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Background: Observational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. Objectives: To evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. Methods: We studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. Results: Median urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31–1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. Discussion: Gestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.

Το πρώτο τρίμηνο της κύησης θεωρείται ένα κρίσιμο χρονικό διάστημα της εμβρυικής ανάπτυξης, ιδιαίτερα επιρρεπές σε ενδογενείς ή εξωγενείς επιβλαβείς παράγοντες. Πέραν της παχυσαρκίας, κατά την κύηση δεν έχει μελετηθεί επαρκώς μέχρι σήμερα η επίδραση άλλων παραμέτρων του μεταβολικού συνδρόμου και ιδιαιτέρως, των παραγόντων εκείνων του ενδομητρίου περιβάλλοντος οι οποίοι επηρρεάζουν την ανάπτυξη του λιπώδους ιστού και του νευρικού συστήματος στο αναπτυσσόμενο έμβρυο. Παραδείγματος χάριν, αν και είναι γνωστό ότι τα επίπεδα βιταμίνης D της μητέρας αποτελούν σημαντικό παράγοντα για την ομαλή ανάπτυξη των οστών και του μυικού συστήματος του εμβρύου, λίγα είναι γνωστά για τον πιθανό ρόλο της βιταμίνης D στην εναπόθεση του λίπους και την νευροανάπτυξη των απογόνων. Στόχος της παρούσας διατριβής ήταν να διερευνήσει: 1)Τη σχέση παραγόντων του μεταβολικού συνδρόμου στις εγκύους, στο 1ο τρίμηνο κύησης με α) την σωματική ανάπτυξη και την εμφάνιση παραγόντων καρδιαγγειακού κινδύνου και β) την νευροανάπτυξη παιδιών ηλικίας 4 ετών 2) Τη σχέση των επιπέδων 25(ΟΗ)D στις εγκύους, στο 1ο τρίμηνο κύησης με α) την σωματική ανάπτυξη και την εμφάνιση παραγόντων καρδιαγγειακού κινδύνου και β) την νευροανάπτυξη παιδιών ηλικίας 4 ετών. Μεθοδολογία: Ο πληθυσμός της παρούσας διατριβής προέρχεται από την προοπτική μελέτη Μητέρας-Παιδιού «Ρέα», στην οποία εντάχθηκαν έγκυες κατά τη διάρκεια ενός έτους (Φβρουάριος 2007-Φεβρουάριος 2008). Οι μητέρες εκτιμήθηκαν κλινικά στο 1ο τρίμηνο της κύησης, κατά τη διάρκεια του 1ου υπερηχογραφήματος του εμβρύου, με προσδιορισμό του ύψους και του βάρους από ειδικά εκπαιδευμένους εξεταστές. Ταυτόχρονα συλλέχτηκαν πληροφορίες για το βάρος των εγκύων πριν την εγκυμοσύνη και υπολογίστηκε ο δείκτης μάζας σώματος προ της κύησης. Στην ίδια συνέντευξη εκτιμήθηκε η συστολική και διαστολική πίεση και συλλέχθηκαν βιολογικά δείγματα για τον προσδιορισμό των συγκεντρώσεων σακχάρου, λιπιδίων και 25(ΟΗ)-βιτ D των εγκύων. Στα 4 έτη παρακολούθησης, ειδικά εκπαιδευμένοι ερευνητές πεδίου, ακολουθώντας συγκεκριμένα πρωτοκολλα, μέτρησαν το βάρος, το ύψος, την περίμετρο μέσης, τις δερματικές πτυχές και την αρτηριακή πίεση των παιδιών, ενώ ταυτόχρονα συλλέχθηκαν βιολογικά δείγματα για τον προσδιορισμό των λιπιδίων στην προσχολική ηλικία. Όσον αφορά την ψυχοκινητική ανάπτυξη των παιδιών στα 4 έτη ζωής, ειδικά εκπαιδευμένοι ψυχολόγοι την αξιολόγησαν χρησιμοποιώντας τις Κλίμακες Εκτίμησης Παιδικών Δεξιοτήτων (McCarthy Scales of Children's Abilities). Επίσης η αξιολόγηση διαταραχών στη συμπεριφορά των παιδιών έγινε με τη συμπλήρωση από τις μητέρες ειδικών ερωτηματολογίων που αφορούσαν τις δυνατότητες και τις δυσκολίες συμπεριφοράς των παιδιών τους (SDQ questionnaire), καθώς και την εκδήλωση συμπτωμάτων ελείμματος προσοχής-υπερκινητικότητας (ADHD Test) στην προσχολική ηλικία. Τα δεδομένα που συλλέχθηκαν αναλύθηκαν με πολυπαραγοντικά μοντέλα γραμμικής και λογιστικής παλινδρόμησης. Αποτελέσματα: Ο αυξημένος δείκτης μάζας σώματος της μητέρας πριν την εγκυμοσύνη βρέθηκε να σχετίζεται στη μελέτη μας με αυξημένο κίνδυνο υπέρβαρου/παχύσαρκου παιδιού στα 4 έτη ζωής, καθώς και αυξημένο κίνδυνο κεντρικής παχυσαρκίας και αυξημένης ποσότητας λιπώδους μάζας στην προσχολική ηλικία. Επίσης αύξηση της συγκέντρωσης της ολικής χοληστερόλης της μητέρας στο 1ο τρίμηνο κύησης κατά 40mg/dl βρέθηκε να συσχετίζεται με αυξημένο κίνδυνο υπέρβαρου/παχύσαρκου παιδιόυ και αυξημένο πάχος δερματικών πτυχών στα 4 έτη ζωής. Από το σύνολο των παραγόντων του μεταβολικού συνδρόμου στο 1ο τρίμηνο κύησης που μελετήσαμε, μόνο η παχυσαρκία της μητέρας πριν την κύηση βρέθηκε να συσχετίζεται με σημαντικά χαμηλότερη επίδοση στην αντιληπτική, στην αριθμητική και στη γενική γνωστική ικανότητα καθώς και στις επιτελικές λειτουργίες του μετωπιαίου λοβού των απογόνων στα 4 έτη ζωής. Επίσης η παχυσαρκία της μητέρας πριν την κύηση βρέθηκε να συσχετίζεται με αύξηση της εμφάνισης διαταραχών συμπεριφοράς και εκδήλωσης συμπτωμάτων ελλειματικής προσοχής-υπερκινητικότητας των παιδιών στα 4 έτη ζωής. Κατά τη διερεύνηση της επίδρασης των συγκεντρώσεων της 25(OH) βιτ D στο 1ο τρίμηνο κύησης στην υγεία των παιδιών προσχολικής ηλικίας, βρέθηκε ότι οι απόγονοι γυναικών με επίπεδα 25(ΟΗ) βιτ D στο χαμηλότερο τριτημόριο είχαν σημαντικά αυξημένο BMI SD score, αυξημένη κεντρικού τύπου παχυσαρκία και υψηλότερο ποσοστό λίπους στα 4 έτη ζωής, συγκρινόμενοι με τους απογόνους γυναικών με υψηλότερα επίπεδα 25(ΟΗ) βιτ D, στο πρώτο μισό της κύησης. Από την άλλη πλευρά, οι απόγονοι μητέρων με επίπεδα 25(ΟΗ) βιτ D στο υψηλότερο τριτημόριο είχαν σηματικά λιγότερα συμπτωμάτα υπερκινητικότητας-παρορμητικότητας και γενικά λιγότερα συμπτωμάτα ελλειματικής προσοχής (ADHD) καθώς και λιγότερα προβλήματα συμπεριφοράς στα 4 έτη ζωής, συγκρινόμενοι με απογόνους μητέρων με χαμηλότερα επίπεδα 25(ΟΗ) βιτ D στην κύηση. Οι ανωτέρω συσχετίσεις παρέμεναν σημαντικές ύστερα από τον έλεγχο διαφόρων συγχυτικών παραγόντων συμπεριλαμβανομέενου του δείκτη μάζας σώματος της μητέρας πριν την κύηση και ήταν πιο ισχυρές στα κορίτσια από ότι στα αγόρια. Συμπεράσματα: Συνοψίζοντας όλα τα παραπάνω, η παρούσα μελέτη έδειξε ότι τα μεταβολικά νοσήματα της μητέρας και τα επίπεδα βιταμίνης D στο 1ο τρίμηνο της κύησης, παίζουν σημαντικό ρολο στην εκδήλωση παχυσαρκίας και διαταραχών στην νευροανάπτυξης παιδιών προσχολικής ηλικίας, ανεξάρτητα από κοινωνικοδημογραφικούς και γενετικούς παράγοντες.

Maintaining thyroid homeostasis during pregnancy is vital for fetal development. The few studies that have investigated associations between metal exposure and gestational thyroid function have yielded mixed findings. To evaluate the association of exposure to a mixture of toxic metals with thyroid parameters in 824 pregnant women from the Rhea birth cohort in Crete, Greece. Concentrations of three toxic metals [cadmium (Cd), antimony (Sb), lead (Pb)] and iodine were measured in urine using inductively coupled plasma mass spectrometry and thyroid hormones [Thyroid Stimulating Hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3)] were measured in serum in early pregnancy. Associations of individual metals with thyroid parameters were assessed using adjusted regression models, while associations of the metal mixture with thyroid parameters were assessed using Bayesian Kernel Machine Regression (BKMR).Women with high (3rd tertile) concentrations of urinary Cd, Sb and Pb, respectively, had 13.3 % (95%CI: 2.0 %, 23.2 %), 12.5 % (95%CI: 1.8 %, 22.0 %) and 16.0 % (95%CI: 5.7 %, 25.2 %) lower TSH compared to women with low concentrations (2nd and 1st tertile). In addition, women with high urinary Cd had 2.2 % (95%CI: 0.0 %, 4.4 %) higher fT4 and 4.0 % (95%CI: −0.1 %, 8.1 %) higher fT3 levels, and women with high urinary Pb had 4 % (95%CI: 0.2 %, 8.0 %) higher fT3 levels compared to women with low exposure. The negative association of Cd with TSH persisted only when iodine sufficiency was unfavorable. BKMR attested that simultaneous exposure to toxic metals was associated with decreased TSH and increased fT3 and revealed a potential synergistic interaction of Cd and Pb in association with TSH. The present results suggest that exposure to toxic metals even at low levels can alter gestational thyroid homeostasis.

The 3PAs association describes the coexistence of pituitary adenoma, pheochromocytoma (PHEO), and paraganglioma (PGL). There are 90 3PAs cases reported in the literature (with and without genetic mutations/variants) since 1952. Most cases carry SDHx defects, whereas MEN1 and MAX are the second and third most common genes involved. Overall, pituitary adenomas in 3PAs with genetic defects are significantly more common among familial cases, more frequently macroadenomas secreting PRL or growth hormone; they often lead to multiple phenotypes within the same family and require multiple treatment modalities. A distinctive pathologic feature of SDHx-mutated pituitary adenomas is an extensive vacuolization of the cytoplasm. Utilizing the Sdhb+/− mouse model, we found increased HIF-1 expression in adenohypophyseal cells and mitochondrial and nuclear abnormalities. Patients presenting with 3PAs should be initially screened for SDHx mutations, particularly if there is a history of PHEOs/PGLs in other family members. If family history is negative, screening for SDHx, MEN1, and MAX mutations may be considered.

Interleukin 6 (IL-6), a proinflammatory cytokine, is elevated in patients with type 2 diabetes (T2D), and is considered an independent predictor of T2D. IL-6 single-nucleotide polymorphisms (SNPs) have been associated with higher levels of IL-6. This study investigated the role of an IL-6 gene polymorphism and its possible association to T2D in the genetically homogeneous Greek population of the island of Crete.A total of 144 patients with T2D and 180 controls, all Cretans, selected from the Diabetes Clinic and the Department of Internal Medicine at the University Hospital of Heraklion, Crete, Greece, were genotyped for the IL-6 -174GC (rs1800795) SNP by the restriction fragment length polymorphism method.The G/C genotype and the minor allele C of the IL-6 rs1800795 SNP were more common in individuals with T2D than controls (p = 0.004, odds ratio [OR] = 1.98, 95% confidence interval [CI]: 1.24-3.18 and p = 0.011, OR = 1.59, 95% CI: 1.11-2.26, respectively).An association of the rs1800795 SNP of the IL-6 gene with T2D has been detected for the first time in Cretans. The present results, in combination with those presented previously from different ethnic/racial populations, highlight the necessity of comparative studies among different ethnic/racial populations to detect genetic characteristics and associations with T2D.

Background Hypocalcaemia is a common and serious complication after thyroidectomy. The purpose of this study is to assess the effectiveness of first postoperative day parathyroid hormone (PTH) measurement in order to predict the presence and severity of postthyroidectomy hypocalcaemia. Methods One hundred consecutive cases undergoing total thyroidectomy in a tertiary referral center were prospectively assessed. Preoperative measurements of PTH were compared with postoperative levels in the first morning after surgery. All cases of hypocalcaemia were recorded and evaluated with regard to preoperative and postoperative levels of PTH. Results A decrease of 56% of PTH levels on the first postoperative day could accurately predict postoperative hypocalcaemia with a sensitivity and specificity of 80%. Conclusion Serum PTH levels on the first postoperative day may be used as a reliable predictive marker for calcium supplementation need and even prolonged hospitalization in cases undergoing total thyroidectomy.

Purpose: The study assessed whether diet and adherence to cancer prevention guidelines during pregnancy were associated with micronucleus (MN) frequency in mothers and newborns. MN is biomarkers of early genetic effects that have been associated with cancer risk in adults. Methods: A total of 188 mothers and 200 newborns from the Rhea cohort (Greece) were included in the study. At early-mid pregnancy, we conducted personal interviews and a validated food frequency questionnaire was completed. With this information, we constructed a score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention guidelines on diet, physical activity and body fatness. At delivery, maternal and/or cord blood was collected to measure DNA and hemoglobin adducts of dietary origin and frequencies of MN in binucleated and mononucleated T lymphocytes (MNBN and MNMONO). Results: In mothers, higher levels of red meat consumption were associated with increased MNBN frequency [2nd tertile IRR = 1.34 (1.00, 1.80), 3rd tertile IRR = 1.33 (0.96, 1.85)] and MNMONO frequency [2nd tertile IRR = 1.53 (0.84, 2.77), 3rd tertile IRR = 2.69 (1.44, 5.05)]. The opposite trend was observed for MNBN in newborns [2nd tertile IRR = 0.64 (0.44, 0.94), 3rd tertile IRR = 0.68 (0.46, 1.01)], and no association was observed with MNMONO. Increased MN frequency in pregnant women with high red meat consumption is consistent with previous knowledge. Conclusions: Our results also suggest exposure to genotoxics during pregnancy might affect differently mothers and newborns. The predictive value of MN as biomarker for childhood cancer, rather than adulthood, remains unclear. With few exceptions, the association between maternal carcinogenic exposures during pregnancy and childhood cancer or early biologic effect biomarkers remains poorly understood. The Rhea cohort was funded by the following European projects NewGeneris (FP-6-FOOD-CT-2005-016320), ESCAPE (FP7-2007-211250), HiWATE (FP-6-FOOD-CT-2006-036224), Envirogenomarkers (FP7-2008-ENV-1.2.1.4), CHICOS (FP7-2009-GA 241604), and ENRIECO (FP7-2008-GA 226285). COG holds a Sara Borrell postdoctoral fellowship awarded from the Carlos III National Institute of Health (CD13/00072). MP held a Juan de la Cierva postdoctoral fellowship awarded from the Spanish Ministry of Ministry of Economy and Competitiveness (JCI-2011-09479). DFM received support from the Italian Ministry of Health, 5x1000 Grant-2011.

BACKGROUND Vitamin D may modulate adipogenesis. However, limited studies have investigated the effect of maternal vitamin D during pregnancy on offspring adiposity or cardiometabolic parameters with inconclusive results. OBJECTIVES The objective of this study is to examine the association of maternal 25(OH)-vitamin D [25(OH)D] status with offspring obesity and cardiometabolic characteristics in 532 mother-child pairs from the prospective pregnancy cohort Rhea in Crete, Greece. METHODS Maternal 25(OH)D concentrations were measured at the first prenatal visit (mean: 14 weeks, SD: 4). Child outcomes included body mass index standard deviation score, waist circumference, skin-fold thickness, blood pressure and serum lipids at ages 4 and 6 years. Body fat percentage was also measured at 6 years. Body mass index growth trajectories from birth to 6 years were estimated by mixed effects models with fractional polynomials of age. Adjusted associations were obtained via multivariable linear regression analyses. RESULTS About two-thirds of participating mothers had 25(OH)D concentrations

Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother–child pairs from the prospective pregnancy cohort, “Rhea” in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children’s Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity–impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p trend = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p trend = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (

BACKGROUND & AIMS: Vitamin D deficiency is common among pregnant women and may be associated with several adverse health outcomes including cancer. Micronuclei frequency is a biomarker of early genetic effects and has been used to examine the association between genotoxic exposures and cancer. We examined maternal vitamin D levels during pregnancy in associations with micronuclei frequency in maternal blood and in cord blood. METHODS: 173 mothers and 171 newborns born between 2007 and 2008 in Heraklion (Crete, Greece) were included in the study. Between 14th and 18th weeks of gestation we collected information on maternal diet using food frequency questionnaires (FFQs). We measured maternal serum concentrations of 25-hydroxyvitamin D [25(OH)D] between the first and second trimester of pregnancy. We estimated dietary vitamin D intake using information from FFQ. After delivery we collected cord blood and maternal peripheral blood. We used the cytokinesis-block micronucleus (CBMN) assay to assess the frequencies of micronucleated cells in binucleated T lymphocytes (MNBN). RESULTS: Maternal insufficient serum levels of 25(OH)D (

Introduction: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. Methods: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. Results: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9–31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3–49.1). Overall, DP was observed in 22.9% (95% CI 20.4–27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5–51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7–47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07–25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6–38.0) of patients and cabozantinib in 27.7% (95% CI 22.05–33.4). DP occurred in 23.7% (95% CI 19.9–27.6) with vandetanib use and in 22.6% (95% CI 17.4–27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. Conclusion: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.

Studies have suggested an association between maternal obesity pre-pregnancy and gestational diabetes (GDM) with impaired offspring neurodevelopment, but it is not clear if these associations are explained by shared familiar characteristics. We aimed to assess the associations of maternal and paternal obesity, maternal glucose intolerance in early pregnancy and GDM, with offspring neurodevelopment at 4 years of age. We included 772 mother–child pairs from the “Rhea” Mother–Child cohort in Crete, Greece. Data on maternal/paternal body mass index (BMI) and maternal fasting serum samples for glucose and insulin measurements were collected at 12 weeks of gestation. GDM screening was performed at 24–28 weeks. Neurodevelopment at 4 years was assessed using the McCarthy Scales of Children’s Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Multivariate linear regression analyses showed that maternal obesity was associated with a significant score reduction in general cognitive ability (β-coeff −4.03, 95% CI: −7.08, −0.97), perceptual performance (β-coeff −4.60, 95% CI: −7.74, −1.47), quantitative ability (β-coeff −4.43, 95% CI: −7.68, −1.18), and executive functions (β-coeff −4.92, 95% CI: −8.06, −1.78) at 4 years of age, after adjustment for several confounders and paternal BMI. Maternal obesity was also associated with increased behavioral difficulties (β-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (β-coeff 4.28, 95% CI: 1.20, 7.36) at preschool age. Paternal obesity maternal glucose intolerance in early pregnancy and GDM was not associated with child neurodevelopment. These findings suggest that maternal obesity may impair optimal child neurodevelopment at preschool age independently of family shared characteristics.

To describe a rare case of occult (1 cm in diameter) medullary thyroid carcinoma (MTC) in a 45-year-old woman, presenting as an asymptomatic mediastinal mass.The diagnostic methodology included laboratory measurements of relevant biochemical and hormonal parameters including calcitonin (CT), carcinoembryonic antigen (CEA) and chromogranin A, and imaging techniques including ultrasound (U/S), computed tomography (C/T), magnetic resonance imaging (MRI) and radio labeled somatostatin analog ((111)In-DTPA-octreotide).Chest CT revealed a mediastinal mass measuring 5 cm in diameter abutting the right thyroid lobe. CEA was elevated and an association with thyroid malignancies was considered. CT was found to be markedly elevated, pointing to the diagnosis of MTC metastatic to the mediastinum. The patient underwent total thyroidectomy, lymph node dissection and removal of the mediastinal mass. Histological examination revealed MTC of the right thyroid lobe measuring 0.5 cm, metastatic to regional and superior mediastinal lymph nodes.Occult MTC can infrequently present as an asymptomatic mediastinal mass. Elevated serum CT and CEA along with imaging techniques leads to the correct diagnosis and surgical management of the disease.

Estimation and interpretation of thyroid function tests in pregnant women is of utmost importance for maternal, fetal and neonatal health. Our objective was to calculate laboratory- and geography-specific reference intervals for thyroid hormones during pregnancy in an iodine-sufficient area of the Mediterranean, Crete, Greece. This project was performed in the context of “Rhea” mother-child cohort. Fulfillment of extensive questionnaires and estimation of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and antithyroid antibodies were performed. The reference population was defined using inclusion criteria regarding thyroidal, obstetric, and general medical status of women. Reference interval for TSH was 0.05–2.53 μIU/mL for the first and 0.18–2.73 μIU/mL for the second trimester. 6,8% and 5,9% of women in the first and second trimester, respectively, had TSH higher than the upper reference limit. These trimester-specific population-based reference ranges are essential in everyday clinical practice for the correct interpretation of thyroid hormone values and accurate classification of thyroid disorders.

CONTEXT: Maternal pre-pregnancy obesity may increase the risk of childhood obesity but it is unknown whether other metabolic factors in early pregnancy such as lipid profile and hypertension are associated with offspring cardiometabolic traits. OBJECTIVE: Our objective was to investigate whether fasting lipid, glucose, and insulin levels during early pregnancy and maternal pre-pregnancy weight status, are associated with offspring adiposity measures, lipid levels and blood pressure at preschool age. DESIGN AND METHODS: The study included 618 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. Pregnant women were recruited at the first prenatal visit (mean: 12weeks, SD: 0.7). A subset of 348 women provided fasting serum samples for glucose and lipid measurements. Outcomes measures were body mass index, abdominal circumference, sum of skinfold thickness, and blood pressure measurements at 4 years of age. A subsample of 525 children provided non-fasting blood samples for lipid measurements. RESULTS: Pre-pregnancy overweight/obesity was associated with greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81), central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10mmHg in diastolic blood pressure in early pregnancy was associated with increased risk of offspring overweight/obesity (RR: 1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71mm (95% CI: 0.57, 2.86) at 4 years of age./nCONCLUSIONS: Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age. Rhea project was financially supported by European projects (EU FP6-2003-Food-3- NewGeneris, EU FP6. STREP Hiwate, EU FP7 Rhea project was financially supported byEuropean projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7. ENV.2007.1.2.2.2. Project No 211250 Escape, EUFP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO,EU- FP7- HEALTH-2012 Proposal No 308333HELIX) and the Greek Ministry of Health (Program ofPrevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district,Crete, Greece: 2011-2014;“Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-15)

Objective The purpose of this study was to investigate the association of trimester-specific gestational weight gain with offspring fetal growth, obesity risk, and cardiometabolic health outcomes from birth to 4 years of age. Study Design We conducted the present study with 977 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. We measured birthweight, body mass index from 6 months to 4 years of age, waist circumference, skinfold thickness, blood pressure, and blood levels of lipids, C-reactive protein, and adipose tissue hormones at 4 years of age. We used multiple linear and log Poisson regression models to examine the association of exposure with continuous or binary outcomes, respectively. Results Greater rate of gestational weight gain in the first trimester of pregnancy (per 200 g/wk) was associated with increased risk of overweight/obesity from 2 years (relative risk [RR], 1.25; 95% confidence interval [CI], 1.09–1.42) to 4 years of age (RR, 1.15; 95% CI, 1.05–1.25), but not with birth size. Each 200 g/wk of weight gain in the first trimester of pregnancy was also associated with greater risk of high waist circumference (RR, 1.13; 95% CI, 1.04–1.23), high sum of skinfold thickness (RR, 1.15; 95% CI, 1.02–1.29), and higher diastolic blood pressure at 4 years of age (β, 0.43 mm Hg; 95% CI, 0.00–0.86). Greater rate of gestational weight gain during the second and third trimesters of pregnancy (per 200 g/wk) was associated with greater risk of large-for-gestational-age neonates (RR, 1.22; 95% CI, 1.02, 1.45) and higher levels of cord blood leptin (ratio of geometric means, 1.08; 95% CI, 1.00–1.17), but not with child anthropometry at later ages. Conclusion Timing of gestational weight gain may influence childhood cardiometabolic outcomes differentially.

Aim The objective of the present study was to determine whether or not maternal metabolic syndrome in early pregnancy in women without previous diabetes is associated with the development of gestational diabetes mellitus (GDM). Methods A total of 508 women from the Rhea study—involving a pregnant cohort in Crete, Greece (2007–2009)—with singleton pregnancies were included in the present analysis. Maternal fasting serum samples were collected and blood pressure measured before gestational week 15. The metabolic syndrome in early pregnancy was defined according to NHLBI/AHA criteria. Pregnant women were screened for GDM between weeks 24 and 28 of gestation, as defined by Carpenter and Coustan criteria. Multivariable log-binomial regression models were used to estimate the effect of the metabolic syndrome in early pregnancy on the risk of GDM, after adjusting for confounding factors. Results Women with the metabolic syndrome were at high risk of GDM (RR = 3.17; 95% CI: 1.06–9.50). Among the components of the metabolic syndrome, the most significant risk factors were impaired fasting glucose (RR = 4.92; 95% CI: 1.41–17.23) and pre-pregnancy obesity (RR = 2.65; 95% CI: 1.23–5.70). A 10-mmHg rise in systolic and diastolic blood pressure increased the relative risk of GDM by 49% (RR = 1.49; 95% CI: 1.10–2.02) and 34% (RR = 1.34; 95% CI: 1.04–1.73), respectively, whereas a 1-unit increase in pre-pregnancy BMI increased the relative risk of GDM by 6% (RR = 1.06; 95% CI: 1.01–1.12). Conclusion These findings suggest that women with the metabolic syndrome in early pregnancy have a greater risk of developing GDM.

The authors determined the association between metabolic syndrome in early pregnancy (mean, 11.96 weeks) and the risk of preterm birth in the mother-child cohort study (>Rhea> Study) in Crete, Greece, 2007-2009. Maternal fasting serum samples were collected, and blood pressure was measured at the time of the first major ultrasound examination (n=625). Multivariable log-binomial regression models were used. Women with metabolic syndrome were at high risk for preterm birth (relative risk (RR)=2.93, 95% confidence interval (CI): 1.53, 5.58), with the highest risk observed for medically indicated preterm births (RR=5.13, 95% CI: 1.97, 13.38). Among the components of metabolic syndrome, the most significant risk factor was hypertension (RR=2.32, 95% CI: 1.28, 4.20). An elevation of 10 mm Hg in diastolic blood pressure increased the relative risk for preterm birth by 29% (RR= 1.29, 95% CI: 1.08, 1.53), while a per unit increase in the low density lipoprotein/high density lipoprotein cholesterol ratio increased this risk by 19% (RR=1.19, 95% CI: 1.02, 1.39). Fetal weight growth restriction was associated with elevated levels of insulin (RR=1.14, 95% CI: 1.08, 1.20) and diastolic blood pressure (RR=1.27, 95% CI: 1.00, 1.61) in early pregnancy. These findings suggest that women with metabolic syndrome in early pregnancy had higher risk for preterm birth., This work was partly supported by the European Union Integrated Project NewGeneris, 6th Framework Program (contract FOOD-CT-2005-016320), and by the European Union-funded project HiWATE, 6th Framework Program (contract Food-CT-2006-036224).