Urinary iodine concentrations in preschoolers and cognitive development at 4 and 6 years of age, the Rhea mother-child cohort on Crete, Greece.

BACKGROUND: Evidence regarding child iodine intake and neurodevelopment is scarce. METHODS: We aimed to assess the impact of child iodine intake at 4 years of age on cognitive and motor development at 4 and 6 years among 304 children from the Rhea cohort on Crete, Greece. Child iodine intake was assessed via urinary iodine concentrations (UIC) measured using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and adjusted for specific gravity. Child cognitive and motor development was assessed using the McCarthy Scales of Children's Abilities (MSCA) at 4 years of age and Raven's Coloured Progressive Matrices (RCPM), Finger Tapping Test (FTT), and Trail Making Test (TMT) at 6 years. Associations were explored using multivariable-adjusted linear regression analyses with UIC categorized according to WHO criteria [insufficient intake <100 µg/L, adequate 100-299 µg/L (reference group), excessive ≥300 µg/L]. RESULTS: The children's median UIC was 249 µg/L (25-75th percentile: 181-344 µg/L). Children with UIC <100 µg/L had lower scores in the motor scale at 4 years (MSCA-motor scale: B=-10.3; 95 %CI -19.9, -0.6; n=10) and in intelligence at 6 years (RCPM-total score: B=-3.6, 95 %CI -6.8, -0.5; n=9) than children in the reference group. No associations were found with the general cognitive scale at 4 years or with TMT and FTT scales at 6 years. Children with UIC ≥300 µg/L had lower cognitive scores both at 4 (MSCA; B= -3.5; 95 %CI -6.9, -0.1; n =101) and 6 years of age (RCPM-total score; B= -1.2; 95 %CI -2.3, -0.0; n =98) than children in the reference group. No associations were observed with the motor scale at 4 years or with TMT and FTT scales at 6 years. CONCLUSION: Our findings indicate that both low and excessive iodine intake at preschool age may adversely affect child cognitive abilities. Additionally, low iodine intake may also impact motor abilities.

Thyroglobulin as a Rapid and Cost-Effective Biomarker for Diagnosis of Thyroid Carcinoma Brain Metastasis: A Case Report of a Patient with Metastatic Hurthle Cell Thyroid Carcinoma.

BACKGROUND Brain metastasis of papillary thyroid cancer (PTC) is rare. Treatment of these patients is challenging due to the lack of specific guidelines. Early diagnosis is accompanied by immediate treatment and less morbidity. Total resection of brain lesions may be unattainable when they include infiltration of eloquent areas. This report is of an 81-year-old man who had undergone total thyroidectomy for goiter in the past and presented with metastatic papillary thyroid carcinoma (PTC) to the neck after a gap of 16 years. After two years, the patient developed a solitary cystic brain PTC metastasis associated with raised thyroglobulin (Tg) inside the cystic lesion aspirated during brain surgery. CASE REPORT An 81-year-old male patient was admitted for a space-occupying brain lesion in the right frontal lobe. The patient's history included metastatic disease of PTC to the neck with cervical lymph node metastasis and local recurrence after surgery and radioactive iodine-131 treatment. The patient underwent craniotomy and removal of the lesion. The aspirated fluid was sent for cytological examination and measurement of Tg levels, which were interestingly high. Pathology of the brain lesion revealed infiltration of brain parenchyma from a metastatic lesion characterized by eosinophilic cells with irregular contours forming grooves, resulting in cytoplasmic pseudo-inclusions, an oncotic variant of PTC. CONCLUSIONS This report has shown that residual tissue may be present following total thyroidectomy and may be the origin of PTC with metastasis to the brain. The patient in this study suffered from a brain lesion that could be excised. However, aspiration of cystic compartments could provide a rapid diagnosis in patients with non-removable brain lesions.

Asymptomatic Bacteriuria in Patients with Type 2 Diabetes Mellitus.

Objectives: Asymptomatic bacteriuria (ASB) is a common finding in patients with diabetes. Moreover, patients with diabetes and ASB have a greater risk for symptomatic urinary tract infections and associated severe complications. The aim of this study was to estimate the prevalence of ASB, as well as to identify independent risk factors and related pathogens associated with ASB in female and male patients with type 2 diabetes mellitus (T2D). Methods: This prospective case-control study was performed at the University hospital, and the Venezeleion General Hospital, Heraklion, Greece between 2012 and 2019. All patients with T2D attending the diabetes and hypertension outpatient clinics at both hospitals were enrolled, and data regarding their medical history and clinical and laboratory profiles were recorded. Asymptomatic patients with positive urine cultures were assigned as cases while those with negative urine cultures were designated as controls. Results: A total of 437 adult patients of which 61% were female and 39% were male patients with a mean age of 70.5 ± 9.6 years, were enrolled. The prevalence of ASB was 20.1%, in total. ASB was noted in 27% of female participants and 9.4% of male participants. Higher glycated hemoglobin (OR = 3.921, 95%CI: 1.521−10.109, p < 0.001) and urinary tract infection within the previous year (OR = 13.254, 95%CI: 2.245−78.241, p < 0.001) were independently positively associated with ASB, while higher levels of vitamin B12 were independently negatively associated with ASB (OR = 0.994 per ng/mL, 95%CI: 0.989−0.999, p < 0.001). Conclusions: Development of ASB was associated with specific factors, some of which may be modifiable. Interestingly, high B12 was found to be negatively associated with ASB.

Association of maternal urinary fluoride concentrations during pregnancy with size at birth and the potential mediation effect by maternal thyroid hormones: The Swedish NICE birth cohort.

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.

C1q Gene Polymorphism Is Associated with Asymptomatic Bacteriuria in Patients with Type 2 Diabetes Mellitus.

Background and Objectives: Asymptomatic bacteriuria (ASB) appears to have a higher prevalence in diabetics and has been associated with various genetic polymorphisms of the innate immune system. Single nucleotide polymorphisms (SNPs) of the C1q gene that encodes for the trigger molecule of the classical complement pathway increase the risk of bacterial infections as well as other diseases. In the present study, we sought to investigate the association of C1q rs292001 (G > A) SNP with ASB in patients with type 2 diabetes (T2D). Materials and Methods: In this case-control study, performed at the University and the Venizeleion General Hospital of Heraklion, Crete, Greece, 75 adult male and female Cretan patients with T2D and ASB and 75 adult male and female Cretan patients with T2D but without ASB were enrolled and genotyped for rs292001 SNP of C1q gene. Genetic analysis was based on the polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RLFPs) methods. Results: Τhe frequency of homozygotes for the G/G genotype of C1q rs292001 was significantly higher in patients with T2D and ASB than in the control group (p-value = 0.0480, OR = 2.952, 95% CI: 1.052−7.542). Conclusions: Τhe present study provides the first evidence of an association between the C1q rs292001 SNP and an increased susceptibility for ASB in an adult Cretan population with T2D, thus suggesting that this SNP can be encountered as a risk factor for the presence of ASB in patients with T2D.

Associations of exposure to cadmium, antimony, lead and their mixture with gestational thyroid homeostasis.

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.

Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis.

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.

Association of the Interleukin-6 rs1800795 Polymorphism with Type 2 Diabetes Mellitus in the Population of the Island of Crete, Greece.

BACKGROUND: 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. MATERIALS AND METHODS: 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 -174G>C (rs1800795) SNP by the restriction fragment length polymorphism method. RESULTS: 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). CONCLUSION: 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.

Postoperative day 1 levels of parathyroid as predictor of occurrence and severity of hypocalcaemia after total thyroidectomy.

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.

High maternal vitamin D levels in early pregnancy may protect against behavioral difficulties at preschool age: the Rhea mother-child cohort, Crete, Greece.

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 (<38.4 nmol/l), after adjustment for several confounders. Similar associations were found with the hyperactivity/inattention score of the SDQ questionnaire. Children of mothers with high 25(OH) D levels had also fewer total behavioral difficulties (beta-coeff: -1.25, 95% CI -2.32, -0.19) and externalizing symptoms (beta-coeff: -0.87, 95% CI -1.58, -0.15) at preschool age. The observed associations were stronger in girls than in boys (p for interaction < 0.1). No association was observed between maternal 25(OH) D concentrations and cognitive function in preschoolers. Our results suggest that high maternal vitamin D levels in early pregnancy may protect against behavioral difficulties, especially ADHD-like symptoms at preschool age.

Maternal diet during pregnancy and micronuclei frequency in peripheral blood T lymphocytes in mothers and newborns (Rhea cohort, Crete).

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.

Effect of parental obesity and gestational diabetes on child neuropsychological and behavioral development at 4 years of age: the Rhea mother-child cohort, Crete, Greece.

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 (ß-coeff -4.03, 95% CI: -7.08, -0.97), perceptual performance (ß-coeff -4.60, 95% CI: -7.74, -1.47), quantitative ability (ß-coeff -4.43, 95% CI: -7.68, -1.18), and executive functions (ß-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 (ß-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (ß-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.

Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete).

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 (<50 nmol/L) during pregnancy were associated with increased MNBN frequency in cord blood [IRR = 1.32 (95%CI: 1.00, 1.72)]. This increase was higher for newborns with birth weight above the third quartile [≥3.500 kg; IRR = 2.21 (1.26, 3.89)]. Similarly, low levels of dietary vitamin D were associated with increased MNBN frequency in cord blood [middle tertile IRR = 1.08 (0.78, 1.47), lower tertile IRR = 1.51 (1.06, 2.14)]. Insufficient levels of vitamin D were not associated with MNBN in mothers. CONCLUSION: Our results suggest that vitamin D deficiency during pregnancy increases genotoxic risks in newborns. The prevalence of vitamin D deficiency globally is high and it is important to further investigate whether vitamin D supplementation or similar interventions during pregnancy could prevent DNA damage at early stages of life.

Metabolic profile in early pregnancy is associated with offspring adiposity at 4 years of age: the Rhea pregnancy cohort Crete, Greece.

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: 12 weeks, 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 5.10 mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40 mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30 mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10 mmHg 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 1.71 mm (95% CI: 0.57, 2.86) at 4 years of age. CONCLUSIONS: Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.

Association of trimester-specific gestational weight gain with fetal growth, offspring obesity, and cardiometabolic traits in early childhood.

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 (ß, 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.

Rare presentation of occult medullary carcinoma of the thyroid as a mediastinal mass.

OBJECTIVE: 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. DESIGN: 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). RESULTS: 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. CONCLUSIONS: 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.

First- and Second-Trimester Reference Intervals for Thyroid Hormones during Pregnancy in "Rhea" Mother-Child Cohort, Crete, Greece.

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.

Metabolic syndrome in early pregnancy and risk of preterm birth.

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.