Fifteen Years of Iodine Prophylaxis in Italy: Results of a Nationwide Surveillance (Period 2015-2019).

CONTEXT: In 2005, a nationwide program of iodine prophylaxis on a voluntary basis was implemented in Italy by law. However, recent data on iodine status are lacking. OBJECTIVE: The aim of this study was to evaluate efficiency, effectiveness, and possible adverse effects (increased occurrence of thyroid autoimmunity and hyperthyroidism) of the Italian iodine prophylaxis program. METHODS: From 2015 to 2019, a nationwide survey was performed. The use of iodized salt was evaluated in a sample of 164 593 adults and in 998 school canteens. A sample of 4233 schoolchildren (aged 11-13 years) was recruited to assess urinary iodine concentration, prevalence of goiter, and thyroid hypoechogenicity on ultrasound, with the latter being an indirect indicator of thyroid autoimmunity. Neonatal TSH values of 197 677 infants screened in regions representative of Northern, Central, and Southern Italy were analyzed to investigate the percentage of TSH values >5.0 mIU/L. Data on methimazole prescriptions were analyzed as indirect indicators of new cases of hyperthyroidism. RESULTS: The prevalence of the use of iodized salt was 71.5% in adult population and 78% in school canteens. A median urinary iodine concentration of 124 µg/L, a prevalence of goiter of 2.2%, and a prevalence of thyroid hypoechogenicity of 5.7% were observed in schoolchildren. The percentage of neonatal TSH values >5.0 mIU/L resulted still higher (5.1%) than the World Health Organization threshold of 3.0%, whereas the prescriptions of methimazole showed a reduction of 13.5%. CONCLUSION: Fifteen years of iodine prophylaxis have led to iodine sufficiency in Italy, although there still is concern about iodine nutritional status during pregnancy.

Obesity and Monitoring Iodine Nutritional Status in Schoolchildren: is Body Mass Index a Factor to Consider?

Background: The frequency of overweight (OW) and obese (OB) children has increased worldwide, particularly in economically developed countries. No studies have been conducted to verify whether the increasing frequency of OW and obesity in schoolchildren may affect the evaluation of iodine nutritional status in populations. The aim of this study was to verify whether urinary iodine concentration (UIC), thyroid volume (TV), and thyroid hypoechoic pattern may be affected by body mass index (BMI) in schoolchildren. Methods: The children included in this study (aged 11-13 years) were a part of the schoolchildren recruited in the second nationwide survey (period 2015-2019) conducted in Italy to monitor by law (Atto di Intesa Stato-Regioni February 26, 2009) the nationwide iodine prophylaxis program. Specifically, 1281 schoolchildren residing in iodine-sufficient areas (IS group) and 384 children residing in a still mildly iodine-deficient area (ID group) were recruited between January and March 2015 in the first-degree secondary state schools. In all the children, spot UIC was measured, thyroid ultrasound was performed to evaluate TV, and hypoechogenicity was assessed to indirectly evaluate iodine-associated thyroid autoimmunity. Results: The frequency of OW, OB, and adequate weight (AW) children was similar in the IS and ID groups at any age. After adjusting for sex and age, the regression analysis showed lower UIC values in OB children than in AW children of the IS group (beta coefficient = -34.09 [95% confidence interval -65.3 to -2.8]), whereas no significant differences were observed in the ID group. In both the IS and ID groups, the distribution of TV in AW children was significantly shifted toward lower values in comparison to the distribution of OB children (p < 0.001 in the IS group; p = 0.012 in the ID group). Furthermore, the frequency of thyroid hypoechogenicity was higher in the ID group than in the IS group (10.9% vs. 6.6%, p = 0.005); however, in both groups, it was significantly lower in AW children than in OB children (p < 0.01). Conclusions: This study for the first time demonstrates that BMI may be a confounding factor in monitoring iodine nutritional status in schoolchildren. Since in Italy as in other Western countries the number of OW and OB children is high, BMI is a factor to consider in monitoring salt iodization programs worldwide.

A functional soluble form of CTLA-4 is present in the serum of celiac patients and correlates with mucosal injury.

Celiac disease (CD) is a multifactorial disorder influenced by environmental, genetic and immunological factors. Increasing evidence showed CTLA-4 gene as an important susceptibility locus for autoimmune disorders. A native soluble cytotoxic T-lymphocyte-associated protein-4 (sCTLA-4), lacking of transmembrane sequence, has been described in several autoimmune diseases. We aimed to evaluate the presence of increased sCTLA-4 concentration in the serum of patients with CD and the possible immunoregulatory function. Blood samples were collected from 160 CD patients; sCTLA-4 levels were evaluated by ELISA, western blot and reverse transcription-PCR. The capability of serum sCTLA-4 to modulate T-lymphocyte proliferation in vitro was evaluated by two-way mixed leukocyte reaction assay. We demonstrated high levels of sCTLA-4 in serum of untreated celiac patients. Additionally, we observed that sCTLA-4 concentrations are related to gluten intake and that a correlation between autoantibodies to tissue transglutaminase and sCTLA-4 concentration exists. Moreover, sCTLA-4 levels correlate with the degree of mucosal damage. Conversely, no correlation between sCTLA4 levels and the HLA-related risk was observed. Finally, we show that sCTLA-4 from sera of CD patients displays functional activities. These results strongly suggest a regulation of sCTLA-4 synthesis depending on the presence or absence of dietary gluten and imply a possible immunomodulatory effect on cytotoxic T lymphocyte functions. In gluten-exposed patients, serum sCTLA-4 levels might provide insight about mucosal injury.

Clinical efficacy of radioiodine therapy in multinodular toxic goiter, applying an implemented dose calculation algorithm.

Radioiodine is a common therapeutic option for Multinodular Toxic Goiter (MTG). We evaluated an algorithm for personalized radioiodine activity calculation. Ninety-three (28 male, 65 female; 43-84 years) patients with MTG eligible for radioiodine treatment (131I-iodide) were studied. The quantity of 131I-iodide to be administered was estimated by Thyroid Volume Reduction (TVR) algorithm, developed for Graves' disease. It takes into account 131I uptake, its effective half-life (T1/2eff), thyroid volume, and its expected reduction during treatment. A comparison with the activity calculated by other dosimetric protocols and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid volume by ultrasonography (US), thyroid stimulating hormone (TSH), and thyroid hormones by standard immunometric methods. In a follow-up of 6-120 months, remission of hyperthyroidism after a single 131I-iodide treatment was observed in 76 patients (64 euthyroid, 12 hypothyroid). The thyroid volume reduction observed by US after the treatment fairly correlated with what predicted by our model; T1/2eff was highly variable and critically affected dose calculation. The administered activities (median 526 MBq, range 156-625 MBq) were slightly lower than the "fixed" activities (600 MBq) and with respect to the other protocols' prescriptions (-15/38%); the median 131I activity administered to relapsed patients (605 MBq) was significantly greater (P=0.01) with respect to the dose administered to cured patients (471 MBq). Our study shows that an effective cure of MTG can be obtained with relatively low 131I activities and probably with a relatively low incidence of hypothyroidism, using TVR method.

Long-term outcome of low-activity radioiodine administration preceded by adjuvant recombinant human TSH pretreatment in elderly subjects with multinodular goiter.

BACKGROUND: Large multinodular goiter (MNG) in elderly people is a common finding which can require intervention. The long-term effect of radioiodine therapy on thyroid volume (TV) and function after recombinant human (rh) TSH pre-treatment was evaluated. METHODS: After baseline evaluation, 40 subjects over 60 years old with a large MNG were treated with 131I up to the activity of 600 MBq. Nineteen patients were pretreated with rhTSH (0.1 mg on 2 consecutive days; group 1) while 21 subjects underwent treatment without rhTSH pretreatment (group 2). TV was monitored every 6-12 months by ultrasonography. The median follow-up period was 36 months. RESULTS: At the baseline, the groups matched in terms of TV, 24-h radioiodine uptake (RAIU), urinary iodine and neck complaints. The number of subjects pretreated with anti-thyroid drugs was significantly (P = 0.01) greater in group 2 than in group 1; TSH was more suppressed (P = 0.003) and f-T3 was more elevated (P = 0.005) in group 2 than in group 1 patients. RhTSH increased 24-h RAIU in group 1 up to the baseline level observed in group 2. The 131I activity administered was similar in both groups. Adverse events were slight and similar in both groups. A permanent post-radioiodine toxic condition was reported only in 2 patients in group 2. After radioiodine therapy, hypothyroidism was observed in significantly more group 1 patients than group 2 patients (P = 0.002). While TV was reduced in both groups, the percentage TV reduction recorded at the last examination was significantly higher (P = 0.03) in group 1 than in group 2. MNG-related complaints were significantly reduced in both group 1 (P = 0.0001 vs baseline) and group 2 (P = 0.001) patients. CONCLUSION: Low radioiodine activities after pretreatment with low-dosage rhTSH are able to reduce TV and improve MNG-related symptoms in elderly subjects.