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Introduction: Italy is still characterized by a mild iodine deficiency and is among the most intensive users of chemical products for agriculture in Europe. The aim of this study was i) to evaluate thyroid effects of exposure to mancozeb, a fungicide widely used in agriculture, in a sample of Italian grapevine workers, and ii) to verify whether the iodine intake may modulate the risk of thyroid disruption due to the mancozeb metabolite ethylenthiourea (ETU)., Methods: One hundred seventy-seven occupationally exposed male workers (29 from Chianti, a mild iodine deficient area, and 148 from Bolzano an iodine sufficient province) and 74 non-occupationally exposed male controls (34 from Chianti and 40 from Bolzano) were enrolled in the study. Serum biomarkers of thyroid function, as well as urinary iodine and ETU concentrations were assessed. Moreover all the recruited subjects underwent clinical examination and thyroid ultrasound., Results: Multivariate comparisons showed lower mean serum levels of FT4 in Chianti-workers as compared to Bolzano-workers. Moreover, an increased urinary iodine excretion (>250µg/L) was more frequently found among more exposed workers (ETU>20µg/L) than among less exposed ones and this effect was more pronounced in Chianti- than in Bolzano-workers. Chianti-workers also showed a significantly higher frequency of very low thyroid volume (≤6.0ml) as compared to controls., Conclusions: These findings showed a mild thyroid disrupting effect due to occupational exposure to mancozeb, more pronounced in workers residing in an area characterized by a mild to moderate iodine deficiency as compared to workers residing in an area covered by a long-lasting iodine prophylaxis program., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention., Summary: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency., Conclusion: Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.

Background: Iodine deficiency is the result of insufficient intake of dietary iodine and as a consequence causes multiple adverse effects. About 2 billion individuals in the world are affected by iodine deficiency. It has been found that the most effective way to control iodine deficiency is through the universal salt iodization. However, salt iodization alone may not be sufficient to assure adequate iodine nutrition. In most industrialized countries, excess consumption of salt has become recognized as a health risk. Therefore, biofortification of vegetables with iodine offers an excellent opportunity to increase iodine intake., Aim and Methods: The aim of this study was to test the efficiency of a new model of iodine prophylaxis in a group of 50 healthy volunteers through the intake of vegetables (potatoes, cherry tomatoes, carrots, and green salad) fortified with iodine. Each serving of vegetables consisted of 100 g of potatoes, carrots, tomatoes, or salad containing 45 mg of iodine (30% of the Recommended Daily Allowance), and the volunteers consumed a single serving of vegetables, as preferred, each day for 2 weeks. Urinary iodine (UI) excretion was measured before and after intake of vegetables., Results: The UI concentration measured in volunteers before the intake of vegetables was 98.3 mg/L (basal value), increasing to 117.5 mg/L during the intake of vegetables. Seven days after the discontinuation of vegetable intake, UI was 85 mg/L. UI concentration increment was 19.6% compared with the basal value; therefore, the difference was statistically significant (P = .035)., Conclusions: Biofortification of vegetables with iodine provides a mild but significative increase in UI concentration and, together with the habitual use of iodized salt, may contribute to improve the iodine nutritional status of the population without risks of iodine excess.

The aim of the study was to draw up a management protocol in thyroid surgery promoted by the Italian Association of Endocrine Surgery Units (Club delle UEC), shared by the experts and applied by the operators in the sector. The management protocols already presented in February 2002 and drawn up by the first Author of the present publication on the occasion of the current review were examined by the I Consensus Conference called on the topic by the Italian Endocrine Surgery Units. The conference comprised two distinct sessions, the first on 18 June 2005 within the framework of the 4th National Congress of the Club delle UEC in Naples, and the second on 17 September 2005 within the framework of the 8th Multidisciplinary Scanno Prize Meeting. A selected board of endocrinologists and endocrine surgeons, chaired by Aldo Pinchera and comprising the first nine Authors of this paper, examined the individual chapters in close collaboration with the other Authors, comparing their findings with the opinions of the experts cited in the text and submitting the consensus text for the approval of all those present. The diagnostic, therapeutic and healtcare management protocols in thyroid surgery approved by the I Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (Club delle UEC) and are subject to review by October 1, 2007.

Total body weight is usually employed to calculate the amount of l-T(4) to be administered in patients with thyroid diseases. The aim of this study was to evaluate the effect of body composition on l-T(4) requirements. Body composition was assessed by dual energy x-ray absorptiometry in 75 patients on TSH-suppressive l-T(4) therapy after conventional thyroid ablation for differentiated cancer. The mean daily dose of l-T(4) was lower in normal-weight (127.5 +/- 21.3 mug/d) vs. overweight (139.4 +/- 24.5) and obese (151.3 +/- 29.1) subjects. There was a much stronger association between the l-T(4) dosage and lean body mass (P < 0.001, r = 0.667) compared with fat mass (P = 0.023, r = 0.26). Measurement of regional tissue composition showed peripheral lean mass as the best correlate with the dose of l-T(4) (r = 0.679, P < 0.001) whereas no correlation was observed with peripheral fat mass. In conclusion, individual l-T(4) requirements are dependent on lean body mass. Age- and gender-related differences in l-T(4) needs reflect different proportions of lean mass over the total body weight. An estimate of lean mass may be helpful to shorten the time required to attain a stable dose of l-T(4), particularly in subjects with high body mass index values that may be due either to increased muscular mass or to obesity.

The meeting held in May 2014 in Würzburg, Germany, discussed the scope of the revision of the 1999 WHO guidelines for iodine thyroid blocking (ITB) by following the WHO handbook for guideline development. This article describes the process and methods of developing the revised, evidence-based WHO guidelines for ITB following nuclear and radiological accidents, the results of the kick-off meeting as well as further steps taken to complete the revision. [ABSTRACT FROM AUTHOR]

Background: Clinically overt Graves' orbitopathy (GO) is associated with Graves' disease (GD) in approximately 95% of cases, whereas the remaining 5% is observed in patients with hypothyroid autoimmune thyroiditis (AT) or without overt thyroid dysfunction (euthyroid GO). However, it is not known whether there is a difference in terms of GO phenotype between patients with GD and those with hypothyroid AT or without thyroid dysfunction, and hence this is investigated here. Methods: The study design was to evaluate retrospectively all consecutive patients with a recent manifestation of GO, seen at their first visit to a tertiary referral center over a period of 10 years. In total, 358 GO patients were studied, and all of them underwent GO assessment. Results: Of the 358 patients studied, 341 had hyperthyroid GD, 10 had AT with hypothyroidism, and seven had euthyroid GO. Age, sex, and smoking habits were similar in the three groups, as was the time since GO was first noticed (GO duration). The vast majority of patients had moderate to severe, active GO, as expected in a tertiary referral center. Exophthalmometry, eyelid width, clinical activity score (CAS), diplopia, and visual acuity did not differ between patients with GD and those with AT or euthyroid GO, suggesting that the GO phenotype was similar. Accordingly, the NOSPECS score did not differ between the three groups. Conclusions: The phenotype of GO is similar regardless of the underlying thyroid disease. Because this study was performed in a tertiary referral center, this conclusion can be restricted only to patients who develop moderate to severe GO. [ABSTRACT FROM AUTHOR]

Background: Graves' orbitopathy (GO) is thought to be related to one or more autoantigens present in the thyroid and in orbital tissues. Although this may not imply a quantitative relation between thyroid antigens and degree of GO, which in turn is a risk factor for a more pronounced GO, we postulated that the severity of GO may parallel the amount of thyroid tissue, namely, the size of the thyroid gland. This hypothesis is also based on the observation that patients with Graves' disease presenting with large goiters tend to have more severe hyperthyroidism. Thus, we evaluated retrospectively whether there is a correlation between the degree of GO at its first observation and, among other parameters, the thyroid volume. Methods: Eighty-six consecutive patients with untreated GO lasting for no longer than 24 months underwent an endocrinological and an ophthalmological evaluation, the latter including: exophthalmometry, eyelid width, clinical activity score (CAS), diplopia, and visual acuity. The overall degree of GO was ranked using the NOSPECS score as well as a modification of the NOSPECS score. The following parameters were considered for correlations: time since GO appearance, time since detection of hyperthyroidism, FT3, anti-thyrotropin receptor antibodies, thyroid volume, and cigarette-years. Results: Thyroid volume, but not the other parameters, correlated significantly by simple regression with exophthalmometry ( p=0.02) and CAS ( p=0.02). The standard NOSPECS score correlated with FT3 ( p=0.05), thyroid volume ( p=0.02), and cigarette-years ( p=0.03), by simple, but not by multiple regression analysis. The modified NOSPECS score correlated with thyroid volume ( p=0.007) and cigarette-years ( p=0.04) by simple regression, and with thyroid volume also by multiple regression analysis ( p=0.05). Conclusions: Thyroid volume correlates with the severity of GO at its first observation, especially with exophthalmometry and CAS. The finding is in line with a possible pathogenetic role of antigens shared by the thyroid and orbital tissues. Nevertheless, other mechanisms may explain this observation, including an overall more reactive immune system in patients with a large goiter, resulting in more severe thyroid and eye disease, regardless of the nature of the autoantigen, or whether it is shared by the thyroid and the orbit. [ABSTRACT FROM AUTHOR]

Germline mutations of thyrotropin receptor ( TSHR) gene determining a constitutive activation of the receptor were identified as a molecular cause of familial or sporadic congenital nonautoimmune hyperthyroidism (OMIM: 609152) (Nat Genet 7:396-401, ; N Engl J Med 332:150-154, ; Acta Endocrinol (Copenh) 100:512-518, ). We report the case of an Italian child subjected to the first clinical investigation at 24 months for an increased growth velocity; biochemical investigation showed high FT4 and FT3 serum values and undetectable thyrotropin in the absence of anti-thyroid antibodies; the thyroid gland was normal at ultrasound examination. Treatment with methimazole was started at the age of 30 months when her growth velocity was high and the bone age was advanced. DNA was extracted from her parents', brother's, and the patient's blood. Exons 9 and 10 of the TSHR gene were amplified by polymerase chain reaction and subjected to direct sequencing. In proband, a heterozygous substitution of cytosine to thymine determining a proline to serine change at position 639 (P639S) of the TSHR was detected while the parents and brothers of the propositus, all euthyroid, showed only the wild-type sequence of the TSHR gene. This mutation was previously described as somatic in patients affected by hyperfunctioning thyroid nodules and as germline in a single Chinese family affected by thyrotoxicosis and mitral valve prolapse. This constitutively activating mutation is able to activate both the cyclic AMP and the inositol phosphate metabolic pathways when expressed in a heterologous system. In conclusion, we describe the first case of sporadic congenital nonautoimmune hyperthyroidism caused by de novo germinal P639S mutation of TSHR. [ABSTRACT FROM AUTHOR]

Objectives To establish the role of new TSH receptor (TSHr) variants (P27T, E34 K, R46P, D403N, W488R and M527T) recently identified in children with congenital hypothyroidism (CH) or subclinical hypothyroidism (SH) with a thyroid gland of normal size. Design and measurements TSHr variants were obtained by mutagenesis. Wild-type (wt) and TSHr mutants were expressed in COS cells and cAMP assay, 125I-TSH binding and microchip flow cytometry analyses were performed. Results D403N and M527T mutants showed a lower cAMP response to bovine TSH (bTSH) with respect to the wtTSHr. R46P and W488R mutants did not show any response to bTSH stimulation in terms of cAMP production. The E34 K mutant showed a significantly lower cAMP response to stimulation with bTSH, while P27T had a lower cAMP response only to the highest dose of bTSH used. P27T, E34 K, D403N and M527T mutants showed a lower TSH binding capacity with respect to the wtTSHr. R46P and W488R mutants did not show any TSH binding. Conclusions E34 K, D403N, M527T, R46P and W488R TSHr variants seem to cause a functional abnormality of the receptor which is responsible for the observed phenotype. The P27T TSHr variant does not seem to play a functional role in the pathogenesis of CH and should be considered as a polymorphism. [ABSTRACT FROM AUTHOR]

Summary: We have recently hypothesized that structural and secretory components of the adult human thyroid gland maintain constant reciprocal and geometrical relationships, even if changes occur in the three-dimensional (3D) architecture of any of these elements. This means that thyroid morphology could be studied from the point of view of a 3D topology. As a consequence, we have investigated anatomical aspects that could support this assumption. In the present study, we show that the presence of a constant relationship can be demonstrated between the vascular arrangement of the gland, including the extension of intraglandular arterial fields, arterial anastomoses and arterial calibers, and the shape as well as volume of the thyroid. Specifically, a statistically significant difference has been found between the network amplitudes of the superior and inferior thyroid arteries in relation to either a conic or an ellipsoidal geometry of the thyroid lobe. In addition, a direct relationship has been implicated between the distribution of arterial anastomoses and the behavior of the lobe as a single hemodynamic unit. Finally, a statistically significant correlation has been observed between average arterial caliber of the inferior thyroid artery and thyroid volume. On the basis of these results, we propose a model of architectural assembly between stromal and parenchymal elements of the adult thyroid that might prove useful in designing a bioartificial gland ex situ. Potential clinical applications of this principle in regenerative medicine of other endocrine organs are highlighted. [Copyright &y& Elsevier]

Objective Genetic analysis of the TSH receptor gene in seven subjects with subclinical hypothyroidism (SH), in whom the diagnosis of autoimmune thyroid disease had been excluded by laboratory and instrumental techniques currently available. Patients Three families where different members (2 children and 5 adults) affected by SH were studied. Genetic analysis Genomic DNA was extracted from peripheral lymphocytes and the entire coding sequence of the TSHr gene was sequenced. pSVL-TSHr construct harbouring a Q8fsX62 insertion was obtained by site-directed mutagenesis. COS-7 cells transfected with wild-type and mutant receptor were used for binding studies, flow cytometry, and cyclic AMP (cAMP) determination. Results A four base pair (bp) duplication in position 41 (41TGCAins), leading to a premature stop of translation at codon 62 (Q8fsX62), was found to be heterozygous in the proband, the father and the sister in Family 1. In Family 2 the proband and the sister were heterozygous for the mutation D410N. In Family 3 the proband and the father were heterozygous for the mutation P162A. After transfection in COS-7 cells, the mutant receptor Q8fsX62 displayed a low expression at the cell surface, and a reduced response to bovine TSH (bTSH) in terms of cAMP production. Conclusions We identified TSH receptor mutations in seven members of three families with subclinical hypothyroidism. [ABSTRACT FROM AUTHOR]

Objective To analyse the coding region of PAX8 in individuals with congenital (CH) or post neonatal hypothyroidism due to dysgenetic (TD) or eutopic thyroid glands. Design and patients Forty-three children with CH and TD (13 agenesis, 23 ectopia, and seven hypoplasia), one subject with post neonatal onset of hypothyroidism and thyroid ectopia, 15 children with CH and eutopic thyroid glands and six euthyroid adults with thyroid hemiagenesis were enrolled as cases, along with 120 healthy individuals as controls. Measurements Exons 2–8 of the PAX8 were directly sequenced. HeLa and HEK293 cells were transfected with PAX8 wild-type ( PAX8-WT), mutant PAX8, p300, thyroid transcription factor 1 ( TTF-1) and thyroglobulin promoter pGL3 ( TG prom-pGL3). Synergism of TTF-1 with PAX8-WT vs. mutant and activity of PAX8-WT vs. mutant in accompaniment with p300 on TG prom-pGL3 were also assessed. The luminescence produced by PAX8-WT and mutant PAX8 was measured. Results Among patients and controls only a 15-year-old girl with thyroid ectopia showed a heterozygous transition of cytosine to thymine at position 674 in exon 6, which changed a conserved threonine at position 225 to methionine ( PAX8-T225M). Her father and sister harboured PAX8-T225M without abnormal thyroid phenotypes. PAX8-T225M and PAX8-WT similarly increased luciferase activity and had a similar synergistic effect with TTF-1. At 500 ng p300, however, PAX8-T225M could not significantly increase TG promoter activity when compared to PAX8-T225M alone, while PAX8-WT +500 ng p300 induction was significantly higher than PAX8-WT alone ( P < 0·001). Cotransfection of TTF-1 together with PAX8-T225M resulted in rescuing of the lack of synergism with p300. Conclusions PAX8 mutations in congenital hypothyroidism due to dysgenetic or orthotopic thyroid glands are rare. PAX8-T225M is probably a rare variant. [ABSTRACT FROM AUTHOR]

To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules.Retrospective analysis of patients treated with131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years.A total of 346 patients treated with131I in the years 1975–95, for a single hyperfunctioning nodule.Hypothyroidism was defined as TSH levels> 3·7 mU/l. Kaplan–Meier survival analysis was used to analyse permanence of euthyroidism after131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism.The cumulative incidence of hypothyroidism was 7·6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0·01), 24-th131I uptake (P < 0·05) and previous treatment with methimazole (MMI,P < 0·1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0·01).After 20 years of follow-up, 60% of patients treated with131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age,131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan. [ABSTRACT FROM AUTHOR]

Summary objective Iodide transport defect (ITD) is a rare disorder characterised by an inability of the thyroid to maintain an iodide gradient across the basolateral membrane of thyroid follicular cells, that often results in congenital hypothyroidism. When present the defect is also found in the salivary glands and gastric mucosa and it has been shown to arise from abnormalities of the sodium/iodide symporter (NIS). patient We describe a woman with hypothyroidism identified at the 3rd month of life. The diagnosis of ITD was suspected because of nodular goitre, and little if any iodide uptake by the thyroid and salivary glands. Treatment with iodide partially corrected the hypothyroidism; however, long-term substitution therapy with l-thyroxine was started. measurements Thyroid radioiodide uptake was only 1·4% and 0·3% at 1 and 24 h after the administration of recombinant human TSH. The saliva to plasma I[sup -] ratio was 1·1 indicating that the inability of the thyroid gland to concentrate I[sup -] was also present in the salivary glands. results Analysis of the patient's NIS gene revealed a 15 nucleotide (nt) deletion of the coding sequence (nt 1314 through nt 1328) and the insertion of 15 nt duplicating the first 15 nt of the adjacent intron. The patient was homozygous for this insertion/deletion, while both consanguineous parents were heterozygous. This deletion predicts the production of a protein lacking the five terminal amino acids of exon XI (439–443) which are located in the 6th intracellular loop. COS-7 cells transfected with a vector expressing the mutant del-(439–443) NIS failed to concentrate iodide, suggesting that the mutation was the direct cause of the ITD in this patient. conclusion In conclusion we describe the first Italian case of congenital hypothyroidism due to a new deletion in the NIS gene. [ABSTRACT FROM AUTHOR]

BACKGROUND Graves' disease and destruction-induced thyrotoxicosis can be discriminated on the basis of radioiodine uptake (RAIU); however, this test is contraindicated during lactation. In addition, not all institutions have the facilities to assess this parameter. OBJECTIVE To evaluate whether measurement of thyroid blood flow can be used to differentiate between Graves' disease and destruction-induced thyrotoxicosis. DESIGN AND INTERVENTION This Japanese study evaluated patients aged 14-70 years who had untreated thyrotoxicosis. A control group of healthy individuals was also assessed. Levels of serum TSH, free T4 and free T3 levels were measured by chemiluminescent immunoassay. Serum anti-TSH-receptor antibody ('TSH-binding inhibitory immunoglobulin'; TBII) levels were measured by enzyme-linked immunosorbent assay and the results were expressed as the percent inhibition of TSH binding, with a cut-off value of <15%.Thyroid volume and blood flow were measured by Doppler ultrasonography. RAIU was measured at 3 h and 24 h. Graves' disease was diagnosed in patients with elevated free T4 and free T3 levels, reduced TSH levels, high TBII levels, and/or high RAIU. Painless thyroiditis was diagnosed in the presence of elevated free T4 and free T3 levels for <3 months, and/or development of transient hypothyroidism, and/or low RAIU. Subacute thyroiditis was diagnosed in patients with fever, neck pain or swelling, in the presence of elevated free T4 and free T3 levels, low thyroid gland echogenity, and/or low RAIU. OUTCOME MEASURES The main outcome measures were thyroid blood flow, thyroid volume, TBII status, and RAIU. RESULTS The study assessed 56 patients with Graves' disease (mean age 41.3 years), 28 patients with painless thyroiditis (mean age 40.9 years), 30 patients with subacute thyroiditis (mean age 50.0 years), and 25 healthy controls (mean age 38.7 years). Thyroid volume was greater in patients with thyroiditis than in healthy controls (P<0.0001); however, there was no significant difference in this parameter between the thyroiditis groups. Thyroid blood flow, TBII levels, and RAIU were higher in patients with Graves' disease than in those with destruction-induced thyrotoxicosis (P<0.0001). Patients with Graves' disease had a thyroid blood flow >4%, whereas patients with destruction-induced thyrotoxicosis had a thyroid blood flow <4%. All 56 patients with Graves' disease had TBII levels >15%. High TBII levels were also detected in 3 patients with painless thyroiditis and 1 patient with subacute thyroiditis. Thyroid blood flow correlated with RAIU at 3 h (coefficient of correlation [r] = 0.492; P <0.01) and 24h (r=0.762; P<0.001) in patients with Graves' disease and painless thyroiditis. There was no correlation, however, between thyroid blood flow and either thyroid volume or TBII level in patients with Graves' disease. CONCLUSION Thyroid blood flow >4% differentiated Graves' disease from destruction-induced thyrotoxicosis and was a reliable alternative to RAIU. [ABSTRACT FROM AUTHOR]

Abstract: It has been hypothesized that interferon (IFN) alpha and beta cause autoimmune thyroid dysfunctions by changing the Th1/Th2 balance, but the mechanisms involved are not yet known. The aims of this study were: (a) to test the effect of IFNalpha, IFNbeta and IFNgamma on the secretion of the Th1 chemokines CXCL9 and CXCL10, in “primary cultures of human thyroid follicular cells” (TFC); (b) to assess the effect of PPARgamma activation on CXCL9 and CXCL10 secretion. In TFC, CXCL9 and CXCL10 were undetectable in the supernatant. IFNgamma, IFNalpha and IFNbeta, dose dependently induced CXCL9 and CXCL10 release. TNFalpha alone had no effect. The combination of each of the IFNs with TNFalpha had a significant synergistic effect on CXCL9 and CXCL10 secretion. Treatment of TFC with rosiglitazone dose dependently inhibited the IFNs-stimulated CXCL9 and CXCL10 release. Compared with IFNalpha and IFNbeta, IFNgamma was the most potent stimulus of CXCL9 and CXCL10 secretion. In conclusion, IFNalpha, IFNbeta, IFNgamma and TNFalpha (synergistically with IFNs) dose-dependently induce the release of CXCL9 and CXCL10 by TFC, suggesting that this process may be related, at least in part, to the appearance of thyroid dysfunction during IFNs therapy. Furthermore, PPARgamma activation partially inhibits this process. [Copyright &y& Elsevier]