Differentiated thyroid cancer in children: Heterogeneity of predictive risk factors.

OBJECTIVE: To correlate clinical and pathological characteristics at diagnosis with patient long-term outcomes and to evaluate ongoing risk stratifications in a large series of paediatric differentiated thyroid cancers (DTC). STUDY DESIGN: Retrospective analysis of clinical and pathological prognostic factors of 124 paediatric patients with DTC (age at diagnosis <19 years) followed up for 10.4 ± 8.4 years. Patients with a follow-up >3 years (n = 104) were re-classified 18 months after surgery on the basis of their response to therapy (ongoing risk stratification). RESULTS: Most patients had a papillary histotype (96.0%), were older than 15 years (75.0%) and were diagnosed because of clinical local symptoms (63.7%). Persistent/recurrent disease was present in 31.5% of cases during follow-up, but at the last evaluation, only 12.9% had biochemical or structural disease. The presence of metastases in the lymph nodes of the lateral compartment (OR 3.2, 95% CI, 1.28-7.16, P = 0.01) was the only independent factor associated with recurrent/persistent disease during follow-up. At the last evaluation, biochemical/structural disease was associated with node metastases (N1a, N1b) by univariate but not multivariate analysis. Ongoing risk stratification compared to the initial risk classification method better identified patients with a lower probability of persistent/recurrent disease (NPV = 100%). CONCLUSIONS: In spite of the aggressive presentations at diagnosis, paediatric patients with DTC show an excellent response to treatment and often a favourable outcome. N1b status should be considered a strong predictor of persistent/recurrent disease which, as in adults, is better predicted by ongoing risk stratification.

Thyroid physiology in pregnancy.

OBJECTIVE: Various physiological changes occur in maternal thyroid economy during pregnancy. This review focuses on the events taking place during gestation that together strongly influence maternal thyroid function. METHODS: Scientific reports on maternal thyroid physiology in pregnancy. RESULTS: During the 1st trimester, human chorionic gonadotropin (hCG) induces a transient increase in free thyroxine (FT4) levels, which is mirrored by a lowering of thyroid-stimulating hormone (TSH) concentrations. Following this period, serum FT4 concentrations decrease of approximately 10 to 15%, and serum TSH values steadily return to normal. Also starting in early gestation, there is a marked increase in serum thyroxine-binding globulin (TBG) concentrations, which peak around midgestation and are maintained thereafter. This event, in turn, is responsible for a significant rise in total T4 and triiodothyronine (T3). Finally, significant modifications in the peripheral metabolism of maternal thyroid hormones occur, due to the expression and activity of placental types 2 and 3 iodothyronine deiodinases (D2 and D3, respectively). CONCLUSION: In line with these variations, both free thyroid hormone and TSH reference intervals change throughout pregnancy, and most scientific societies now recommend that method- and gestation-specific reference ranges be used for interpreting results in pregnancy.The maternal iodide pool reduces during pregnancy because of increased renal clearance of iodine and transfer of iodine to the feto-placental unit. This results in an additional requirement of iodine during pregnancy of ~100% as compared to nonpregnant adults. In accordance, the recommended iodine intake in pregnancy is 250 µg/day. A daily iodine intake below this threshold poses risks of various degrees of thyroid insufficiency for both the mother and the fetus.

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.

Preconception Thyrotropin Levels and Thyroid Function at Early Gestation in Women With Hashimoto Thyroiditis.

CONTEXT: Preconception optimization of thyroid function in women with Hashimoto thyroiditis (HT) is highly recommended to prevent/reduce the risk of thyroid insufficiency at early gestation. OBJECTIVE: This work aimed to evaluate the prevalence of first-trimester thyroid insufficiency in HT women with preconception thyrotropin (T0-TSH) values consistently less than or equal to 2.5 mIU/L with or without levothyroxine (LT4) treatment, and to calculate T0-TSH cutoffs that best preconceptionally identified HT women requiring first-trimester LT4 adjustment/prescription. METHODS: Serum TSH was obtained at 4- to 6-week intervals from 260 HT pregnant women (122 on LT4 [Hypo-HT]; 138 euthyroid without LT4 [Eu-HT]), prospectively followed from preconception up to pregnancy term. Receiver operating characteristic (ROC) curves were plotted to identify T0-TSH cutoffs best predicting first-trimester TSH levels greater than 2.5 mIU/L (diagnostic criterion [DC] 1) and greater than 4.0 mIU/L (DC 2). RESULTS: At first trimester, TSH was greater than 2.5 mIU/L in approximately 30% of both Hypo-HT and Eu-HT women, and greater than 4.0 mIU/L in 19.7% Hypo-HT and 10.1% Eu-HT women (P = .038). The optimal ROC-based T0-TSH cutoffs found were 1.24 mIU/L/1.74 mIU/L in Hypo-HT, and 1.73 mIU/L/2.07 mIU/L in Eu-HT women, for DC 1 and DC 2, respectively. T0-TSH values exceeding these cutoffs resulted in a statistically significantly increased risk of first-trimester thyroid insufficiency (odds ratio [OR] [95% CI)] 15.92 [5.06-50.15] and 16.68 [5.13-54.24] in Hypo-HT; 16.14 [6.47-40.30] and 17.36 [4.30-70.08] in Eu-HT women, for DC 1 and DC 2, respectively). CONCLUSION: The preconception TSH cutoffs that guaranteed a first-trimester TSH less than 2.5 mU/L in hypothyroid- and euthyroid-HT women were, respectively, almost 50% (1.24 mU/L) and 30% (1.73 mU/L) lower than this gestational target, and 1.74 mU/L and 2.07 mU/L in hypothyroid- and euthyroid-HT women, respectively, for a gestational target of 4.0 mU/L.

Fish and the Thyroid: A Janus Bifrons Relationship Caused by Pollutants and the Omega-3 Polyunsaturated Fatty Acids.

Benefits of the omega-3 polyunsaturated fatty acids (PUFA) on a number of clinical disorders, including autoimmune diseases, are widely reported in the literature. One major dietary source of PUFA are fish, particularly the small oily fish, like anchovy, sardine, mackerel and others. Unfortunately, fish (particularly the large, top-predator fish like swordfish) are also a source of pollutants, including the heavy metals. One relevant heavy metal is mercury, a known environmental trigger of autoimmunity that is measurable inside the thyroid. There are a number of interactions between the omega-3 PUFA and thyroid hormones, even at the level of the thyroid hormone transport proteins. Concerning the mechanisms behind the protection from/amelioration of autoimmune diseases, including thyroiditis, that are caused by the omega-3 PUFA, one can be the decreased production of chemokines, a decrease that was reported in the literature for other nutraceuticals. Recent studies point also to the involvement of resolvins. The intracellular increase in resolvins is associated with the tissue protection from inflammation that was observed in experimental animals after coadministration of omega-3 PUFA and thyroid hormone. After having presented data on fish consumption at the beginning, we conclude our review by presenting data on the market of the dietary supplements/nutraceuticals. The global omega-3 products market was valued at USD 2.10 billion in 2020, and was projected to go up at a compound annual growth rate of 7.8% from 2020 to 2028. Among supplements, fish oils, which are derived mainly from anchovies, are considered the best and generally safest source of omega-3. Taking into account (i) the anti-autoimmunity and anti-cancer properties of the omega-3 PUFA, (ii) the increasing incidence of both autoimmune thyroiditis and thyroid cancer worldwide, (iii) the predisposing role for thyroid cancer exerted by autoimmune thyroiditis, and (iv) the risk for developing metabolic and cardiovascular disorders conferred by both elevated/trendwise elevated serum TSH levels and thyroid autoimmunity, then there is enough rationale for the omega-3 PUFA as measures to contrast the appearance and/or duration of Hashimoto's thyroiditis as well as to correct the slightly elevated serum TSH levels of subclinical hypothyroidism.

Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study.

OBJECTIVE: We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti-thyroid antibody-negative women from a mild-moderately iodine-deficient (ID) area. DESIGN: Observational cohort study. PATIENTS: The study included 168 women receiving prenatal preparations containing 150 µg of iodine from early pregnancy (150-I group); 105 women who had regularly used (>2 years) iodized salt prior to becoming pregnant (I-salt group); 160 women neither taking iodine supplements nor using iodized salt (no-I group). MEASUREMENTS: Maternal TSH, FT3 and FT4 were determined throughout gestation. RESULTS: Mean TSH concentrations were higher among the 150-I women than in the remaining two groups, and in a high proportion of them, TSH values were found to exceed the upper limit for gestational age. Conversely, the prevalence of low free-thyroxine levels in the 150-I women was similar to that observed in the I-salt women and markedly lower than that recorded for the no-I group. CONCLUSIONS: The regular use of iodine-containing supplements proved effective in reducing the risk of inappropriately low FT4 levels during pregnancy. The observed TSH increase in 150-I women may be because of a transient stunning effect on the thyroid gland, occurring as a result of the abrupt increase in daily iodine intake. Whilst the importance of gestational iodine supplementation is undisputed, we believe that in mild-moderately ID areas, women considering conception should be advised to take iodine supplementation for several months prior to pregnancy.

Nutritional iodine status and obesity.

Iodine is an essential component of the thyroid hormones, thyroxine and triiodothyronine. Its availability strictly depends on iodine content of foods, which may vary from very low to very high. Inadequate iodine intake (deficiency or excess) may affect thyroid function resulting in hypothyroidism or hyperthyroidism. Based on median urinary iodine concentrations, epidemiological criteria have been established for the categorization and monitoring of nutritional iodine status of a population (or subgroups of populations). Additional methods for iodine intake assessment include measurement of thyroid size (by thyroid palpation or ultrasonography) and of biochemical parameters, such as neonatal thyroid stimulating hormone, thyroglobulin and thyroid hormones.Recent studies carried out in overweight/obese children and adults provide evidence that body mass index (BMI) may significantly influence the above indicators, thus theoretically affecting the epidemiological evaluation of nutritional iodine status in populations.In this short review, we analyze current knowledge on the effects of overweight and obesity on indicators of adequacy and monitoring of iodine status, namely urinary iodine excretion and thyroid volume and echogenicity.Data on urinary iodine excretion in overweight/obese children are divergent, as both increased and reduced levels have been reported in overweight/obese children compared to normal-weight controls.Whether gastrointestinal surgery may affect iodine absorption and lead to iodine deficiency in patients undergoing bariatric surgery has been evaluated in a limited number of studies, which excluded iodine deficiency, thus suggesting that supplements usually recommended after bariatric surgery do not need to include iodine.Albeit limited, evidence on thyroid volume and obesity is consistent with a direct relationship between thyroid volume and BMI, irrespective of nutritional iodine status. Finally, a higher frequency of thyroid hypoechoic pattern has been described in overweight/obese children. This finding has been recently related to an increased adipocyte infiltration and thyroid parenchyma imbibition mediated by inflammatory cytokines and should be considered when the frequency of thyroid hypoechoic pattern is used as non-invasive marker to indirectly assess thyroid autoimmunity in monitoring Universal Salt Iodization programs. Further studies, specifically addressing the role of schoolchildren body mass index as a factor potentially influencing iodine intake indicators are needed.

Rates of lymphocytic thyroiditis and ultrasound features of citologically-interrogated thyroid nodules based on the area of residence in a Sicily province.

PURPOSE: To verify the prevalence of autoimmune thyroiditis (AIT) and the ultrasound characteristics (composition and volume) of thyroid nodules with respect to the area of residence in the province of Messina, some areas having environmental issues. METHODS: Fine-needle aspiration-interrogated nodules (n = 902) of 809 patients were evaluated upon stratification into 8 areas of residence. RESULTS: Overall, women were younger than men (55.3 ± 14.0 vs. 58.6 ± 12.6 years, P = 0.0083). Patients residing in three areas (one hosting two garbage dumps, one hosting a petrochemical complex and a thermoelectrical power plant, and one hosting several ceramic factories [CFA]) were younger than those residing in the city of Messina (MEA) (52.9 ± 13.4 vs. 57.7 ± 13.6 years, P < 0.0001). Also, patients residing in those three areas had a greater rate of AIT, diagnosed either ultrasonographically/serologically (22.2% of patients) or cytologically (26.3% of nodules), compared with MEA (11.7% of patients, P = 0.0007 or 20.2% of nodules, P = 0.0815). Rates of AIT ranged 12.5-28.6% in the remaining four areas. Overall, nodules in women were smaller than in men (3.6 ± 5.7 vs. 6.1 ± 9.4 ml, P = 0.0006). Compared with the other seven areas, patients living in CFA had the largest nodules (6.8 ± 6.8 ml, P = 0.0040-0.0291), with the nodule volume being inversely correlated to patient's age (r = -0.4955, P = 0.0431). CONCLUSION: Rates of AIT and associated ultrasound features of thyroid nodules vary in different areas of our province. Further studies correlating these rates and features with exposure to specific toxicants are warranted.

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.

Postpartum Thyroiditis in Women With Euthyroid and Hypothyroid Hashimoto's Thyroiditis Antedating Pregnancy.

CONTEXT: Postpartum thyroiditis (PPT) is defined as the occurrence of de novo autoimmune thyroid disease accompanied by thyroid dysfunction in the first year postpartum. However, hormonal changes resembling the typical pattern of PPT have been reported to occur even in women with pregestational Hashimoto's thyroiditis (HT) on levothyroxine (LT4). OBJECTIVE: To evaluate the risk of PPT in women with HT antedating pregnancy. DESIGN/SETTING: Retrospective chart review of pregnant women with HT antedating pregnancy seen in a university hospital (2008-2017), who were followed from preconception up to 1 year after delivery. PATIENTS: 167 women preconceptionally diagnosed with HT and classified as hypothyroid HT (hypo-HT; n = 98) or euthyroid HT (eu-HT; n = 69), according to their thyroid status at the time of diagnosis. OUTCOME MEASURES: PPT occurrence and associated clinical characteristics/risk factors. RESULTS: PPT occurred in 65/167 women, with a rate statistically greater in the eu-HT than in the hypo-HT group (68.1% vs 18.4%; odds ratio [OR] 9.49, 95% confidence interval [CI] 4.62-19.49). Most of the women experiencing PPT in both groups were euthyroid at the time of first-trimester evaluation (39/47 eu-HT [83%] and 16/18 hypo-HT [88.9%]). Multivariate regression analysis showed eu-HT group and first-trimester euthyroidism to be positively associated with PPT occurrence (ORs 10.71 and 3.89, respectively). CONCLUSION: PPT may occur in hypo-HT women on LT4 therapy, although significantly less frequently than in eu-HT women. The 4-fold higher risk of PPT in HT women maintaining euthyroidism at first -trimester of gestation suggests that the risk of PPT could be related to the amount of unaffected thyroid tissue.

Hyperthyroidism in the pregnant woman: Maternal and fetal aspects.

Hyperthyroidism during pregnancy is uncommon. Nonetheless, prompt identification and adequate management of hyperthyroidism in a pregnant woman is essential, because uncontrolled thyrotoxicosis significantly increases the risk of maternal and fetal complications. Also, fetal prognosis may be affected by the transplacental passage of maternal thyroid stimulating antibodies or thyrostatic agents, both of which may disrupt fetal thyroid function. Birth defects have been reported in association with the use of antithyroid drugs during early pregnancy. Although rarely, offspring of mothers with Graves' disease may develop fetal/neonatal hyperthyroidism, the management of which requires a close collaboration between endocrinologists, obstetricians, and neonatologists. Because of the above considerations, the management of pregnant and lactating women with hyperthyroidism requires special care, bearing in mind that both maternal thyroid excess per se and related treatments may adversely affect the newborn's health. In this review we discuss the diagnosis and management of hyperthyroidism in pregnancy, along with the impact of thyrotoxicosis and medications on fetal outcome.

Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency.

CONTEXT: Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny. These unfavorable effects are preventable by iodine supplementation. In Europe, however, less than 50% pregnant women receive iodine-containing supplements, thus representing dietary iodized salt the only carrier of iodine for most women in this life stage. OBJECTIVE/DESIGN: This longitudinal study is aimed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation. PARTICIPANTS/OUTCOME MEASURES: We prospectively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area. Sixty-two women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as long-term (LT) and short-term (ST) iodine supplemented, respectively. RESULTS: Long-term iodized salt consumption resulted in a very low prevalence of maternal thyroid failure (MTF) in LT women. Conversely, short-term iodine prophylaxis does not seem to protect against the risk of MTF, the prevalence of which was almost 6-fold higher in ST than LT women (36.8% vs. 6.4%; chi(2) 14.7, P < 0.0005; relative risk 5.7, 95% confidence interval 2.03-16.08, P < 0.001). The relative risk reduction amounted to 82.5%, this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women. CONCLUSIONS: Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation, probably because of a nearly restoring intrathyroidal iodine stores.

Differentiated thyroid carcinoma presentation may be more aggressive in children and adolescents than in young adults.

BACKGROUND: The available studies concerning the influence of age on the phenotypical expression of differentiated thyroid carcinoma (DTC) have hitherto compared DTC presentation either between pre-pubertal and pubertal children or between pediatric patients and aged adults; aim of this study was to ascertain for the first time whether presentation of DTC may significantly vary according to age, even within a peculiar study population covering only young patients aged less than 30 years. METHODS: The main clinical, biochemical and pathologic data at DTC diagnosis were retrospectively recorded in 2 selected cohorts including, respectively, 18 children and adolescents aged less than 18 years (Group A) or 45 young adults aged between 20 and 29.8 years (Group B). RESULTS: The statistical distribution of DTC cases in the different age ranges was found to progressively increase with increasing age; furthermore, the patients of Group A exhibited at diagnosis a more severe clinical involvement and a higher rate of extra-regional metastases; finally, also the association with both autoimmune thyroid diseases (AITDs) and a biochemical hypothyroid pattern was more common in Group A patients. CONCLUSIONS: In a study population younger than 30 years: a) the risk of developing DTC increases with age, achieving its zenith during the 3rd decade of life; b) clinical presentation is more severe in children and adolescents younger than 18 years than in the patients aged between 20 and 30; c) in the cohort of children and adolescents DTC is more often associated with AITDs, which might play some role in conditioning the more aggressive phenotypical presentation of DTC in this patient group.

Thyroid cancer in lingual thyroid and thyroglossal duct cyst.

Ectopy is the most common embryogenetic defect of the thyroid gland, representing between 48 and 61% of all thyroid dysgeneses. Persistence of thyroid tissue in the context of a thyroglossal duct remnant and lingual thyroid tissue are the most common defects. Although most cases of ectopic thyroid are asymptomatic, any disease affecting the thyroid may potentially involve the ectopic tissue, including malignancies. The prevalence of differentiated thyroid carcinoma in lingual thyroid and thyroglossal duct cyst is around 1% of patients affected with the above thyroid ectopies. We here review the current literature concerning primary thyroid carcinomas originating from thyroid tissue on thyroglossal duct cysts and lingual thyroid.

Female Reproductive Factors and Differentiated Thyroid Cancer.

Differentiated thyroid cancer (DTC) is markedly more common in women than men, the highest female-to-male ratio being recorded during the reproductive period. This evidence has led to the suggestion that female hormonal and reproductive factors may account for the observed DTC gender disparity. This review focuses on current evidence on the risk of DTC in conjunction with major female reproductive factors, including the impact of pregnancy on DTC occurrence and progression/recurrence. Overall, studies exploring the link between the risk of DTC and menstrual and menopausal factors, oral contraceptives and/or hormone replacement therapy, showed these associations, if any, to be generally weak. Nonetheless, there is some evidence that higher levels of exposure to estrogens during reproductive years may confer an increased risk of DTC. As far as pregnancy is concerned, it is unclear whether a potential association between parity and risk of DTC actually exists, and whether it is enhanced in the short-term following delivery. A possible role for pregnancy-related factors in DTC progression has been recently suggested by some reports, the results of which are consistent with a worse outcome in the short-term of women diagnosed with DTC during gestation compared to non-pregnant control patients. Also, some progression of disease has been described in women with structural evidence of disease prior to pregnancy. However, there seems to be no impact from pregnancy in DTC-related death or overall survival. Several in vitro and animal studies have evaluated the influence of estrogens (E) and estrogen receptors (ERs) on thyroid cell proliferation. Presently available data are indicative of a role of E and ERs in thyroid cancer growth, although considerable discrepancies in respect to ER expression patterns in thyroid cancer tissues actually exist. Further studies providing more direct evidence on the possible role of E and of placental hormones and growth factors on thyroid growth may expand our knowledge on the mechanisms beyond the gender disparity of proliferative thyroid diseases.

antiphospholipid antibodies syndrome associated with hyperhomocysteinemia related to MTHFR Gene C677T and A1298C heterozygous mutations in a young man with idiopathic hypoparathyroidism (DiGeorge syndrome).

CONTEXT: Antiphospholipid syndrome (APS, or Hughes' syndrome) is a systemic autoimmune disorder characterized by antiphospholipid antibody positivity, which may lead to arterial and/or venous thrombosis. Hyperhomocysteinemia (HHcy), variously associated with 5,10-methylene tetrahydrofolate reductase (MTHFR) gene point mutations, is also implicated in thromboembolic events. The association of APS and HHcy has already been described but has never been reported in patients with DiGeorge syndrome (DGS), the most common contiguous-gene deletion syndrome (22q11.2) in humans, whose phenotype conversely includes bleeding disorders. DATA ACQUISITION: In this report, we present the case of a 19-yr-old patient with a past medical history of learning disability and obesity affected with idiopathic hypoparathyroidism, metabolic syndrome, and diffuse vasculitis disorders. He was referred to our endocrinology clinic for the management of severe hypocalcemia. At the time of presentation he had been taking antiepileptic drugs for 2 wk and displayed facial dysmorphism (short neck, micrognathia, a small mouth, hypoplastic nasal alae, eye hypertelorism, and low-set simple ears). DGS was suspected and confirmed by both fluorescence in situ hybridization analysis and single nucleotide polymorphism-array analysis, which revealed contiguous gene microdeletion of the chromosome 22q11.2 in the minimal DiGeorge critical region, specifically at the gene locus D22S75 (N25). CONCLUSIONS: APS, revealed by anti-beta-2-glycoprotein and anti-prothrombin antibodies positivity, and moderate HHcy related to heterozygous C677T and A1298C point mutations of the MTHFR gene were identified as a possible cause of thrombotic disorder responsible for the widespread presence of cutaneous and cerebral lesions.

The changing phenotype of iodine deficiency disorders: a review of thirty-five years of research in north-eastern Sicily.

Iodine deficiency disorders (IDD) still represent a major public health problem, with almost 30% of the world population being exposed to the consequences of nutritional iodine deficiency (ID). In Italy, despite a sustained policy of iodine prophylaxis, more than 10% of people is still affected with goiter, and a presumably higher rate of subjects may suffer from minor cognitive deficits due to inadequate iodine supply during antenatal life. This review of systematic observational studies carried out over thirty-five years (1980-2015) in a sentinel ID area in North-eastern Sicily highlights the changing phenotypes of IDD in this region. Over the years profound improvements in nutritional iodine status in North-eastern Sicily has occurred, due to both silent and active iodine prophylaxis. Endemic cretinism, resulting from severe iodine deficiency, has been progressively replaced by less serious deficits of intellectual and cognitive abilities, which nevertheless deserve proper attention.

Immunohistochemical Expression of Estrogen Receptor-α and Progesterone Receptor in Patients with Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) prevalence is nearly 3 times higher in females than in males. This gender difference suggests that growth and progression of PTC might be influenced by female sex hormones. OBJECTIVES: To analyze the expression of both estrogen receptor (ER)-α and progesterone receptor (PR) by immunohistochemistry in 203 PTC patients. METHODS: ER-α and PR expression was evaluated in paraffin-embedded tumor tissue samples of 45 males and 158 females followed up for 7.2 ± 3.7 years. RESULTS: ER-α was expressed in 52 (25.6%) patients (41 females and 11 males) and PR in 94 (46.3%) patients (75 females and 19 males). ER-α and PR were coexpressed in 31 (15.3%) patients (27 females and 4 males). ER-α expression correlated significantly with tumor size in the whole sample (ER-α positive 22.8 ± 11.8 mm vs. ER-α negative 15.1 ± 12.4 mm; p = 0.02) and in the subgroup of women (ER-α positive 18.8 ± 12.8 mm vs. ER-α negative 14.9 ± 12.3 mm; p = 0.048). In addition, ER-α expression significantly correlated with remission of the disease. In fact, of the 192 patients followed up, 50/153 (32.7%) disease-free patients were ER-α positive, in contrast to only 3/39 (7.7%) with evidence of disease persistence/recurrence (χ2 = 8.5, p = 0.0036). PR expression was not associated with any of the parameters analyzed. CONCLUSIONS: The present study confirmed recent data indicating that ER-α and PR expression is a common finding in thyroid tumor tissue. However, in contrast to previous reports, we observed an association between ER-α expression and a more favorable outcome in PTC patients.