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Context: Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis., Objective: The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF receptor-2 [VEGFR-2] and hypoxia-inducible factor-1α [HIF-1α] genes or their genetic interactions with the risk of nodular goiter development., Patients and Methods: 116 normal subjects, without any thyroid disease, and 108 subjects with nodular goiter [subjects with goiter and at least one thyroid nodule of > 1 cm of maximum size and in absence of signs of autoimmunity] were selected from a homogeneous population living in a mild iodine deficiency geographic area. Analyses were performed on germline DNA obtained from blood samples and VEGF-A rs3025039, VEGFR-2 rs2071559, and HIF-1αrs11549465 SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction [MDR] methodology was applied to investigate the genetic interaction between SNPs. Hardy-Weinberg equilibrium was performed., Results: None of the studied polymorphisms were individually associated with a higher risk to develop nodular goiter [P > 0.05]. The combination of the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms had the highest accuracy of 0.58 [P = 0.018] and the interaction of some genotypes was significantly associated with the risk of nodular goiter development., Conclusions: Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.

Background: Few data exist on the prevalence of female sexual dysfunction (FSD) in thyroid disorders., Aim: We evaluated FSD in women with thyroid diseases and in control age-matched healthy women to investigate the relationship between sexual function and thyroid hormones., Methods: One hundred and four women with thyroid diseases and 53 controls participated in the study. Eighteen with hyperthyroidism (Group 1), 22 hypothyroidism (Group 2), 45 Hashimoto's thyroiditis (Group 3), 19 nodular goiter (Group 4) underwent thyroid function evaluation and sonography. The Female Sexual Function Index (FSFI) assessed sexual function., Results: The prevalence of FSD was 46.1% in thyroid diseases and 20.7% in controls. Only in Group 4, the prevalence (68.4%) was significantly higher than in controls (p<0.005). The mean total FSFI score was 20.1 ± 7.1 in women with thyroid diseases and 25.6 ± 4.7 in the controls (p<0.001). Compared with controls, there was a significant decrease of desire in Group 2; desire, arousal and lubrication in Group 3; desire, arousal, lubrication, orgasm and satisfaction in Group 4. In thyroid diseases the prevalence of FSD was 53% and 42%, while in the controls was 55% and 20%, in menopausal and pre-menopausal groups, respectively. We found a significant inverse correlation between TSH and FSFI (r=-0.7, p=0.01) in Group 4, which showed the lowest FSFI score (17.8 ± 5.7) and the highest body mass index (28.4 ± 7.1 kg/m(2))., Conclusions: Women with thyroid diseases present a higher prevalence of FSD than controls. Although our findings suggest a higher impairment of sexual function in Group 4 and a role for TSH in FSD, further researches are needed.

The aim of this study was to assess the prevalence of non toxic goiter, difuse or nodular, in all Genoa's Country thyroid diseases. The authors have studied one non-random casuistry of 1980 Patients observed from time to time in the last decade in Ambulatory of Nuclear Medicine (Department of Internal Medicine of University of Genoa) working with Section of Hygiene of ASL of Genoa. Of 1980 patients, 1629 (83.63%) were females; 351 (16.37%) were males, aged 14-70 years. The mean age was 42.6 years. First observations regarded only born and old date residents in Genoa never subordinates to surgical. Actinic or pharmacological treatments to the thyroid. All patients have normal circulating hormones and TSH. Every subject was afflicted with un toxic goiter (diffuse, single nodular or multi nodular) assessed by clinical Examination, ultrasonography and thyroid uptake with 99mTc-pertechnetate. This pathology represents now the 66.6% of all thyroid diseases observed. The A.A. emphasized an absolute prevalence of non toxic goiter in females (84.2% of observations). The enclosed tables are created divided the casuistry for age correspondents to the several decades (for the II to VII the wais). By means of the test of Kolmogorov-Smirnov we have shaped two delineating curves the frequencies. Accumulated of feminine and male subjects. The results of our study support a advantage of the Females versus male subjects in the diffuse and in the multi nodular goiter, while in the Struma to Single nodular differences are meaningful absent.

Despite the observation that parity may increase the risk of thyroid carcinoma, very few studies have investigated the possible repercussion of parity on thyroid benign pathology. Recently, parity has been identified as one of the factors contributing to a larger thyroid size in healthy females. The aim of this work was to investigate a possible role for parity on the prevalence of multinodular goiter in iodine deficient areas. For this purpose, the reproductive histories of 2 cohorts of women, normal (Group I, 235 cases) and non-toxic multinodular goiter (NTMNG) affected (Group II, 274 cases) were compared. All subjects were euthyroid and had no previous history of thyroid function abnormalities. The number of full-term previous pregnancies (2.55+/-0.11 vs 1.77+/-0.10) and age (47.7+/-0.76 vs 42.3+/-0.83 yr) were found significantly higher (p<0.001) in multinodular goiter (MNG) patients than controls. Parity and age were found to be directly correlated (p<0.001), nevertheless the partial correlation coefficients demonstrated an independent and statistically significant difference for both variables between normal and NTMNG. Therefore, the independent effects of parity and age were further investigated. The effect of age on NTMNG prevalence seems to be weaker, in fact significant differences (p<0.001) for age between patients and controls were detected only when the effect of parity was absent (nulliparous), while with increasing gestations the effect of age disappeared. Our results indicate that age plays a minor role compared to parity which can therefore be considered as a stronger risk factor. In conclusion, the present study shows that, at least in iodine deficient regions, non-toxic multinodular goiter women show a statistically significant higher parity rate than healthy controls. Age may play a certain role but only when additional stronger risk factors are absent.

Toxic nodular goiter (TNG) is the most frequent cause of thyrotoxicosis in the elderly, specially in iodine deficient areas. Epidemiological studies have shown that in iodine deficient areas (Jutland) the incidence of hyperthyroidism is significantly higher with respect to areas with normal iodine intake (Iceland) and it is due to TNG. A careful epidemiological study recently carried out in Pescopagano, in southern Italy, an area characterized by a mild to moderate iodine deficiency, indicates that, in its natural history, nodular goiter contributes to the development of functional autonomy and eventually hyperthyroidism. Somatic activating mutations of the TSH receptor are involved in the pathogenesis of TNG. It is supposed that the prolonged iodine deficiency associated with chronic TSH stimulation increases the replication of follicular thyroid cells, and favor the appearance and expression of mutations of the TSH receptor gene. The clinical signs are usually more subtle than those observed in Graves' disease: a long phase of subclinical hyperthyroidism (normal circulating thyroid hormones and undetectable TSH levels) can precede the appearance of the symptoms. Cardiac symptoms are most frequent, (arrhythmia and atrial fibrillation). Thyroid scintigraphy in toxic multinodular goiter shows an uneven distribution of the radionuclide with multiple hyperfunctioning nodules and cold nodules. Thyroid US shows goiter with inhomogeneous solid nodules often with ill-defined borders. The treatment with antithyroid drug does not allow a permanent remission of hyperthyroidism, but its use is indicated to achieve euthyroidism before the definitive treatment. The definitive treatment is radioiodine or thyroidectomy.

Background: The association of hyperparathyroidism (HPT) with thyroid disease has long been known, but the mechanisms underlying such an association have not yet been clarified., Objective: To elucidate the main factors determining this combination of endocrine diseases, in a retrospective multicenter study., Methods: We retrospectively reviewed all patients referred for parathyroid scintigraphy in the period 1990-1999. A total of 487 patients in the age range 17-65 years were selected for the analysis (339 women and 148 men); group A included 241 patients with primary and group B 246 patients with secondary HPT., Results: A total of 124/241 patients in group A (51.5%), but only 92/246 patients in group B (38.2%) had thyroid disorders (notably nodular goiter) associated with HPT (P=0.0035). Thyroid disorders were evenly distributed throughout the entire 17-65 years age range in group A, but 17-40-year-old patients in group B had significantly fewer thyroid disorders than the older patients of the same group (15.5% compared with 43.3%, P<0.002), as expected in a general population. In patients with primary HPT there was no difference in the prevalence of thyroid disease between women and men, whereas the ratio of women to men in secondary HPT patients with thyroid disease was about 3:1., Conclusions: These results demonstrate an increased prevalence of nodular goiter in patients with primary rather than secondary HPT, and are consistent with a possible role of increased endogenous calcium concentrations (a hallmark of primary, but not of secondary, HPT) as a goitrogenic factor in patients with HPT.

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.

Nodular goiter is the natural evolution of nontoxic goiter, that may be endemic, sporadic or familiar. Iodine deficiency is the cause of endemic goiter, while genetical defects, impairing the thyroid hormone biosynthetic efficiency or altering the number and/or activity of growth factor receptors, play the major role in the pathogenesis of sporadic and familiar nontoxic goiter. The prevalence of nodular goiter is directly related to the degree of iodine deficiency that is still present in several areas of the world. In iodine deficient areas such as some Italian regions, nodular goiter is present in 25-33% of the population, its frequency increasing with age. In iodine sufficient areas the prevalence of nodular goiter is comprised between 0.4 and 7.2% high in iodine deficient areas and about 4% in iodine sufficient countries, its frequency increasing with the age. Dysphagia, dyspnea and coarsening of the voice may occur for esophagous, tracheal or laryngeal nerve compression, respectively. Iodine deficiency has little if any effect on the frequency of thyroid carcinoma, while, with regard to the histological pattern, it leads to an increased ratio papillary/follicular. Thyroid function is normal in uncomplicated nontoxic goiter. However, the evolution of nodular goiter is toward the functional autonomy of nodules that may result in thyrotoxicosis. Hypothyroidism is rare and is usually the result of thyroid autoimmunity. All the cases due to iodine deficiency can be prevented by an adequate iodine prophylaxis that can be accomplished in industrialized countries by the use of sale enriched in iodine.

A retrospective investigation of the surgical cases of seven hospitals in the Veneto region was made in order to assess the malignancy rate in thyroid nodular pathology, and the predictive value of scintiscanning with positive indicator.

The basic features of the most common endocrine pathology, the thyroid nodule are analysed. After a brief assessment of the incidence of the condition the problem of clinical and instrumental diagnosis is tackled with the aim of demonstrating the value and possibility of sub-clinical diagnosis of micronodules. The present work aims to identify the fastest, most efficient and cheapest diagnostic procedure.