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.

Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.

Role of ER Stress Mediated Unfolded Protein Responses and ER Stress Inhibitors in the Pathogenesis of Inflammatory Bowel Disease.

Previous investigations have increased the knowledge about the pathological processes of inflammatory bowel diseases. Besides the complex organization of immune reactions, the mucosal epithelial lining has been recognized as a crucial regulator in the commencement and persistence of intestinal inflammation. As the intestinal epithelium is exposed to various environmental factors, the intestinal epithelial cells are confronted with diverse cellular stress conditions. In eukaryotic cells, an imbalance in the endoplasmic reticulum (ER) might cause aggregation of unfolded or misfolded proteins in the lumen of ER, a condition known as endoplasmic reticulum stress. This cellular mechanism stimulates the unfolded protein response (UPR), which elevates the potential of the endoplasmic reticulum protein folding, improves protein production and its maturation, and also stimulates ER-associated protein degradation. Current analyses reported that in the epithelium, the ER stress might cause the pathogenesis of inflammatory bowel disease that affects the synthesis of protein, inducing the apoptosis of the epithelial cell and stimulating the proinflammatory reactions in the gut. There have been significant efforts to develop small molecules or molecular chaperones that will be potent in ameliorating ER stress. The restoration of UPR balance in the endoplasmic reticulum via pharmacological intervention might be a novel therapeutic approach for the treatment of inflammatory bowel diseases (IBDs). This review provides novel insights into the role of chemical chaperone UPR modulators to modify ER stress levels. We further discuss the future directions/challenges in the development of therapeutic strategies for IBDs by targeting the ER stress. Figure depicting the role of endoplasmic reticulum stress-mediated inflammatory bowel disease and the therapeutic role of endoplasmic reticulum stress inhibitors in alleviating the diseased condition.

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.

Immunolocalization of leptin and leptin receptor in colorectal mucosa of ulcerative colitis, Crohn's disease and control subjects with no inflammatory bowel disease.

The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn's disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas.

Faecal microbiota transplantation in Clostridioides difficile infection: real-life experience from an academic Italian hospital.

BACKGROUND: Faecal microbiota transplantation (FMT) is a reasonable therapeutic option for the treatment of Clostridioides difficile infection (CDI) recurrent and refractory (RCDI) to therapy, but little evidence on the long-term impact of this therapy is currently available in the literature. The aim of this study was to evaluate the efficacy and safety of FMT in recurrent and refractory CDI and the modifications of the recipient's gut microbiota in the medium-long term. METHODS: This prospective study collects the clinical and laboratory data of RCDI patients treated with FMT by colonoscopy from February 2016 to October 2019. Stool samples for metagenomic analysis were collected pre-FMT at 1 week and at 6 and 12-24 months post-FMT. RESULTS: In the study period, 20 FMT procedures were performed on 19 patients. Overall, FMT was effective in 85% of treated patients. No serious adverse event was recorded. In the medium- to long-term follow up, a newly diagnosed case of collagenous colitis was observed. Post-FMT, significant changes in microbiota were observed, characterised by the transition from a low- to a greater-diversity profile. Therefore, FMT restores eubiosis and maintains it over time. CONCLUSION: FMT is a safe and effective treatment option in RCDI patients. This procedure induces profound microbiota changes that explain its high clinical efficacy.

Microbiota changes induced by microencapsulated sodium butyrate in patients with inflammatory bowel disease.

BACKGROUND: Butyrate has shown anti-inflammatory and regenerative properties, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. We investigated the effect of a colonic-delivery formulation of butyrate on the fecal microbiota of patients with inflammatory bowel diseases (IBDs). METHODS: In this double-blind, placebo-controlled, pilot study, 49 IBD patients (n = 19 Crohn's disease, CD and n = 30 ulcerative colitis, UC) were randomized to oral administration of microencapsulated-sodium-butyrate (BLM) or placebo for 2 months, in addition to conventional therapy. Eighteen healthy volunteers (HVs) were recruited to provide a healthy microbiota model of the local people. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity and quality of life (QoL) were evaluated before and after treatment. KEY RESULTS: At baseline, HVs showed a different microbiota composition compared with IBD patients. Sodium-butyrate altered the gut microbiota of IBD patients by increasing bacteria able to produce SCFA in UC patients (Lachnospiraceae spp.) and the butyrogenic colonic bacteria in CD patients (Butyricicoccus). In UC patients, QoL was positively affected by treatment. CONCLUSIONS AND INFERENCES: Sodium-butyrate supplementation increases the growth of bacteria able to produce SCFA with potentially anti-inflammatory action. The clinical impact of this finding requires further investigation.

Diffusion-weighted magnetic resonance for assessing fibrosis in Crohn's disease.

BACKGROUND: Intestinal fibrosis is a key feature of Crohn's Disease lesions, and mucosal biopsies do not exactly represent transmural damage. Magnetic resonance enterography (MRE) allows for a panoramic study of the bowel loops. Diffusion-weighted imaging (DWI) through the restriction of the apparent diffusion coefficient (ADC) allows for an accurate evaluation of disease activity in Crohn's Disease patients avoiding contrast agents. The aim of this study was to investigate whether DWI sequences were able to identify intestinal fibrosis in candidates for surgery, using histopathology as the gold standard. MATERIALS AND METHODS: Thirty Crohn's Disease patients undergoing surgery for stricturing ileo-colonic disease were consecutively enrolled from October 2010 to November 2015. All patients underwent MRE with DWI before surgery. Radiological parameters were calculated in the stenotic segment and in the ileum proximal to the stenosis. The histopathological examination was performed using a histological score for fibrosis and inflammation. RESULTS: ADC value correlated with the fibrosis score (r = -0.648; p < 0.0001), inflammation score (r = -0.763; p < 0.0001) and percentage of gain (r = -0.687; p < 0.0001). A correlation emerged between wall thickness and fibrosis score (r = 0.671; p < 0.0001). The threshold of wall thickness for fibrosis was > 6.3 mm (AUC 0.89, specificity 100% and sensitivity 69.23%). The cut-off of ADC value for fibrosis was < 1.1 × 10-3 mm2 s-1 with a sensitivity of 72% and specificity of 94% (AUC = 0.83). CONCLUSIONS: The DWI sequence with ADC value could be useful to identify fibrosis in the intestinal wall of Crohn's Disease patients.

A Phase 2a, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial of IBD98-M Delayed-Release Capsules to Induce Remission in Patients with Active and Mild to Moderate Ulcerative Colitis.

IBD98-M is a delayed-release formulation of mesalamine (mesalazine) and SH with a potential therapeutic role in ulcerative colitis (UC). A total of 51 patients with a modified Ulcerative Colitis Disease Activity Index (UCDAI) score of ≥4 and ≤10, and a modified UCDAI endoscopy subscore ≥1 were randomized for 6 weeks of double-blind treatment with IBD98 0.8 g/day or IBD 1.2 g/day or placebo. The efficacy and safety of IBD98-M in mild to moderate active UC were primarily evaluated. At week 6, 1 (5.9%), 2 (12.5%), and 2 (11.1%) patients receiving IBD98-M 0.8 g, IBD98-M 1.2 g, and placebo, respectively, (p > 0.999) achieved clinical remission. Higher clinical response was seen in IBD98-M 1.2 g (31.3%) versus placebo (16.7%) and endoscopic improvement in IBD98-M 0.8 g (29.4%) versus placebo (22.2%) was seen. Fecal calprotectin levels were reduced in IBD98-M groups versus placebo (p > 0.05). IBD98-M patients achieved significant improvement in physical health summary score component of the SF-36 (p = 0.01 and p = 0.03 respectively) compared to placebo. IBD98-M did not meet the primary end point but had higher clinical response (1.2 g/day) and endoscopic improvement (0.8 g/day) compared to placebo. The safety result shown that IBD98-M treatment was safe and well tolerated in this patient population. No new safety signals or unexpected safety findings were observed during the study. Further trials with different stratification and longer follow-up may be needed to evaluate the efficacy.

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.

Inflammatory Bowel Disease Therapies Adversely Affect Fertility in Men- A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Sexual functions are sometimes adversely affected by the therapeutic drugs delivered for treating IBD. Much attention has been focused on pregnancy/sexual issues in women. Relatively less attention has been poured in to address this issue in men. This systematic review assesses the drugs having potential detrimental effects on fertility in men. METHODS: Three databases were searched by two researchers independently for potentially relevant publications between 1964 to 2015 and 249 papers were retrieved. Studies that dealt with sexual problems after IBD drugs administration were included in the purview of this review. RESULTS: Fourteen studies with 327 human patients and 110 animals were analysed. Sulphasalazine treated patients had lower spermatozoa count, lower sperm motility and higher risk of oligospermia compared to mesalazine treated ones. Biologics seem to be safe to use while attempting to conceive however, proper clinical studies reporting male fertility problems in IBD patients are lacking. Azathioprine caused oligospermia but a meta-analytical approach was not possible due to heterogeneity in studies. Some animal studies showed methotrexate affects abnormal testis structure and spermatogenesis. CONCLUSION: This study summarises the current literature and safety issues affecting fertility parameters in men and animals treated with IBD therapeutic drugs, which can further assist clinicians in better management of adult male IBD patients.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

BACKGROUND AND AIMS: Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. METHODS: This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. RESULTS: In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. CONCLUSIONS: In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

Quality of life after laparoscopic sigmoid resection for uncomplicated diverticular disease.

PURPOSE: The study aimed to evaluate the QoL in patients who underwent elective surgery for uncomplicated diverticulitis using a recently developed diverticulitis quality of life questionnaire (DV-QoL). METHODS: All consecutive patients who underwent surgery for uncomplicated diverticulitis or who were hospitalized and treated conservatively for acute uncomplicated diverticulitis episodes in three referral centers, in a 5-year period, were included in the study. The 36-Item Short Form Survey and the DV-QoL were administered to the patients to assess their QoL before and after treatment of diverticular disease. RESULTS: Ninety-seven patients who underwent surgery, 44 patients who were treated conservatively, and 44 healthy volunteers were included in the study. DV-QoL scores correlated with SF-36 scores (p < 0.0001). The surgically treated patients reported a worse quality of life before treatment with respect to the patients treated conservatively (mean 21.12 surgical vs 15.41 conservative, p = 0.0048). The surgically treated patients presented better post-treatment global scores with respect to the conservatively treated patients (mean: 6.90 surgical vs 10.61 conservative, p = 0.0186). Covariance analysis confirmed that the differences between the pre- and post-treatment DV-QoL scores were significantly higher in the surgical (p = 0.0002) with respect to the non-surgical patients. As far as single items were concerned, differences between the two groups were found in the pre- and post-treatment "concerns" and "behavioral changes" DV-QoL items. CONCLUSIONS: Sigmoidectomy reduces concerns about diverticulitis and behavioral changes due to the disease. Quality of life should be considered when referring patients with uncomplicated diverticulitis to surgery. Prospective studies are required to confirm this result.

Glucose transporter expression in the human colon.

AIM: To investigate by immunostaining glucose transporter expression in human colorectal mucosa in controls and patients with inflammatory bowel disease (IBD). METHODS: Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or recto-sigmoidoscopy. Patients diagnosed with ulcerative colitis (n = 18) or Crohn's disease (n = 10) and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or had a history of lower gastrointestinal symptoms were designated as the control group (CTRL, n = 16). Inflammatory status of the mucosa at the sampling site was evaluated histologically and/or endoscopically. A total of 147 biopsies of colorectal mucosa were collected and processed for immunohistochemistry analysis. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. To compare immunoreactivity of GLUT5 and LYVE-1, which is a marker for lymphatic vessel endothelium, double-labeled confocal microscopy was used. RESULTS: Immunohistochemical analysis revealed that GLUT2, SGLT1, and GLUT5 were expressed only in short epithelial portions of the large intestinal mucosa. No important differences were observed in glucose transporter expression between the samples obtained from the different portions of the colorectal tract and between the different patient groups. Unexpectedly, GLUT5 expression was also identified in vessels, mainly concentrated in specific areas where the vessels were clustered. Immunostaining with LYVE-1 and GLUT5 antibodies revealed that GLUT5-immunoreactive (-IR) clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. GLUT5 and LYVE-1 did not appear to be colocalized but rather showed a close topographical relationship on the endothelium. Based on their LYVE-1 expression, GLUT5-IR vessels were identified as lymphatic. Both inflamed and non-inflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients showed GLUT5-IR clusters of lymphatic vessels. CONCLUSION: Glucose transporter immunoreactivity is present in colorectal mucosa in controls and IBD patients. GLUT5 expression is also associated with lymphatic vessels. This novel finding aids in the characterization of lymphatic vasculature in IBD patients.

Prediction of clinical outcomes in Crohn's disease by using confocal laser endomicroscopy: results from a prospective multicenter study.

BACKGROUND AND AIMS: Assessment of prognostic factors in patients with Crohn's disease (CD) is of pivotal importance for early intervention and "treat-to-target" strategies. Confocal laser endomicroscopy (CLE) enables on-demand in vivo characterization of mucosal inflammatory and architectural changes during endoscopy. We prospectively assessed the value of CLE for prediction of clinical outcome parameters in CD. METHODS: Consecutive patients with CD undergoing colonoscopy were included in a multicenter study. Confocal imaging focused on 2 highly reproducible histologic hallmarks of active colonic inflammation: focal cryptitis and crypt architectural abnormality. We evaluated whether CLE, CD endoscopic index of severity (CDEIS), serum C-reactive protein (CRP), and CD activity index (CDAI) were associated with the risk of medical treatment escalation, transmural adverse events, and CD-related hospitalization or surgery during a 4-year follow-up. RESULTS: Among 49 patients (53% men, median age, 39 years), baseline CRP was ≥5 mg/L in 47%, CDEIS ≥3 in 75%, and CDAI >150 in 51%. Focal cryptitis and crypt architectural abnormality were observed in 63% (CLE+ group). CLE+ patients showed an increased incidence of medical treatment escalation (P < .001; relative risk [RR] = 3.27) and transmural lesions (P = .025; RR = 1.70), whereas patients with CRP ≥5 mg/L had increased CD-related hospitalization and surgery (P = .020, RR = 2.71) at 1-year follow-up. No further association with prognostic clinical outcomes was found over the 1-year follow-up as well as for CDEIS and CDAI at any time. CONCLUSIONS: CLE reveals CD-related features of mucosal inflammation and allows for early prediction of relevant clinical outcomes. Further studies should now address whether this promising prognostic tool could refine the timing of treatment strategies in patients with CD.

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.

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.