of iodized salt prophylaxis on thyroid cancer (TC) comparing data from the early 1960s with those corresponding to the period 1986 to 1995, when iodine supply was normalized. The study included 439 patients from Tyrol and Southern Tyrol. The incidence of TC in Tyrol has risen during the past decades from 3.07 between in 1957 and 1970 to 7.8 between 1990 and 1994 (CR/100000/year). We observed a rise in the percentage of differentiated adenocarcinomas (56% to 91.5%) with a predominance of papillary TC (54.4%) along with a decrease of anaplastic TC. In addition to these histological features, a shift to less advanced TNM stages, eg, T1-3, N0-1a, M0, was obvious, increasing from 29% to 72.2%, whereas advanced tumors, ie, T4 or N1b or M1, decreased from 71% to 28%. These changes have significantly improved prognosis. The current 5-year survival rate is 90.7% as compared with a rate of 73% in the 1960s; the values for 7-year survival are 89% and 48%, respectively. The marked effects of age, tumor stages, and histology on prognosis were confirmed with the Kaplan-Meier method. We conclude that together with normalization of iodine supply in an endemic goiter region the epidemiological profile of TC has changed. Even though the incidence of TC has risen, prognosis has significantly improved due to a shift towards differentiated forms of TC that are diagnosed at earlier stages.

A history of benign thyroid diseases has been associated with the risk of thyroid cancer. We have analyzed this issue using data from a case-control study conducted in northern Italy between 1986 and 1992 on 399 incident, histologically confirmed thyroid cancer cases and 617 controls admitted to the hospital for acute, nonneoplastic, non-hormone-related diseases. The overall multivariate relative risk (RR) estimates were 2.8 [95% confidence interval (CI), 0.6-12.4] for previous episodes of thyroiditis, 27.1 (95% CI, 6.5-111.9) for adenoma, 8.2 (95% CI, 3.5-19.1) for goiter, 3.8 (95% CI, 1.4-10.9) for hyperthyroidism, and 1.5 (95% CI, 0.4-5.1) for hypothyroidism when all histotypes were analyzed. The RR for any thyroid disease was 7.7 (95% CI, 4.6-12.8). A family history of thyroid disease was significantly related to thyroid cancer with an RR of 1.6. The RR for having resided in endemic goiter areas was 1.3 for < 20 years of residence and 1.6 for 20 or more years. These associations were somewhat stronger when only papillary, follicular, and mixed papillary/follicular cancers were considered. Analyses of data in separate strata of sex and age suggested that several benign conditions play a more important role in females and in subjects younger than 50 years. Results were similar to the overall ones when papillary and follicular carcinomas were considered separately. The population-attributable risk for any previous thyroid disease was approximately 20% in this Italian population. These results confirm that history of thyroid disease is a relevant indicator of subsequent thyroid cancer risk also in areas at relatively low prevalence of goiter and other thyroid diseases.

From 1971 to 1985 at the Ahmadu Bello University Hospital, Zaria, 245 patients with multinodular goitre were operated upon mostly for cosmesis. Clinically unsuspected malignancy was present in 50 (20 pc) of the resected specimens of which 26 were follicular and 20 papillary. This pattern conforms with the reports from other African Zones of endemic goitre where the frequency of cancer is lower in the clinically solitary nodular goitre. Thus, the management strategy ought to regard the multinodular goitre as pre-malignant and operations should be performed earlier on this account.

The primary role of iodine deficiency in goitrogenesis and the prevention and treatment of endemic goiter by iodine supplementation is firmly established. Unfortunately, implementation of iodine prophylaxis programs has met with considerable technical and socioeconomic difficulties. Besides, lack of knowledge concerning some of the other causative factors of endemic goiter has prevented development of appropriate measures for its complete eradication in those areas where goiter persists in spite of prolonged and adequate iodine supplementation. At present, no less than 5% of the world's population have goiters and associated disorders, resulting in a public health and socioeconomic problem of major proportions. Seventy-five percent of people with goiter live in less developed countries where iodine deficiency is prevalent. Goiter prevalence rates of more than 50% and the highest frequency of severe cases of iodine deficiency disorders, namely, cretinism, congenital hypothyroidism, and various degrees of impairment of growth and mental development are found in endemic areas with extreme iodine deficiency. Goiters are usually multinodular and of very large size, producing, on occasion, signs of compression that require surgery. Recurrence rates are as high as 25-30% and second surgery accounts for 16% of all thyroidectomies. Unfortunately, most of these goiters occur in areas with highly restricted medical and surgical facilities. Twenty-five percent of people with goiters live in more developed countries where goiter continues to occur in certain areas despite iodine prophylaxis. Iodine-sufficient goiters are associated with autoimmune thyroiditis, hypothyroidism, hyperthyroidism, and thyroid carcinoma. Goiter is of considerable surgical significance in iodine-sufficient endemic areas and, to a lesser degree, in nonendemic areas where it is called "sporadic" goiter. Recurrence rates of iodine-sufficient goiter are 10-19% following thyroidectomy. Since most of these goiters grow by mechanisms other than increased thyrotropin (TSH) stimulation, treatment with suppressive doses of L-thyroxine is inefficient and, because of possible complications, not recommended. Although Graves' hyperthyroidism is not directly related to endemic goiter, it does relate adversely with ingestion or administration of iodine. At present, Graves' disease is treated with 131I or antithyroid drugs in more than 90% of the cases. The incidence rates of papillary, follicular, and anaplastic thyroid carcinomas appear to be related to endemic goiter and iodine supplementation, with surgery being required in essentially all of these cases.

The study deals with the results of clinico-morphologic analysis of thyroid cancer in 351 patients who have been operated on in the Carpathian Mountain [correction of Prikarpatsky] region endemic for goiter over the period of 25 years. Certain peculiarities of thyroid cancer were established: relatively high occurrence of the disease, specific ratio of basic histologic subtypes, high frequency of early stage cases and regular concomitance of cancer with other thyroid pathologies. The importance of further studies into the epidemiology of thyroid cancer is emphasized.

Between 1970 and 1987, 20,028 fine needle aspirates (FNA) of the thyroid have been examined in the Department of Pathology of the University of Innsbruck, Austria. During this period 92 cases of anaplastic carcinoma and 16 cases of malignant haemangioendothelioma (MHE) of the thyroid were diagnosed. Forty-three out of these 108 highly malignant tumours of the thyroid underwent FNA pre-operatively (39.1%). Thirty-seven FNA contained numerous cells of a highly malignant tumour. Five specimens (11.8%) contained only necrotic material and inflammatory cells. In one case of an anaplastic carcinoma no malignant cells could be demonstrated in FNA. We conclude that pre-operative FNA of highly malignant thyroid tumours may contribute substantially to subsequent clinical management.

Environmental factors contributing to incidences of thyroid carcinoma are re-evaluated and emphasized in this study. Thyroid cancers appear to occur independent of endemic goiter, based on epidemiologic and histologic evidence. While environmental factors appear to be important, the specific etiologic agent has not yet been identified or suggested. The number of thyroid cancer incidences available from cancer registries are analyzed in an attempt to identify a specific environmental carcinogenic agent. The presence of active volcanoes that produce abundant lava is found to be the common denominator of Iceland and Hawaii, where the incidence of thyroid cancer is outstandingly high. Comparison with other areas with active volcanoes is made. The presence of a carcinogenic agent in the lava is postulated and its possible mode of action on humans through fish products is hypothesized.

The accuracy of fine needle aspiration (FNA) cytology of the thyroid was addressed in 142 nodular goiters from an endemic goiter region. The aspirations and their interpretation were based on the methodology of the Karolinska Hospital. For practical purposes, the follicular lesions were divided into type I (benign), type II (atypical benign) and type III (suspicious). Excluding the follicular lesions, the cytohistologic agreement for the whole series was 87%, with a correlation of 81.5% for carcinomas. The type I and type II follicular lesions were benign on histologic grounds; 39% of the carcinomas were detected in the type III follicular lesions. The 0.7% false-positive diagnoses increased to 15% when type III follicular lesions were included. No false negatives were recorded. These observations, together with the increase of surgically resected thyroid carcinomas after FNA was accepted as a diagnostic modality, indicate that FNA biopsy of the thyroid is an accurate diagnostic method and is useful in selecting patients for subsequent surgery in areas of endemic goiter.

Iodine prophylaxis was introduced to the moderately severe goitre endemic area in Salta, Argentina, in 1963. All thyroidectomies from a 20 year period were reviewed, and 148 thyroid malignancies carefully studied. The period from 5 to 15 years after iodization was associated with a lower frequency of follicular carcinomas and a higher frequency of papillary carcinomas than the period before and up to 5 years after prophylaxis. Lymphoid infiltration in the non-tumorous thyroid was relatively infrequent before iodine prophylaxis: it was much higher in each of the post-prophylaxis periods. These results, in agreement with other studies, support the view that an increased iodine intake is associated with an increased incidence of papillary carcinoma of the thyroid and thyroiditis.

An analysis of thyroid cancer morbidity was carried out in two adjacent areas of Sicily differing in iodine intake. A consecutive series of 911 patients with "cold" nodules from an iodine-deficient area (IDA) and 2537 from a control area (CA) were examined by fine needle aspiration and selected for surgery and pathologic examination. Malignancies were found in 27 of the patients (2.96%) from the IDA and in 139 patients (5.48%) from the CA. Based on a population survey indicating that "cold" thyroid nodules were 2.5 times more frequent in the IDA with respect to the CA, we calculated a prevalence of 127 thyroid cancers per 10(5) inhabitants in the IDA versus 93 in the CA (P less than 0.001). Moreover, follicular and anaplastic carcinomas were three times more frequent in the IDA than in the CA (75 versus 24 cases per 10(5) inhabitants, respectively). These studies indicate that iodine deficiency may be one factor in the development of certain thyroid malignancies in man.

From January 1962 through October 1975, 455 patients with single thyroid nodules were operated on at King Paul Hospital. Malignancy was proved in forty-three patients. The overall incidence of carcinoma was 9.5 per cent. A higher incidence of cancer was found in patients less than ten years of age (40 per cent), between eleven and twenty years of age (20 per cent), and more than sixty-one years of age (17.4 per cent). Malignant nodules were more frequent in males (17.5 per cent) than in females (8.3 per cent). Radioactive iodine scanning does not distinguish benign from malignant nodule. Solitary thyroid nodules require operative excision supplemented with replacement therapy.

A series of 41 poorly differentiated follicular carcinomas of the thyroid gland without histopathological features of medullary or papillary carcinoma and 9 cases of undifferentiated thyroid carcinoma of the small cell type (diagnosed between 1967 and 1983) were investigated immunohistochemically. Two poorly differentiated follicular carcinomas showed a considerable number of calcitonin-positive cells in addition to the weakly thyroglobulin-positive tumor cells. One of these cases revealed several areas with calcitonin-positive tumor cells with additional squamous metaplasia with keratinization. No medullary carcinomas could be demonstrated among the 9 cases previously diagnosed as undifferentiated thyroid carcinomas of the small cell type. From the epidemiological point of view the application of immunohistochemistry does not significantly increase the proportion of medullary carcinomas detected in our endemic goiter area. The incidence of medullary carcinoma remains surprisingly low when compared with nonendemic areas.

In total, 15,325 fine needle aspiration (FNA) biopsies of the thyroid were examined in the Department of Pathology of the University of Innsbruck, Austria, between 1976 and 1985, with the cytologic results histologically verified in 3,112 cases. Since (1) it is frequently impossible to distinguish benign from malignant encapsulated follicular thyroid tumors by cytologic criteria and (2) there is a high level of follicular thyroid carcinoma in our endemic goiter area, we have adopted a diagnostic strategy that accepts a high percentage of false-positive cytologic results in order not to miss highly differentiated follicular carcinoma. To avoid unnecessarily extensive surgical treatment, 1,079 intraoperative frozen section examinations of the thyroid were performed in the same time period in (1) patients with preoperative suspicious or positive FNA cytologic findings, (2) cases with suspicious clinical and anamnestic data and (3) tumors with a suspicious macroscopic appearance without preoperative FNA or with negative or unsatisfactory cytologic findings. In 48 cases (4.5%), the frozen section diagnosis had to be revised after examination of paraffin-embedded tissue. An intraoperative false-positive diagnosis was obtained in 3 cases (0.3%) while a false-negative diagnosis was made in 45 cases (4.2%). The main effort in examining frozen sections should be concentrated on avoiding false-positive errors, which can lead to unnecessary thyroidectomies.

A detailed examination of 281 patients who had undergone primary surgery for nodular formations in the thyroid was carried out. In most cases, up-to-date methods of preoperative diagnosis (thyroid scanning, diagnostic puncture followed by cytological examination and X-ray examination of soft tissues of the neck to detect calcinates in the gland) were employed. Thyroid cancer was detected in 18.1% of these cases, while background tumor process was not established in 2.1% of patients only. Cancer incidence rates were similar in the cases of single nodes (17.3%) and multiple nodes (19.3%) in the thyroid. Considering the high risk of cancer in the pathologically-altered thyroid tissue, extrafascial surgery for nodular formations rather than intrafascial (for ablastic reasons) should be indicated in patients living in areas where goiter is endemic.