Body mass index is a good predictor of metabolic abnormalities in polycystic ovary syndrome.

AIM: To assess which parameters among hyperandrogenism (total testosterone-tT-or free androgen index-FAI), sex hormone binding globulin (SHBG) or body mass index (BMI) could better predict a worse metabolic profile in women with polycystic ovary syndrome (PCOS). METHODS: Five hundred and eighty-six women with PCOS and clinical or biochemical hyperandrogenism were included. Receiver Operating Characteristics (ROC) curves with tT, FAI, SHBG and BMI were performed for metabolic parameters and a cut-off with sensitivity and specificity was obtained for each parameter. The women were then divided into three groups and compared according to their BMI. RESULTS: Based on the ROC curves, tT proved not to be a good predictor of metabolic alterations. FAI and SHBG resulted to be good predictors of some markers of metabolic damage. The area under the curves (AUC) of SHBG were greater than those of FAI. SHBG levels affects the values of homeostasis model assessment of insulin resistance (HOMA-IR), fasting insulin, high density lipoproteins (HDL), low density lipoproteins (LDL), and total cholesterol also when corrected for BMI. However, the highest AUCs of the ROC curves were observed when BMI was used, which was significantly related to all the metabolic parameters analyzed. Dividing women according to their BMI, BMI between 25.00 and 30.00 kg/m2 had a worse metabolic profile but still in a normal range, while BMI ≥ 30 kg/m2 women had a significant metabolic derangement. DISCUSSION: BMI is a good predictor factor of metabolic changes in PCOS women at any age, and obesity is associated to the appearance of metabolic complications. Overweight and obese PCOS women should be addressed to perform a complete metabolic assessment.

Gene expression profile in functioning and non-functioning nodules of autonomous multinodular goiter from an area of iodine deficiency: unexpected common characteristics between the two entities.

PURPOSE: Toxic multinodular goiter is a heterogeneous disease associated with hyperthyroidism frequently detected in areas with deficient iodine intake, and functioning and non-functioning nodules, characterized by increased proliferation but opposite functional activity, may coexist in the same gland. To understand the distinct molecular pathology of each entity present in the same gland, the gene expression profile was evaluated by using the Affymetrix technology. METHODS: Total RNA was extracted from nodular and healthy tissues of two patients and double-strand cDNA was synthesized. Biotinylated cRNA was obtained and, after chemical fragmentation, was hybridized on U133A and B arrays. Each array was stained and the acquired images were analyzed to obtain the expression levels of the transcripts. Both functioning and non-functioning nodules were compared versus healthy tissue of the corresponding patient. RESULTS: About 16% of genes were modulated in functioning nodules, while in non-functioning nodules only 9% of genes were modulated with respect to the healthy tissue. In functioning nodules of both patients and up-regulation of cyclin D1 and cyclin-dependent kinase inhibitor 1 was observed, suggesting the presence of a possible feedback control of proliferation. Complement components C1s, C7 and C3 were down-regulated in both types of nodules, suggesting a silencing of the innate immune response. Cellular fibronectin precursor was up-regulated in both functioning nodules suggesting a possible increase of endothelial cells. Finally, Frizzled-1 was down-regulated only in functioning nodules, suggesting a role of Wnt signaling pathway in the proliferation and differentiation of these tumors. None of the thyroid-specific gene was deregulated in microarray analysis. CONCLUSION: In conclusion, the main finding from our data is a similar modulation for both kinds of nodules in genes possibly implicated in thyroid growth.

Screening for drugs potentially interfering with MCT8-mediated T3 transport in vitro identifies dexamethasone and some commonly used drugs as inhibitors of MCT8 activity.

BACKGROUND: Monocarboxylate transporter 8 (MCT8) is the first thyroid hormone transporter that has been linked to a human disease. Besides genetic alterations other factors might impair MCT8 activity. AIM: This study aimed at investigating whether some common drugs having a structural similarity with TH and/or whose treatment is associated with thyroid function test abnormalities, or which behave as antagonists of TH action can inhibit MCT8-mediated T3 transport. METHODS: [125I]T3 uptake and efflux were measured in COS-7 cells transiently transfected with hMCT8 before and after exposure to increasing concentrations of hydrocortisone, dexamethasone, prednisone, prednisolone, amiodarone, desethylamiodarone, dronedarone, buspirone, carbamazepine, valproic acid, and L-carnitine. The mode of inhibition was also determined. RESULTS: Dexamethasone significantly inhibited T3 uptake at 10 µM; hydrocortisone reduced T3 uptake only at high concentrations, i.e. at 500 and 1000 µM; prednisone and prednisolone were devoid of inhibitory potential. Amiodarone caused a reduction of T3 uptake by MCT8 only at the highest concentrations used (44% at 50 µM and 68% at 100 µM), and this effect was weaker than that produced by desethylamiodarone and dronedarone; buspirone resulted a potent inhibitor, reducing T3 uptake at 0.1-10 µM. L-Carnitine inhibited T3 uptake only at 500 mM and 1 M. Kinetic experiments revealed a noncompetitive mode of inhibition for all compounds. All drugs inhibiting T3 uptake did not affect T3 release. CONCLUSION: This study shows a novel effect of some common drugs, which is inhibition of T3 transport mediated by MCT8. Specifically, dexamethasone, buspirone, desethylamiodarone, and dronedarone behave as potent inhibitors of MCT8.

Effect of aging on clinical features and metabolic complications of women with polycystic ovary syndrome.

PURPOSE: To assess the distribution of clinical features and metabolic abnormalities of polycystic ovary syndrome (PCOS) women according to their age. METHODS: Retrospective study on 602 women (mean age 23.9 ± 6.2 years), diagnosed according to International PCOS Network Guidelines criteria as having PCOS in a University-based Hospital. Anthropometric features, hormonal and metabolic parameters were measured and compared between the different age groups (group A ≤ 20 years; group B 21-30 years; group C > 30 years). RESULTS: Patients in group A were more often hyperandrogenic, while in group C hypertension, dyslipidemia, obesity, impaired fasting glucose, and insulin resistance (IR) were more prevalent. After adjusting for BMI, age correlated positively with sex hormone-binding globulin (SHBG), IR, total- and LDL-cholesterol, and negatively with DHEAS, insulin, and free androgen index (FAI). SHBG was significantly associated with IR and atherogenic dyslipidemia, while FAI levels were linked to hypertension, independently of other factors considered. Furthermore, the regression analysis showed a stronger relationship between BMI and metabolic outcomes, regardless of age. CONCLUSION: Polycystic ovarian syndrome (PCOS) phenotype changes with age. Clinical and biochemical hyperandrogenism are a major concern in young PCOS women, while metabolic burden tends to increase with aging. Some of the cardiovascular risk factors are dependent on FAI and SHBG levels, whereas BMI confirms its key role in the genesis of most of the metabolic sequelae in PCOS, independently of age.

Genetic interaction analysis of VEGF-A rs3025039 and VEGFR-2 rs2071559 identifies a genetic profile at higher risk to develop nodular goiter.

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.

Treatment of Graves' hyperthyroidism with thionamides: a position paper on indications and safety in pregnancy.

CONTEXT: Graves' disease affects 3% of women and 0.5% of men in the general population. The first line treatment of Graves' hyperthyroidism is based on the administration of antithyroid drugs (ATD), propylthiouracil (PTU), methimazole (MMI) and carbimazole. A recent warning from the Italian Drug Agency (Agenzia Italiana del Farmaco AIFA) reported the risk of MMI-induced acute pancreatitis. In addition, AIFA highlighted the possible association of MMI treatment during the first trimester of pregnancy with congenital malformations, thus recommending the use of effective contraceptive methods in women of childbearing age treated with MMI. METHODS AND RESULTS: Revision of literature reported less than ten cases of the alleged MMI pancreatitis, allowing the inclusion of MMI in class III drug regarding the relative risk for drug-induced pancreatitis. Data available on the effect of hyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman. Case reports and population studies either suggesting or not suggesting MMI-induced fetal malformations do not allow unquestionable conclusions on this matter. CONCLUSIONS: This consensus by experts from Italian Endocrine and Gynecologic Scientific Societies has edited recommendations derived form the available data and published guidelines of International Scientific Societies.

Effect of long- and short-chain perfluorinated compounds on cultured thyroid cells viability and response to TSH.

PURPOSE: Perfluorinated chemicals are widespread pollutants persistent in the environment with links to some major health issues. The two main compounds, perfluoro-octanoic acid (PFOA) and perfluoro-alkyl sulphonate (PFOS), were recently classified as carcinogenetic and thus their use has been restricted. Short-chain PFCs were recently developed as an alternative, but no data regarding the possible endocrine toxicities of these compounds are available. Aim of this study was to investigate whether short-chain PFCs could jeopardize thyroid cell viability and/or interfere with the functional effect TSH. METHODS: Fisher rat thyroid line-5 (FRTL-5) was treated with increasing concentrations of PFOA, PFOS, perfluorobutanesulfonic acid (PFBS), perfluorobutanoic acid (PFBA), pentafluoropropionic anhydride (PFPA), perfluoropentanoic acid (PFPeA) to evaluate modifications in cell viability and TSH-stimulated cAMP production. RESULTS: Neither long nor short-chain PFCs affected cell viability (apart from PFOS 100 µM), or interfered with cAMP production. CONCLUSIONS: The results of the present study demonstrate for the first time that short-chain PFCs have no acute cytotoxic effect on thyroid cells in vitro and that cAMP production is not modulated by any of the tested PFCs.

Pregnancy outcome in women treated with methimazole or propylthiouracil during pregnancy.

PURPOSE: Control of thyroid function in hyperthyroid women during pregnancy is based on antithyroid drugs (ATD) [propylthiouracil (PTU) and methimazole (MMI)]. While a teratogenic effect has been suggested for MMI and, more recently, for PTU, a clear demonstration is still lacking. Aim of this study was to assess the safety of ATD during pregnancy. METHODS: A total of 379 pregnancies were retrospectively recruited in eight Italian Departments of Endocrinology and divided in five groups: (1) MMI-treated and euthyroid throughout pregnancy (n = 89); (2) MMI-treated and hyperthyroid on at least two occasions (n = 35); (3) PTU-treated women and euthyroid throughout pregnancy (n = 32); (4) PTU-treated women and hyperthyroid on at least two occasions (n = 20); and (5) non-ATD-treated (n = 203). Data on maternal thyroid function, miscarriages, type of delivery, neonatal weight, length and TSH, perinatal complications and congenital malformation were analyzed. RESULTS: The gestational age at delivery, the rate of vaginal delivery, neonatal weight, length and neonatal TSH did not significantly differ among groups. In all groups, the rates of spontaneous miscarriage and of major congenital malformations were not higher than in the general population. No newborns were born with a phenotype similar to those described in the "MMI embryopathy". CONCLUSIONS: While a clear demonstration of a teratogenic effect of MMI is currently lacking, it seems reasonable to follow the current guidelines and advice for PTU treatment in hyperthyroid women during the first trimester of pregnancy. Further, large and prospective worldwide studies will be needed to fully clarify the issue of ATD safety during pregnancy.

Rare diseases in clinical endocrinology: a taxonomic classification system.

PURPOSE: Rare endocrine-metabolic diseases (REMD) represent an important area in the field of medicine and pharmacology. The rare diseases of interest to endocrinologists involve all fields of endocrinology, including rare diseases of the pituitary, thyroid and adrenal glands, paraganglia, ovary and testis, disorders of bone and mineral metabolism, energy and lipid metabolism, water metabolism, and syndromes with possible involvement of multiple endocrine glands, and neuroendocrine tumors. Taking advantage of the constitution of a study group on REMD within the Italian Society of Endocrinology, consisting of basic and clinical scientists, a document on the taxonomy of REMD has been produced. METHODS AND RESULTS: This document has been designed to include mainly REMD manifesting or persisting into adulthood. The taxonomy of REMD of the adult comprises a total of 166 main disorders, 338 including all variants and subtypes, described into 11 tables. CONCLUSIONS: This report provides a complete taxonomy to classify REMD of the adult. In the future, the creation of registries of rare endocrine diseases to collect data on cohorts of patients and the development of common and standardized diagnostic and therapeutic pathways for each rare endocrine disease is advisable. This will help planning and performing intervention studies in larger groups of patients to prove the efficacy, effectiveness, and safety of a specific treatment.

BRAF mutation analysis in thyroid nodules with indeterminate cytology: our experience on surgical management of patients with thyroid nodules from an area of borderline iodine deficiency.

PURPOSE: Fine-needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains indeterminate for 12-18 % of nodules. BRAF V600E mutation has been reported to show a high specificity for malignant thyroid nodules and the use of this marker to refine indeterminate FNA cytology results may be a useful diagnostic adjunctive tool in the pre-operative evaluation of thyroid nodules. The aim of this study was to estimate the prevalence of BRAF exon 15 mutation (V600E) and its clinical value as a diagnostic tool in a series of thyroid nodules with indeterminate cytology from an area of borderline iodine deficiency. SUBJECTS AND METHODS: One hundred and fifty-three thyroid samples obtained by FNA of thyroid nodules from 151 patients were subjected to the analysis of BRAF V600E mutation by direct sequencing. In the study 54 nodules with indeterminate cytology, 56 benign and 43 malignant thyroid nodules were included. RESULTS: V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules and in only 1/54 indeterminate nodules that, after histology, turned out to be at a papillary thyroid carcinoma. CONCLUSIONS: The application of BRAF exon 15 analysis showed limitations when applied to discriminate thyroid nodules with indeterminate cytology if wild-type BRAF is found, and there is no role for avoiding diagnostic thyroid surgery.

Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies.

The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine ((131)I) treatment for Graves' disease (GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before (131) I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay (ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to (125-) (I) Tg by a pool of four TgAb-Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb-Fab. Total TgAb immunoglobulin (Ig)G rose significantly (P = 0.024). TgAb κ chains did not change (P = 0.052), whereas TgAb λ chains increased significantly (P = 0.001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after (131)I (P = 0.008 and P = 0.006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb-Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb-Fab A was observed 3 and 6 months after (131)I. We conclude that (131)I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern.

Frequency and effect on serum TSH of phosphodiesterase 8B (PDE8B) gene polymorphisms in patients with sporadic nonautoimmune subclinical hypothyroidism.

BACKGROUND: Nonautoimmune subclinical hypothyroidism (NSH) is characterized by elevated serum TSH in presence of normal thyroid hormone levels and absence of anti-thyroid antibodies. As result of a genomic-wide study, a strong association between three polymorphic variants in intron 1 of human PDE8B gene (rs4704397, rs6885099, rs2046045) and serum TSH has been reported in euthyroid subjects. AIM: The aim of this study was to evaluate frequency and effects on serum TSH of PDE8B gene polymorphisms in patients with sporadic NSH and verify if differences in serum TSH levels are associated to these polymorphic variants. SUBJECTS AND METHODS: A total of 58 Italian selected patients affected by NSH, with elevated serum TSH, normal FT3 and FT4 and without TSHr gene mutations, were subjected to genotyping for specific single nucleotide polymorphism of PDE8B gene. RESULTS: In all patients, the integrity of TSH receptor gene was attested. The ancestral allele associated with increased serum TSH was present in 42/58 patients (72.4 %) for rs4704397, in 42/58 patients (72.4 %) for rs6885099 and in 44/58 patients (75.9 %) for rs2046045. However, similar values of serum TSH were detected in patients with minor or major allele for each polymorphism. CONCLUSIONS: A prevalence of the minor allele of PDE8B gene polymorphism associated with elevated serum levels of TSH was demonstrated in patients affected by sporadic NSH; however, significant differences in circulating TSH in patients with minor or major alleles for each polymorphism were not identified demonstrating the lack of association between the polymorphisms and serum TSH levels in these patients.

Thyroid and menopause.

Thyroid dysfunction is common in the general population especially in women. All thyroid diseases are in fact more common in women than in men and may interfere with the reproductive system. Thyroid function and the gonadal axes are related throughout the woman's fertile period. The relationship between the two glands is mutual. In particular, thyroid hormones affect the reproductive function both directly and indirectly through several actions. Studies on the relationship between menopause and thyroid function are few and do not allow to clarify whether menopause has an effect on the thyroid regardless of aging. With aging, the main changes regarding thyroid physiology and function are: a reduction of thyroid iodine uptake, free thyroxine and free triiodothyronine synthesis and catabolism of free thyroxine while reverse triiodothyronine increases; the level of thyroid stimulating hormone remains normal with sometimes a tendency to higher limits. These changes are present in both sexes without distinction between males and females. The complexity of the relationships can be summarized in three aspects: thyroid status does not influence significantly the climacteric syndrome; menopause may modify the clinical expression of some thyroid diseases, particularly the autoimmune ones; thyroid function is not directly involved in the pathogenesis of the complications of menopause. However, coronary atherosclerosis and osteoporosis may be aggravated in the presence of hyperthyroidism or hypothyroidism. The effects of postmenopausal estrogen replacement on thyroxine requirements in women with hypothyroidism should be considered.

The W520X mutation in the TSHR gene brings on subclinical hypothyroidism through an haploinsufficiency mechanism.

BACKGROUND: TSHR is a G-protein-coupled seven transmembrane domain receptor that activates the two major signal transduction pathways: the Gαs/adenylate cyclase and the Gαq/11/phospholipase C pathways. Inactivating mutations in the TSHR gene have been demonstrated to be responsible for subclinical hypothyroidism, a disorder characterized by elevated serum TSH concentrations despite normal thyroid hormones levels. AIM: We identified in a child a nonsense mutation (W520X) in the third transmembrane domain of the TSHR that causes the lack of the C-terminus portion of the receptor. The functional significance of this variation was assessed in vitro. MATERIAL/SUBJECT AND METHODS: The W520X mutation was introduced into the pSVL vector containing the wild-type sequence of TSHR gene. Wild-type and mutated vectors were expressed in Chinese Hamster Ovary (CHO) cells, and cAMP, inositol phosphate (IP), immunofluorescence and FACS analyses were performed. RESULTS: Transfection with pSVL-TSHR vector induced basal cAMP and IP production in the absence of TSH stimulation, indicating a constitutive activity for the TSHR. An impairment of receptor function was demonstrated by the observation that cells expressing the mutant TSHR exhibited a lower second messenger production with respect to the wild-type, despite a normal expression of the receptor at the cell surface. CONCLUSIONS: The mechanism through which the W520X mutation exerts its effect is more likely haploinsufficiency rather than a dominant-negative effect. This could explain the phenotype of our patient, who has a hormonal pattern in the range of a mild subclinical hypothyroidism, without an overt disease phenotype.

The effect of voluntary iodine prophylaxis in a small rural community: the Pescopagano survey 15 years later.

CONTEXT: Iodine deficiency disorders are a major public health problem, and programs have been implemented to improve iodine nutrition. OBJECTIVE: The objective of the study was to verify the effects of voluntary iodine prophylaxis in a small rural community (Pescopagano, Italy). DESIGN: The design of the study was the evaluation of the prevalence of thyroid disorders 15 years after a previous survey conducted before iodine prophylaxis. SETTING: The setting for this study was a general community survey. PARTICIPANTS: One thousand one hundred forty-eight residents were examined in 2010 and 1411 in 1995. RESULTS: In 2010, 757 of 1148 subjects (65.9%) routinely used iodized salt, urinary iodine excretion being significantly higher than in 1955 (median 98.0 µg/L, vs 55.0 µg/L, P < .0001). The prevalence of goiter was lower in 2010 than in 1995 (25.8% vs 46.1%, P < .0001), mainly due to the reduction of diffuse goiter (10.3% vs 34.0%, P < .0001). In 2010 vs 1995, thyroid autonomy in subjects younger than 45 years old (3 of 579, 0.5% vs 25 of 1010, 2.5% P = .004) and nonautoimmune hyperthyroidism in subjects older than 45 years old (8 of 569, 1.4% vs 18 of 401, 4.5%, P = .03) were less frequent. The prevalence of hypothyroidism was higher in 2010 vs 1995 (5.0% vs 2.8%, P = .005), mainly because of an increased frequency of subclinical hypothyroidism in subjects younger than 15 years old (7 of 83, 8.4% vs 0 of 419, 0.0%, P < .0001). Accordingly, serum thyroid autoantibodies (19.5% vs 12.6%; P < .0001) and Hashimoto's thyroiditis (14.5% vs 3.5%; P < .0001) were more frequent in 2010 than in 1995. CONCLUSIONS: In the present work, the role of voluntary iodine prophylaxis was assessed in a small rural community relatively segregated, in which genetic and other environmental factors have not substantially changed between the 2 surveys. Iodine intake strongly affected the pattern of thyroid diseases, but the benefits of correcting iodine deficiency (decreased prevalence of goiter and thyroid autonomy in younger subjects and reduced frequency of nonautoimmune hyperthyroidism in older subjects) far outweighs the risk of development of thyroid autoimmunity and mild hypothyroidism in youngsters.

The Italian screening program for primary congenital hypothyroidism: actions to improve screening, diagnosis, follow-up, and surveillance.

The Italian screening program for primary congenital hypothyroidism (CH) is an integrated system including neonatal screening, diagnosis, treatment, follow-up, and nationwide surveillance of the disease. The aim of the Italian screening program for CH is to identify not only babies with severe permanent CH (core target), but also babies with mild persistent and transient forms of CH who could have a benefit from an early replacement therapy (secondary target). In the last years, despite the important results obtained in terms of standardization of screening and follow-up procedures, it has become clear the need of optimizing the program in order to harmonize the screening strategy and the screening procedures among Regions, and to improve the diagnostic and therapeutic approach in all affected infants. On the basis of available guidelines, the experience of the Italian screening and clinical reference centers, and the knowledge derived from the nation-wide surveillance activity performed by the Italian National Registry of Infants with CH, the Italian Society for Pediatric Endocrinology and Diabetology together with the Italian Society for the Study of Metabolic Diseases and Neonatal Screening and the Italian National Institute of Health promoted actions aimed at improving diagnosis, treatment, follow-up and surveillance of CH in our country. In this paper the most important actions to improve the Italian screening program for CH are described.

In vivo assessment about the effects of a diet containing iodine-enriched foodstuffs. A pilot study in 30 volunteers.

BACKGROUND: Iodine deficiency (ID) still now represents one of the major worldwide health problems. ID is the result of insufficient dietary iodine intake. Iodine is an essential micronutrient but scarcely present in nature. The main strategy for the correction of ID is the fortification of table salt with iodide/iodine but Italy is far from reaching an iodized salt use higher 90% of population. Also because of the evidence for the risk on blood pressure, it is recommended to decrease the daily salt intake to less than 5 g/d. An opportunity to increase the iodine intake is the possibility to introduce iodine fortification in the industrial processing of foods. AIM: The aim was to evaluate the effectiveness of a diet containing iodized foods enriched during industry processing with protected iodized salt (Presal®). SUBJECTS AND METHODS: The evaluation of increasing of iodine intake was assessed by measuring the urinary iodine excretion (UIE) in 30 healthy volunteers who added to their alimentary habits a basket of iodine-enriched foodstuffs. RESULTS: Median UIE at baseline was 105 µg/l, 156 µg/l during the enriched diet and 90.5 µg/l a week after withdrawal of enriched diet. CONCLUSIONS: Stable iodized salt (Presal®) represents a good way to introduce iodine with the normal diet without increasing the normal consumption of salt for the healthy problems related to the blood pressure. The availability of stable iodized salt (Presal®) allows the preservation of iodine after cooking.

Genetic markers to discriminate benign and malignant thyroid nodules with undetermined cytology in an area of borderline iodine deficiency.

BACKGROUND: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. AIM: We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. SUBJECTS AND METHODS: The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. RESULTS: A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. CONCLUSIONS: The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.

Thyroid autoimmunity may represent a predisposition for the development of fibromyalgia?

In our previous study, we observed that the presence of autoimmune thyroid disease worsens fibromyalgia (FM) symptoms. The aims of this study are to evaluate whether there is a predisposition for the development of FM in patients with Hashimoto's thyroiditis (HT) with or without subclinical hypothyroidism (SCH) and in patients with SCH alone and what is the weight of antithyroid antibody positivity and SCH on FM comorbidity. Fifty-two patients, 39 affected by HT with or without SCH and 13 by SCH, were matched with 37 patients affected by FM and 25 healthy subjects. Blood samples were collected from all study subjects for the determination of serum TSH, free triiodothyronine, free thyroxine, antithyroperoxidase antibody (TPOAb), antithyroglobulin antibody (TgAb) and non-organ-specific autoantibodies. Clinical assessment of patients and controls included the "Fibromyalgia Impact Questionnaire" (FIQ), while pain severity was evaluated using a visual analogue scale (VAS). Patients and controls were also characterized by the presence of diffuse pain, fatigue, paresthesiae, muscle spasms, non-restful sleep, tension headache and presence of mood disorders. FM comorbidity resulted in twelve HT subjects (31%) and none in SCH patient. In particular, FM comorbidity in HT patients without SCH was 33.3% and in HT patients with SCH was 28.5%. Based on our data, we speculate that maybe there is more than a hypothesis regarding the cause-effect relation between thyroid autoimmunity and the presence of FM, thus suggesting a hypothetical role of thyroid autoimmunity in FM pathogenesis.