Goiter Area Research Articles

Model of the athymic nude mouse for the study of benign goiter disease.

Since Shimosato et al., in the mid 70s transplanted for the first time thyroid carcinoma tissue onto nude mice, other research groups have made use of the nude mouse model for the investigation of xenotransplanted thyroid tissue. The use of this model for the investigation of benign goiters is briefly discussed in this article. Normal human thyroid tissue has been transplanted either as a control in experiments with benign and malignant goiter tissue, or for the study of thyroid tissue response to stimulators such as TSH or thyroid stimulating antibodies (TSAb). Thyroid glands from 8- to 10-week old human fetuses obtained at the time of legal abortion were cryopreserved in liquid nitrogen and successfully transplanted into nude mice. Moreover, all the variants of human benign goiter tissue have been xenotransplanted: tissue from nodular and diffuse goiters, hot and cold nodules or goiter areas, rapidly growing nodules, etc. Two examples of animal thyroid tissue xenotransplantation onto nude mice are briefly discussed: Nude mice bearing normal thyroid tissue transplants from 4 different species (man, rat, pig, guinea-pig) have been used for the study of the species specific effect of bovine TSH and TSAb. In studies aiming at elucidating the pathogenesis of hyperthyroidism, toxic goiter tissue from hyperthyroid cats has been transplanted. In methodological terms, these experiments have shown that surgically removed goiter tissue can be shipped by air in cell culture medium at 4 degrees C over long distances and then successfully transplanted.-Finally, cell lines such as the rat cell line FRTL-5 can be transplanted onto nude mice either as cell suspension or embedded in collagen, for example for the study of proliferation and folliculogenesis. Using the xenotransplantation model, function and proliferation, morphogenesis and differentiation, as well as thyroid autonomy and response to stimulators have all been studied in xenotransplanted human and animal thyroid thyroid tissue and cell lines under various experimental conditions. Although new research tools, for example transgenic animals, are now increasingly and successfully used, xenotransplantation still offers the possibility of addressing some specific questions which cannot be answered so easily with other experimental models. For example, studies with human tissue, involving drugs or radioactive tracers which cannot be applied to the intact human being, can relatively easily be performed with xenotransplanted human tissue and application of the drug or tracer to the host mouse. Or embryological development can be followed and studied using fetal thyroid (and other) tissue transplanted onto nude mice; here, of course, difficult ethical issues have to be considered. Finally, it should be mentioned that, although many scientific questions can be studied nowadays by cell culture or other in vitro systems, animal models are still needed. Extrapolation to the human being, however, should always be done with caution and we should always keep in mind that for the understanding of a human disease indeed human experimental models remain the goldstandard.

Etiology of Simple Goiter

imple goiter (SG), that is an enlarged nontoxic thyroidgland which is not the result of an inflammatory or neo-plastic process, although on the wane, remains a nearly globalproblem (1,2). Until increasingly employed iodization pro-grams significantly reduces its prevalence, the etiology as wellasthetherapyofbenignnontoxicgoitershouldremaininfocus.It is well accepted that sporadic or endemic SG (2,3), alongwith the other common thyroid diseases co-existing withgoiterincludingGraves’disease(4),toxicmultinodulargoiter,and Hashimoto’s thyroiditis (5), is a complex disease. Theseareallcommonandmultifactorialwiththeclinicalphenotyperepresenting the net effect of many contributing genetic andenvironmental factors. It has been difficult to disentangle en-vironmental influences from genetic susceptibility, progresshasbeenslowinrevealingcandidategenes,andlittleisknownof the roles of gene–environment and gene–gene interaction.AroleforgeneticfactorsintheetiologyofSGhaslongbeenrecognized. Familial aggregation is illustrated by the 5–10times greater prevalence of SG among the probands of firstdegree female relatives as compared with the backgroundpopulation (2,3). Subsequently, twin studies (3), demonstrat-ing a significantly higher concordance rate in monozygotic(53%,95%CI23–83%)thanindizygotictwins(18%,95%CI5–35%), have clarified that the familial aggregation is the resultof shared genes and not of shared environment. Our study ina nonendemic goiter area (3) estimated that heritability oradditivegeneticfactorsaccountedfor82%(95%CI,67–92%)ofcases, while specific individual environmental factors likelyaccounted for 18% (95% CI, 8–33%) of goiter development infemales. The influence of heritability decreases with the pres-ence of major environmental factors such as iodine deficiency(2). As a consequence, susceptibility genes are more easilydiscerned in nonendemic goiter areas. The pronounced influ-ence of heritability on thyroid size (6) and thyroid nodularity(7), with or without concomitant clinical goiter, strengthenstheconceptthatthereisaconsiderablegeneticinfluenceonthedevelopment of SG.A detailed account of the genetic influences on the devel-opment of SG is beyond the scope of this editorial. Mutationsand polymorphisms in the genes for thyroid peroxidase(TPO), thyroglobulin (Tg), sodium iodide symporter (NIS),and thyrotropin receptor (TSHR), however, all have a role (8–10). SG is polygenic, moreover, with no single gene beingeither necessary or sufficient for disease development. Thelimited studies to date suggest that the genetic backgroundvariesfromfamilytofamily.Furthermore,ourunderstandingof the interaction between heredity and environment is verylimited. There is a clear lack of longitudinal studies in indi-viduals with genetically based susceptibility to determinehow and when environmental triggers such as iodine defi-ciency or cigarette smoking influence the occurrence of SG.When studying this issue it is important to realize that SG isnot one single phenotype.The pronounced sex difference in prevalence of thyroiddisease, often 5–10 times more common in females, is puz-zling. Theoretically, a skewed X chromosome inactivation(XCI) pattern—which is probably genetically determined—andresultanttissuechimerismcouldofferanovelexplanationfor the female preponderance of thyroid disorders, includingthat of SG (11). The X chromosome harbors genetic markerslinked to SG (12) and a skewed XCI (i.e., predominant inac-tivation of the normal X chromosome) could result in ex-pression of X-linked diseases. When recently tested, thishypothesis was rejected (13). Intake of oral contraceptives,another potential explanation for the sex-related difference inprevalence of SG, is actually associated with a decreasedthyroid size (14).Whereas environmental influences can be modified whilegenetic background cannot, much of the current focus on theetiology and treatment of SG has been on identifying andcorrectingenvironmentalinfluences.Large-scalestudieshavedemonstrated the importanceof surprisingly small variationsiniodine intake notonly for the prevalence ofovert goiter butalso for the regulation of thyroid size in nongoitrous indi-viduals(15).Interestingly,arelativelysmallincreaseiniodineintake, for just a few years, leads to a measurable and signif-icant decrease in thyroid volume (15), suggesting that modi-fyingiodineintakemayrapidlyleadtoadecreaseinincidenceof SG and subsequently in overt nodular toxic goiter. Studiesof this kind, such as performed in Denmark (16), will un-doubtedly provide further evidence of the interaction be-tween genetic susceptibility and environmental triggers.Another modifiable goitrogen is cigarette smoking. Thereis abundant evidence of its importance, from both case–control studies and studies in discordant twin pairs (17,18).Large-scale studies have demonstrated an interaction be-tween low iodine intake and thiocyanate generating cigarettesmoking, offering an explanation for the effect and providinga means to eliminate one or more factors in the genesis ofgoiter (19).

No Link Between X Chromosome Inactivation Pattern and Simple Goiter in Females: Evidence from a Twin Study

Simple goiter (SG) comprises diffuse (DG) and nodular (NG) benign nonautoimmune nontoxic goiter. In nonendemic goiter areas, the ratio of females to males may exceed 5:1, indicating that gender and/or sex hormones may play a role in the etiology of SG in these areas. Theoretically, as shown for autoimmune thyroid disease, X chromosome inactivation (XCI) and resultant tissue chimerism could offer a novel explanation for the female preponderance of SG. To examine whether skewed XCI is associated with SG, we first compared XCI in 71 twin individuals with SG with that in 142 unrelated healthy control twin individuals, and then performed a within-pair comparison of XCI in 48 twin pairs discordant for SG. DNA was extracted from peripheral blood cells. XCI analysis was performed by predigestion of DNA using the methylation-sensitive enzyme Hpall, followed by polymerase chain reaction of the polymorphic CAG repeat of the androgen receptor gene. A polymerase chain reaction product is obtained from the inactive X chromosome only. The XCI pattern was classified as skewed when 80% or more of the cells preferentially inactivated the same X chromosome. Twin zygosity was established by DNA fingerprinting. The frequency of skewed XCI in female twins with SG, DG, and NG was 11% (8/71), 13% (6/46), and 8% (2/25), respectively, which was not significantly different from the prevalences in the corresponding control populations, 14% (20/142, p = 0.56), 14% (13/92, p = 1.00), and 14% (7/50, p = 0.71), respectively. Essentially, similar results were obtained when comparing the prevalence of skewed XCI in twin pairs discordant for SG (48 pairs), DG (30 pairs), and NG (18 pairs). In a sample of Danish female twins, we did not find evidence for involvement of skewed XCI in the etiology or the female preponderance of SG.

Dampak Suplementasi Pil Besi Selenium Terhadap Status Hormon Tiroid Dan Kadar Hemoglobin Pada Wanita Usia Subur Di Daerah Gondok Endemik

The Effect of Combination of Iron and Selenium Supplementation on the Status of Thyroid Hormone and Haemoglobin Levels of Child Bearing Age Women In Endemic Goitre Area. Background: Iodine Deficiency Disorder (IDD) and Iron Deficiency Anemia (IDA) still considered as a public health problem in Indonesia. It is possible that some people in endemic goiter area not only suffering from IDD but also IDA, particulary among Childbearing Age Women (CBAW). Based on the national household survey (SKRT, 2001), it was reported that the prevalence of IDA among CBAW in Central Java, 22.4%, while in Cianjur District was 36.6%. Iron deficiency not only caused the decreament of hemoglobin value, but also decreased the Tyroxin (T4) and triiodotironin (T3) hormon syntesis. The trace element which has important role for iodine metabolism is selenium (Se). So far IDA and IDD control programme in Indonesia have been conducted separately, by means not integrated in strategy and not using combination of iron and selenium supplementation. Objectives: The main objectives of this study are to find out the possibilities of integrated solution of IDD and IDA. To determine the effect of combination iron and selenium supplementation to iodine status and Hb level of CBAW in the endemic goiter area. Methods: Study design was randomized control trial. The study was conducted in Cangkringan Subdistrict of Sleman District of D.I. Yogyakarta. A total of 96 CBAW were randomly assigned into 3 groups. Each group received different treatment, but before starting, all subjects were received pirantel for deworming. Group A (n=31) received 400 mg of iodine (2 capsules) + ferrosulfate (60 mg elemental iron + 0.25 mg of folic acid) + 420 ug of selenium (yeast selenium); group B (n=31) received 400 mg of iodine + ferrosulfate and group C (n = 34) received 400 mg of iodine only (control group). Two capsules of iodine were given once in the beginning of study to all subjects, while ferrosulfate and selenium were given twice a week for 16 weeks. Data of hormon thyroxin (serum T4) and Hb was collected before and after intervention. Data of socialeconomi and selenium were collected at the first of study. Results: It was revealed that before treatment there were no significant difference of the average of Hb levels and the median value of serum T4 amongs 3 groups of study (p> 0.05). After 16 weeks intervention there were thyroid hormone status improvement (serum T4) to all groups as follows: group A (100%), group B (80%) and group C (66.7%) respectively. Conclusions: After 16 weeks intervention of iron and selenium preparate to CBAW who had received iodine supplementation, was able to improve status of thyroid hormone (serum T4) higher than to those who received iodine only (33.3%). The increment of Hb levels of CBAW who received iron and selenium supplementation (group A) was lower than those who received iron only (group B). Keywords: Childbearing Age Women, IDD, IDA, anemia and selenium.

Diagnostic Controversies in Vascular Proliferations of the Thyroid Gland

Vascular lesions are one of the most controversial issues in thyroid pathology. The differential diagnosis includes benign lesions on one side, i.e., endothelial reactive hyperplasia (Masson's "hemangioma") in goiter and hemangioma, and malignant tumors on the other, i.e., angiosarcomas and undifferentiated (angio)sarcomatoid carcinomas. Benign reactive endothelial hyperplasia with atypias mimicking malignant tumors may occur in long-standing nodular goiter, as a result of spontaneous hemorrhage followed by granulation tissue and fibrous organization. Alternatively, it may follow a fine-needle aspiration biopsy (FNAB) procedure. Angiosarcoma is a rare primary malignant thyroid tumor, mainly observed in endemic goiter areas displaying morphologic and phenotypical similar to those typical of angiosarcomas in other locations (including focal cytokeratin expression). The distinction between angiosarcoma and (angio)sarcomatoid anaplastic carcinoma is difficult and the true existence of angiosarcoma has been challenged. Other extremely rare vascular lesions or mimics in the thyroid include benign hemangioma and pseudo-angiosarcomatous variant of medullary carcinoma. The differential diagnosis between benign and malignant vascular conditions in FNAB material is extremely challenging, and the cytopathology report should be remarkably cautious, especially in poorly cellular and highly hemorrhagic cases: atypias in endothelial cells are not per se indicative of malignancy, being a common feature of reactive endothelial hyperplasia in infracted goiter nodules as well.

Evaluation of Iron in Serum and Urine and their Relation with Thyroid Function in Female Goitrous Patients

In many developing countries, women are at high risk of goiter and iron deficiency anemia (IDA). Iron deficiency adversely affects thyroid metabolism and may decrease the efficiency of thyroid hormones in areas of endemic goiter. The aim of the present study was to compare the level of iron (Fe) in biological samples (serum and urine) and serum thyroid hormones, thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxin (FT4) of goitrous female patients (GFPs; n = 69) with those of nongoitrous women as control subjects (n = 117), age range 21-45 years. The biological samples were analyzed for Fe concentration using flame atomic absorption spectrophotometer, prior to microwave-assisted wet acid digestion. The validity and accuracy of the method was checked by the certified sample and with those obtained by conventional wet acid digestion method on the same CRM and real samples. The overall recoveries of Fe in serum and urine were found in the range of 97.2-98.6% of certified values. The results of this study showed that the mean values of Fe in serum and urine samples of GFPs were significantly reduced as compared to control subjects (p = 0.002 and p = 0.015, respectively). The mean values of FT3 and FT4 were found to be lower in GFPs than in the age-matched healthy control women; in contrast, high mean values of TSH were detected in GFPs (p = 0.003). There was a positive correlation between serum Fe concentration and TSH (r = 0.85, p = 0.01), FT3 (r = 0.95, p = 0.003), and FT4 levels (r = 0.98, p = 0.007) in GFPs. It was observed that iron deficiency is prevalent in GFPs, so the need of Fe supplementation will be required to improve the efficacy of thyroid metabolism in goitrous women.

Effectiveness of the iodine prophylaxis model adopted in Poland

Most of the Polish territory has been classified as an iodine-deficient and endemic goiter area according to the International Council for Control of Iodine Deficiency (ICCIDD) criteria. In 1997 the obligatory model of iodine prophylaxis was implemented. Our investigations were aimed at the effectiveness of iodine prophylaxis in Poland. We assessed urinary iodine excretion and goiter prevalence in 5663 children aged 6-12 yr. The population of children from the same 27 schools was investigated from 1992 to 1994 (1406 girls and 1244 boys) and from 1999 to 2005 (1563 girls and 1450 boys) using identical laboratory and ultrasound methods. We found significant increase in iodine urinary concentration (median 52 microg/l vs 93 microg/l, p<0.001) with accompanying drop in goiter prevalence (29.6% vs 5.2%, p<0.001) after implementation of iodine prophylaxis. Iodine excretion distribution changed significantly after 1997 with an increase in the percentage of children with iodine urinary concentration above 100 microg/l from 10.8% to 45.4%, respectively. A significantly higher iodine urinary concentration was observed in lowlands compared to uplands both before and after implementation of iodine prophylaxis (median, 50 microg/l vs 57 microg/l and 86 microg/l vs 114 microg/l, respectively, p<0.001). The goiter prevalence did not differ between girls and boys from 1992 to 1994 (28.8% vs 30.5%, p=0.35) and 1999 to 2005 (5.5% vs 4.9%, p=0.45). Implementation of the new model of iodine prophylaxis in Poland in 1997 has led to significant increase in iodine urinary concentration and decrease in goiter prevalence among Polish schoolchildren. In the youngest group of children (6-8 yr olds), prevalence of goiter decreased to 3.2%--i.e. below endemic levels.

Early recognition of potential hyperthyroidism in endemic goitre areas (author's transl)

Equal amounts of autonomous thyroid tissue were found with the same frequency before and after 40 years of age in eumetabolic patients in endemic goitre areas. A tentative diagnosis of thyroid autonomy can be made already in euthroid patients with an 80% accuracy by combined estimation of an equivalent of free thyroxine and iodine uptake. The equivalent is taken from determination of thyroid pertechnetate uptake by quantitative scan evaluation. Proof of autonomy is established by the suppression test which in a prolonged fractionated form also permits estimation of the amount of functioning autonomous tissue. There is a linear correlation of technetium thyroid uptake after suppression and the volume of autonomous thyroid tissue. As free thyroxine increases after iodine intake of sufficient amount and duration in proportion with the volume of autonomous tissue, prognosis appears possible: patients with autonomous thyroid tissue above a "critical" volume can be expected to develop hyperthyroidism in case of sufficient iodine uptake. Iodine salt prophylaxis however does not induce hyperthyroidism in patients below 50 years of age provided that the daily additional iodine intake does not exceed 100 micrograms.

Goiter epidemiology in South Tirol

To ascertain the prevalence of goitre among schoolchildren in South Tyrol (uncontrolled voluntary iodine salt prophylaxis), the size of the thyroid gland was determined by palpation and ultrasound in 1,013 of 1,224 children, aged 6 to 14 years (547 boys, 466 girls), selected by statistically criteria. At the same time, to assess thyroid function, total and free fractions of T3 and T4, and TSH were measured, while iodine supply was determined by measuring urinary iodine. Stage Ia goitre was diagnosed by palpation in 157 children, stage Ib in 18 and stage II in two (goitre prevalence of 1.97% according to WHO criteria). Mean thyroid volume as determined by ultrasound was 4.26 (0.8-23.4) ml. As expected, it increased with age and body surface area: it was 2.55 +/- 0.49 ml in 6-year olds, 3.83 +/- 0.42 ml in 10-year olds and 6.42 +/- 0.69 ml in 14-year olds. Iodine excretion (143.8 [4.1-984.8] micrograms iodine/g creatinine) indicated adequate iodine supply to the tested subjects. South Tyrol is thus, according to WHO criteria, no longer an endemic goitre area. The voluntary use of iodinated cooking salt and changed food habits have probably effected this change in goitre epidemiology.

Expression of Cytokeratin 19 in the Diagnosis of Thyroid Papillary Carcinoma by Quantitative Polymerase Chain Reaction

To examine cytokeratin 19 (CK19) expression levels by immunostaining for protein and quantitative reverse-transcription polymerase chain reaction (qPCR) for messenger RNA in thyroid surgical specimens from patients with papillary carcinoma (PC) and other types of thyroid lesions. A total of 54 randomly selected postoperative thyroid tissue samples were collected for formalin-fixed paraffin-embedded sectioning or flash-frozen total RNA extraction for complementary DNA synthesis (or both). Tissue sections were stained for CK19 expression with use of a specific monoclonal antibody. qPCR was performed on synthesized complementary DNA with sequence-specific primers for human CK19 in conjunction with ribonucleoprotein S18 for normalization. CK19 immunostaining was diffuse and intense in all PC lesions and considerably less in specimens that harbored both Hashimoto thyroiditis (HT) and PC. CK19 immunostaining was mostly absent in areas of multinodular goiter (MNG), with occasional focal staining. HT and Hürthle cell adenoma were essentially negative for CK19 immunostaining, except for weak staining in focal areas. Analysis of CK19 gene expression by qPCR revealed that the PC samples tested (n = 21) had significantly higher levels in comparison with all other groups (P < 0.0001). Furthermore, PC had a 32-fold mean level increase in CK19 expression in comparison with CK19 expression in MNG. Hürthle cell adenoma (n = 5) and HT (n = 7) lesions were similar to MNG in CK19 expression, with some overlap of CK19 between HT and PC. The data indicate that expression of CK19 by qPCR is a quantitative method for distinguishing PC lesions from other types of thyroid lesions, in contrast to the more qualitative immunohistochemistry. Moreover, qPCR of CK19 is a valid method that could be used as an ancillary tool in diagnosing thyroid cancer. The expression of CK19 by qPCR may be adopted, in combination with other markers, for molecular definition of the various subtypes of thyroid lesions assessed by fine-needle aspiration biopsy in the preoperative diagnosis of thyroid lesions.

THYROID MALIGNANCY

Objectives: (1). Audit of our one year experience of management of thyroidcarcinoma in accordance with latest approved guidelines. (2) To point-out high risks of malignancy in population withthyroid diseases. Design: Prospective study. Setting: Surgical Unit-IV of DHQ Hospital Faisalabad with cooperationof Department of Pathology, Punjab Medical Collage, Faisalabad. Period: From 2000– 2001. Patients &amp; method. Allpatients irrespective of age and sex with suspicious of thyroid malignancy were included in this study . Out of total 56patients of thyroid diseases 13 cases were proved thyroid carcinoma on histopathology. Results: Carcinoma of thyroidwas found more common in females. Papillary carcinoma was found in early age group. Follicular carcinoma was foundin younger age group. All patients with anaplastic carcinoma were above, the age of 50 years. Total thyroidectomy wasfound the treatment of choice for the management of carcinoma thyroid. Modified neck dissection was done in selectedcases. We offered lobectomy for one patient with young age with 1.5cm lesion in one lobe. Most patients were placedon TSH suppression thyroxine therapy. Postoperative follow– up was done for one year. The most important prognosticfactor was age of patient, size, type and extent of tumor. Another important factor was the treatment of the diseaseoffered to the patient. Conclusions: Screening programme at least in goitrous areas should be done to detectmalignancy at early stage and then early management should be offered in hope of good survival and least morbidity.

Smoking and environmental iodine as risk factors for thyroiditis among parous women

To elucidate whether exposure to some environmental factors, i.e. cigarette smoking and iodine deficiency influence the risk of thyroiditis. We identified a cohort of 874, 507 parous women with self-reported information on smoking during pregnancy registered in the Swedish Medical Birth Registry from September 1983 through December 1997. Hospital diagnoses of thyroiditis (n = 286) and hypothyroidism (n = 690) following entry into the cohort were identified by record-linkage with the national Inpatient Registry. The hazard ratio (HR) of smokers compared to non-smokers and the corresponding 95% confidence limits (CL) were estimated by Cox regression. Smoking was inversely associated with risk of overt thyroiditis (adjusted HR = 0.72; CL = 0.54-0.95), even when diagnoses of primary hypothyroidism were included. However, a diagnosis of thyroiditis within 6 months from a childbirth was positively associated with smoking (adjusted HR = 1.88; CL = 0.94-3.76). Being born in areas of endemic goiter was not associated to hospital admission for thyroiditis. Thyroiditis patients who were smokers had more often than non-smokers a co-morbidity with other autoimmune disorders. Smoking may increase the risk of thyroiditis occurring in the post-partum period and influence the clinical expression of other thyroiditis, especially when occurring as part of a polymorphic autoimmune disease.

Evaluation of endemic goiter prevalence in Bulgarian schoolchildren

Iodine deficiency is a major health problem worldwide. The environment of the Balkan countries, including Bulgaria, is distinguished for its low iodine content. In 1994, the strategies for the prevention and control of iodinedeficiency disorders were actualized in Bulgaria and universal salt iodization and supplementation for the risk population groups (schoolchildren, pregnant women) were introduced. The aim of this study was to assess the effectiveness of the iodine prophylaxis in schoolchildren, living in an endemic for goiter area after the introduction of salt iodization in Bulgaria. For this purpose, the goiter prevalence and iodine status in 483 schoolchildren (274 boys and 209 girls) aged between 8 and 15 yr, living in an endemic for goiter area in Bulgaria were evaluated. Despite the normalization of iodine supply, mild iodine deficiency on the basis of goiter prevalence (16.15%) and urinary iodine excretion was found. These data indicate the need for reevaluation of the national strategy for prevention of iodine deficiency.

The Influence of Iron Status on Iodine Utilization and Thyroid Function

Despite significant progress, deficiencies of iron and iodine remain major public health problems affecting > or =30% of the global population. These deficiencies often coexist in children. Recent studies have demonstrated that a high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodized salt programs. These findings argue strongly for improving iron status in areas of overlapping deficiency, not only to combat anemia but also to increase the efficacy of iodine prophylaxis. The dual fortification of salt with iodine and iron may prove to be an effective and sustainable method to accomplish these important goals.

The incidence of recurrence and hypothyroidism after radioiodine treatment in patients with hyperthyroidism in Trakya, a mild iodine deficiency area, during the period 1991–2003

The purpose of this retrospective study was to evaluate the incidence of recurrence and the success of radioiodine treatment (RIT) in the Trakya region of Turkey, an area with mild iodine deficiency, and to compare the effect of dose regimen selection (fixed (FD) or calculated dose (CD)) on treatment success. The study sample included 148 patients (40 male, median age 50) treated with radioiodine between the years 1991-2003. Patients were categorized into three diagnostic groups: Graves' disease (GD) (n = 65), solitary toxic adenoma (TA) (n = 29), and toxic multinodular hyperthyroidism (TMH) (n = 54), and each divided into two subgroups according to treatment method; the first group was treated with a FD of 370 MBq (10 mCi), and the second with CD. The largest group was GD (44%), followed by TMH (36%). Median duration of follow-up was 28 months (range 6-147). FD was given to 52.7% of all patients and CD was given to 47.3%. There was a partial difference in the dose regimen between all groups, but did not reach statistically significant levels (FD vs. CD: 65%-35%; 38%-62%; 46%-54%; GD, TA, TMH respectively, p > 0.05). Total cure rate in FD and CD was 46 (59%) and 37 (52.9%), respectively. The rates of hypothyroidism for GD, TA, and TMH groups were 28 (43.1%), 6 (20.7%) and 16 (29.6%), respectively. The incidence of hypothyroidism did not vary significantly between any groups (p > 0.05). At the end of the follow-up period, a total of 104 patients (70.3%) were treated successfully. There was no significant difference in the cure rate between any groups (p > 0.05). The treatment success in all groups and subgroups did not differ significantly between FD and CD. Our lower cure rate than in previous studies may be related to iodine deficiency. Higher doses of radioiodine may be required to increase final treatment success in endemic goiter areas. If this true, dosimetry and calculated dose regimen would be required in all groups of patients instead of an FD concept. However, our findings should be verified in larger series of patients, with longer follow-up period, and urinary iodine concentration measurements.

Cigarette smoking and the risk of goitre and thyroid nodules amongst parous women

To clarify the mechanisms by which smoking is associated to toxic and nontoxic goitre and thyroid nodules. Cohort study. Sweden. A cohort of 874,507 parous women identified through the Medical Birth Registry, with smoking behaviour assessed through self-reported information at the first pre-natal visit, and follow-up between 1983 and 1997. Hospital diagnoses of toxic and nontoxic goitre and thyroid nodules, identified by record-linkage with the national Inpatient Registry. Cox regression was employed to estimate the hazard ratio (HR) of smokers compared with nonsmokers and the corresponding 95% confidence limits (CL). There was a significantly increased risk of goitre and nodules amongst smokers. The positive association was stronger for toxic (age adjusted HR = 1.94, CL = 1.74-2.16) than for nontoxic goitre and nodules (age-adjusted HR = 1.26; CL = 1.14-1.38). There was generally no clear risk trend with regard to amount smoked (below and above 10 cigarettes per day). Elevated body mass attenuated these associations, whilst being born in Swedish areas of endemic goitre enhanced the association with nontoxic goitre and nodules. Smoking enhances the risk of thyroid goitre and nodules requiring hospital admission. Iodine deficiency and body weight are likely to be important modifiers of the risk of thyroid hyperplastic diseases amongst smokers.

The effects of taking chronic nitrate by drinking water on thyroid functions and morphology

Nitrate incorporation in humans takes place via drinking water and food. The water used for drinking and cooking in the goitrous areas is high in nitrate content. The aim of the present study was to evaluate both chronic effects and the dose-response relationship of nitrate on thyroid functions. A total of rats were divided into 5 work groups and sodium nitrate was added to their drinking water in different concentrations (0, 50, 100, 250 and 500 mg/l) over a 30-week period. The radioiodine uptake of thyroid was decreased in the 50 mg/l nitrate group, whereas it was increased in the 250 and 500 mg/l nitrate groups as compared to control. All hormones of thyroid gland except total thyroxine and thyroid-stimulating hormone were decreased in the 50, 250 and 500 mg/l nitrate groups. However, the level of total thyroxin was increased in the 100 mg/l nitrate group. Thyroid gland weights were increased in all experimental groups. Histomorphological changes were observed in the 250 and 500 mg/l nitrate groups. These findings suggest that nitrate impairs thyroid function involving the hypothalamo-hypophysio-thyroid axis. This observation could contribute to the current discussion about the acceptable daily intake of nitrate, as well as drinking water nitrate standard safety margins.

HUBUNGAN KADAR SENG SERUM DENGAN TINGGI BADAN ANAK SEKOLAH DASAR PENDERITA GAKY

The incidence goiter starts to the extend in Urban area. Not all Elementary School children with goiterexperience of pursued growth. This indicates that besides low iodine content, there are other elements which also influence growth. This research intends to study the relationship between zinc the level of serum and height on elementary school children (8 – 12 year) in endemic goitre areas, in Malang Municipality. Data ware collected with cross-sectional study from August to December 2000. Blood and urine sample of twenty  children of each group were examined for zinc serumand iodine urine concentration. Information about diet pattern, socio-economical condition were obtained by structured questionairre for mother and children.This research used Independent T-test, Person Correlation test, and Multiple Regression for statistics analysis. The result showed that: (1). There were significant relationships between energy (r= 0.364, p = 0.012); protein (r = 0.481, p = 0.001) and zinc intake (r =0.491, p = 0.001) with height; (2). There were significant difference in energy (p = 0.014), carbohydrate (p = 0.042), lipid( p = 0.014), protein (p = 0.003), and zinc intake(p = 0.004) between the two groups examined. The conclusion was that lower height for age was possibly ascribed to lack of energy, protein, iodine and zinc intake. Key words:zinc serum, iodine urine, height for age, and goiter

Reappraisal of the risk of iodine-induced hyperthyroidism: An epidemiological population survey

The occurrence of iodine-induced hyperthyroidism (IIH) has been reported after iodine supplementation from clinics and hospitals, but not following an epidemiologic survey. We studied the prevalence of thyroid derangement in a population following iodine supplementation. One yr after more than 75% of the population had been consuming 40 ppm iodized salt; information regarding history of endemic goiter and iodized salt production, distribution, consumption and monitoring were collected in four cities of the Islamic Republic of Iran. A total of 6048 subjects were randomly selected. All subjects were assessed for size of goiter, and urinary iodine and serum T4, T3, TSH, anti-thyroglobulin and anti-thyroperoxide were measured. Before iodine supplementation, all four cities were areas of endemic goiter. The rate of household consumption of iodized salt was 50, 75 and 90% in 1994, 1995 and 1996, respectively. Ninety-one percent of the salt samples contained 15-55 ppm iodide. Total goiter rate was 57, 62 and 68%; median urinary iodine was 188, 197 and 190 microg/l in the age groups of 6-18, 19-40 and >40 yr, respectively. Prevalence of clinical and subclinical hyperthyroidism was 0.34 and 0.41 and those of clinical and subclinical hypothyroidism were 0.51 and 1.07%, respectively. Nine point eight and 18% in the 19-40 yr age group and 17.6 and 25.6% in >40 yr old subjects had positive anti-thyroperoxidase and anti-thyroglobulin, respectively. This systemic epidemiologic study in an iodine deficient population showed that, following a well-executed iodine supplementation program, the occurrence of IIH is rare.

Surgery is the Procedure of Choice for the Treatment of Patients with Toxic Adenoma in an Endemic Goitre Area

Purpose : Toxic adenoma is one of the main causes of hyperthyroidism. We investigated the efficacy of surgery in the treatment of toxic adenoma.Methods : Serum thyroid stimulating hormone (TSH) measurement, ultrasound and scintigraphy of the thyroid were made for diagnostic purpose. The safety of surgery was evaluated by postoperative clinical course of patients. The efficacy of surgery was determined by the function of the remaining thyroid tissue.Results : The incidence of hyperthyroidism was 53% in surgically treated patients with nodular goitre in our iodine deficient region. The cause of thyrotoxicosis was toxic adenoma in 15 patients (14%). Suppressed serum TSH levels indicated the hyperthyroidism in all of 15 patients. Solitary solid adenoma was found by ultrasonographic examination, and solitary autonomous hot nodule by thyroid scintigraphy. Surgical treatment consisted of unilateral total lobectomy. It was the primary treatment in 13 patients. Two patients had surgery as secondary treatment after unsuccessful primary radioactive iodine application. The early postoperative clinical course of all patients was uneventful. Thirteen patients who had surgery as primary treatment had normal thyroid function postoperatively contrary to other two patients who became hypothyroid after having unsuccessful radioiodine therapy, and surgery as the secondary treatment. Conclusions : The incidence of hyperthyroidism and toxic adenoma is high in our surgically treated patients with nodular goitre. The diagnosis of toxic adenoma is not difficult by serum TSH measurements, and ultrasound and nuclear imaging of the thyroid. Surgery is effective and safe, and the treatment of choice for patients with toxic adenoma in order to control radically the hyperthyroidism and to achieve the goal of providing the euthyroid status.