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THE POST-PARTUM PERIOD IS A PERIOD OF SIGNIFICANT MATERNAL FRAGILITY FOLLOWING PHYSI-CAL, HORMONAL, PSYCHOLOGICAL AND SOCIAL CHANGES. POST-PARTUM DEPRESSION HAS A PREVA-LENCE RATE OF 10 TO 18%. THE INCIDENCE OF THYROID IMBALANCE IS HIGH IN THIS PERIOD DUE TO THE IMPACT OF PREGNANCY ON AUTOIMMUNITY, POINTED OUT AS A FREQUENT CAUSE IN A VARIETY OF THYROID ILLNESSES. WHEN BOTH COEXIST, THIS MAY RESULT IN A COMPLEX CLINICAL SITUATION, PROMPTING DIFFERENT HEALTH CARE PROFESSIONALS TO WORK TOGETHER. WE RE-VIEWED THE LITERATURE CONCERNING THE RELATIONSHIP BETWEEN THYROID FUNCTION (MORE SPECIFICALLY HYPERTHYROIDISM) AND PSYCHIATRIC SYMPTOMS, CLARIFYING THE ORIGIN OF THE DETERMINERS OF PSYCHIATRIC SYMPTOMS IN A MIXED ENDOCRINE-PSYCHIATRIC CLINICAL PRES-ENTATION IN PERINATAL PERIOD. WE, THEN, HIGHLIGHTED THE MULTIDISCIPLINARY TREATMENT COURSE, BASED ON THE LEARNINGS OF REFERENTIAL TEXTS REGARDING THE PERINATAL PERIOD. [ABSTRACT FROM AUTHOR]

Background: Resistance to thyroid hormone (RTH) is a rare thyroid disorder characterized by elevated free thyroid hormones with non-suppressed thyrotropin (TSH). Guidelines for the management of pregnancy in patients with RTH are not well defined. Chorionic villus biopsy is sometimes proposed to manage treatment based on the genotype of the fetus. Patient findings: A woman with RTH (c1243C>T, pR320C mutation in the thyroid hormone receptor β ( THRB gene)) associated with Hashimoto's thyroiditis (HT) had three successful pregnancies. During the pregnancies, the mother was treated with levothyroxine (LT4). She never underwent chorionic villus sampling. The babies had normal birth weights. The first child harbored the THRB mutation. Summary and conclusions: The management of pregnancies in patients with RTH and the indication for chorionic villus sampling are discussed in these cases. In RTH patients, pregnancies must be planned and closely followed. There is no need for prenatal diagnosis of RTH if the patient, due to limited thyroidal reserve, cannot produce excess of thyroid hormones to harm a normal fetus. The more common challenge in RTH remains how to best manage high maternal thyroid hormone levels, and whether or not to lower thyroid hormone levels based on the genotype of the fetus. [ABSTRACT FROM AUTHOR]

Calcitonin (Ct) is a tumour marker essential for the diagnosis and follow-up of medullary thyroid cancer (MTC). Accurate and consistent measurements of serum Ct are of critical importance. Ct measurements by different methods can differ, leading to difficulties in the interpretation of results. Second generation assays for Ct have been developed and are now available in clinical laboratories. However, the lack of standardization for Ct assays remains a common problem with Ct assays. The reference interval and reliability should be carefully defined. The role of stimulated Ct for the diagnosis and follow-up of MTC should also be pointed out as the pentagastrin test is no more available in all countries. However, the stimulated test remains very useful to exclude MTC if the basal Ct serum level is in the grey zone (15-20 ng/L), after surgery to confirm the complete cure. A residual response after surgery could indicate a need for aggressive surgery or - in case of metastatic disease - could suggest the prognosis. High-dose Ca test (2.5mg/kg) seems to be a reliable and effective test for the diagnosis and follow-up of MTC. It seems more potent than pentagastrin with fewer side effects. The threshold able to discriminate healthy subjects from C-cell hyperplasia (CCH) cases for the stimulated Ct concentration is 184 ng/L for women and 1620 ng/L for men. As stimulated Ca test will eventually replace the pentagastrin test, there is a need to confirm or to modify the threshold identified for each assay individually. [ABSTRACT FROM AUTHOR]

Focuses on the regulating mechanisms of endocytic catalysts Rab5a and Rab7 on thyroid hormone production. Information on rab proteins; Details on the expression level and membrane recruitment of the endocytic catalysts; Analysis of rab protein concentrations in adenomas.

Background: Despite notable progress in the fight against iodine deficiency disorders in the Democratic Republic of Congo, a recent study has shown that pregnant women in Lubumbashi were still iodine deficient. Our objective was to assess thyroid function in this population. Methods: In a cross-sectional study conducted in maternity units from three different socioeconomic areas in Lubumbashi, serum thyrotropin, free thyroxine, thyroglobulin, and thyroperoxidase antibodies were measured in 225 pregnant women attending antenatal visits, in 75 women who recently delivered, and in 75 nonpregnant controls. The outcome was the prevalence of thyroid dysfunction. Results: Median values in pregnant women, women who recently delivered, and nonpregnant women were 1.80, 2.80, and 1.54 mIU/L for thyrotropin ( p<0.001); 0.85, 1.11, and 1.16 ng/dL for free thyroxine ( p<0.001); and 13.3, 9.5, and 10.4 ng/mL for thyroglobulin ( p=0.01), respectively. The prevalence of thyroid dysfunction in pregnant women, in women who recently delivered, and in nonpregnant women was 31%, 8%, and 20% for isolated hypothyroxinemia ( p<0.001); 12%, 24%, and 5% for subclinical hypothyroidism ( p=0.002); 8%, 3%, and 3%, for overt hypothyroidism ( p=0.09); and 5%, 13%, and 4%, for positive thyroperoxidase antibodies ( p=0.03), respectively. In multiple logistic regression, women who were pregnant or who recently delivered, who lived in a poor socioeconomic area, and who had low urinary iodine concentration were more likely to have an increased serum thyrotropin: odds ratio (OR)=3.43 (95% confidence interval [CI] 1.23-9.53) for pregnancy, OR=4.49 [CI 1.66-15.01] for postpartum period, OR=3.68 [CI 1.85-7.35] for semiurban area, and OR=0.44 [CI 0.19-0.96] for urinary iodine concentration ≥250 μg/L. Conclusions: Our results show that there is a high prevalence of thyroid dysfunction in pregnant women of Lubumbashi, and this high prevalence is associated with iodine deficiency. To prevent obstetrical adverse outcomes and neurological damage in children, iodine supplementation is needed before conception or in early pregnancy in Lubumbashi. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available. Method: Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys. Results: Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms. Conclusions: LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit. [ABSTRACT FROM AUTHOR]

Background: Even though the clinical features of Graves' orbitopathy (GO) are well known, its exact pathogenesis remains controversial. The imbalance of redox homeostasis in the connective tissue could play a crucial role leading to an inflammatory state and edema of soft orbital tissues, thus contributing to orbital hypoxia and increase in hypoxia-inducible factor (HIF)-1α. This oxidative stress appears to target the orbital cells such as fibroblasts and also adipocytes. This study aims to explore which pathways can lead to the aforementioned oxidative stress in GO adipose cells and therefore offers new plausible therapeutic targets. Methods: Orbital fat samples were obtained from patients with GO (Western blot [WB]: n = 8, immunohistochemistry [IHC]: n = 8) and from control patients (WB: n = 5, IHC: n = 3–5). They were processed for WB analysis and IHC of the antioxidants (catalase, superoxide dismutase 1) and for HIF-1α. The expression of caveolin-1 (Cav-1) and deiodinase 3 (DIO3), known to be regulated by HIF-1α, was also analyzed by WB and IHC, as well as the targets of Cav-1: glucose transporter type 4 (Glut-4), NADPH oxidase (NOX)-2, and endothelial nitric oxide synthase (eNOS). Triiodothyronine (T3) expression was also analyzed by IHC. Results: In GO adipocytes, the expression of catalase was reduced, whereas that of HIF-1α was strongly increased. A decreased local T3 supply was associated with DIO3 upregulation. The low expression of Cav-1 in GO adipocytes was associated not only with low expression of Glut-4 but also with an increased expression of NOX-2 and active eNOS phosphorylated on serine 1177. Conclusions: Cav-1 and DIO3, both sensitive to hypoxia and to the increase of HIF-1α, play a pivotal role in the oxidative stress in GO adipocytes. DIO3 regulates the cellular supply of T3, which is essential for the cell homeostasis. Cav-1 determines the cellular glucose supply through Glut-4 and regulates the activity of NOX-2 generating superoxide anions and that of eNOS generating nitric oxide (NO). [ABSTRACT FROM AUTHOR]

Objective: To construct a predictive score for the development or progression of Graves' orbitopathy (GO) in Graves' hyperthyroidism (GH). Design: Prospective observational study in patients with newly diagnosed GH, treated with antithyroid drugs (ATD) for 18 months at ten participating centers from EUGOGO in 8 European countries. Methods: 348 patients were included with untreated GH but without obvious GO. Mixed effects logistic regression was used to determine the best predictors. A predictive score (called PREDIGO) was constructed. Results: GO occurred in 15% (mild in 13% and moderate to severe in 2%), predominantly at 6-12 months after start of ATD. Independent baseline determinants for the development of GO were clinical activity score (assigned 5 points if score > 0), TSH-binding inhibitory immunoglobulins (2 points if TBII 2-010 U/L, 5 points if TBII > 10 U/L), duration of hyperthyroid symptoms (1 point if 1-4 months, 3 points if >4 months) and smoking (2 points if current smoker). Based on the odds ratio of each of these four determinants, a quantitative predictive score (called PREDIGO) was constructed ranging from 0 to 15 with higher scores denoting higher risk; positive and negative predictive values were 0.28 (95% CI 0.20-0.37) and 0.91 (95% CI 0.87-0.94) respectively. Conclusions: In patients without GO at diagnosis, 15% will develop GO (13% mild, 2% moderate to severe) during subsequent treatment with ATD for 18 months. A predictive score called PREDIGO composed of four baseline determinants was better in predicting those patients who will not develop obvious GO than who will. [ABSTRACT FROM AUTHOR]

Background Isolated maternal hypothyroxinaemia ( IH) is defined as low maternal FT4 (<5th percentile) and normal thyroid-stimulating hormone. There is concern on its potential negative effects on the mother and offspring. Objective We aimed to evaluate the prevalence of IH and to assess the consequences of hypothyroxinaemia on the maternal and foetal outcomes. Subjects and methods From a total of 1300 consecutive pregnant women recruited during the prenatal screen (mean gestational age, 11·8 weeks), thyroid function parameters were assessed in 879 women. After exclusion of women with T4 supplements, with twin pregnancies and with diabetes, data from 783 women were included. Maternal and neonatal outcomes in 55 selected women with IH and negative thyroid auto-antibodies without thyroid disorders or pregnancy achieved through assisted reproductive techniques were compared with a selected euthyroid control group ( N = 165). Results Among the 783 non diabetic singleton pregnant women, 68 women (8·7%) were identified with IH. When compared to the selected euthyroid controls, selected women with hypothyroxinaemia had significantly increased body mass index ( BMI) in preconception ( P = 0·003), in the first trimester ( P = 0·004) and at the time of delivery ( P = 0·001). At term, foetal breech presentation and caesarean section rate were significantly higher ( P = 0·006 and P = 0·026, respectively) than in the euthyroid controls. A significant increase in macrosomia was also noted ( P = 0·026). Conclusion The prevalence of hypothyroxinaemia in early pregnancy was of 8·7%. IH is associated with an increased maternal BMI and is related with a risk of breech presentation, a significant increase in macrosomia and caesarean sections. Screening should consider overweight as risk factor for hypothyroxinaemia. [ABSTRACT FROM AUTHOR]

Background: Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates the expression of multiple target genes involved in several metabolic pathways as well as in inflammation. The expression and cell localization of caveolin-1 (Cav-1), thyroperoxidase (TPO), and dual oxidase (DUOX), involved in extracellular iodination, is modulated by Th1 cytokines in human normal thyroid cells and in Hashimoto's thyroiditis (HT). Objectives: The objectives of this study were (i) to analyze the PPARγ protein and mRNA expression at the follicular level in HT versus controls in correlation with the one of Cav-1; (ii) to study the effects of Th1 cytokines on PPARγ and catalase expression in human thyrocyte primary cultures; and (iii) to study the effects of pioglitazone, a PPARγ agonist, on thyroxisome components (Cav-1, TPO, DUOX) and on catalase, involved in antioxidant defense. Results: Although the global expression of PPARγ in the whole gland of patients with HT was not modified compared with controls, there was great heterogeneity among glands and among follicles within the same thyroid. Besides normal (type 1) follicles, there were around inflammatory zones, hyperactive (type 2) follicles with high PPARγ and Cav-1 expression, and inactive (type 3) follicles which were unable to form thyroxine and did not express PPARγ or Cav-1. In human thyrocytes in primary culture, Th1 cytokines decreased PPARγ and catalase expression; pioglitazone increased Cav-1, TPO, and catalase expression. Conclusion: PPARγ may play a central role in normal thyroid physiology by upregulating Cav-1, essential for the organization of the thyroxisome and extracellular iodination. By upregulating catalase, PPARγ may also contribute to cell homeostasis. The inhibitory effect of Th1 cytokines on PPARγ expression may be considered as a new pathogenetic mechanism for HT, and the use of PPARγ agonists could open a new therapeutic approach. [ABSTRACT FROM AUTHOR]

Background/aims The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. Methods Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. Results The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 ( p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). Conclusions These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe. [ABSTRACT FROM AUTHOR]

Background: Graves' orbitopathy (GO) is the main extrathyroidal manifestation associated with Graves' disease (GD). It is characterized by reduced eye motility due to an increased volume of orbital fat and/or of extraocular muscles (EOMs) infiltrated by fibrosis and adipose tissue. The pathogenetic mechanisms leading to fibrosis and adipogenesis are mainly based on the interaction between orbital fibroblasts and immune cells (lymphocytes and mast cells) infiltrating the GO EOMs. Methods: Analysis of the morphological status, oxidative stress (OS), and antioxidant defenses in the orbital muscular cells and adipocytes in GO patients compared with controls was conducted. Results: Both cell types are affected by OS, as shown by the increased expression of 4-hydroxynonenal, which leads to apoptosis in muscular cells. However, the EOMs and the adipocytes possess antioxidant defenses (peroxiredoxin 5 and catalase) against the OS, which are also upregulated in thyrocytes in GD. The expression of adiponectin (ApN) and proliferator-activated receptor gamma (PPARγ) is also increased in GO muscular cells and adipocytes. OS and antioxidant proteins expression are correlated to the level of blood antithyrotropin receptor antibodies (TSHR-Ab). Conclusion: Even when TSHR-Ab level is normalized, OS and antioxidant protein expression is high in EOM muscular cells and adipocytes in GO compared with controls. This justifies a supplementation with antioxidants in active as well as chronic GO patients. Orbital muscular cells are also the sources of PPARγ and ApN, which have direct or indirect local protective effects against OS. Modulation of these proteins could be considered as a future therapeutic approach for GO. [ABSTRACT FROM AUTHOR]

ObjectiveAdequate iodine and Fe intakes are imperative during pregnancy to prevent fetal defects, but such data are not available in the Democratic Republic of Congo. We aimed to assess iodine and Fe status in pregnant women from Lubumbashi.DesignCross-sectional study. We measured urinary iodine concentration (UIC) in random urine samples using a modified Sandell–Kolthoff digestion method; the WHO reference medians were used to classify iodine intake as deficient, adequate, more than adequate or excessive. Serum ferritin concentrations were measured by immunoenzymatic assay and considered insufficient when <12 ng/ml.SettingMaternity units from rural, semi-urban and urban areas of Lubumbashi, Democratic Republic of Congo.SubjectsTwo hundred and twenty-five randomly selected pregnant women attending prenatal consultation, seventy-five postpartum women and seventy-five non-pregnant women as controls.ResultsOverall median UIC in pregnant women was 138 (interquartile range: 105–172) μg/l, indicating iodine deficiency, whereas postpartum and non-pregnant women had adequate iodine intake: median UIC = 144 μg/l and 204 μg/l, respectively. Median UIC values were lower in late pregnancy than in early pregnancy: in the first, second and third trimester respectively 255 μg/l, 70 μg/l and 88 μg/l in the rural area; 306 μg/l, 166 μg/l and 68 μg/l in the semi-urban area; and 203 μg/l, 174 μg/l and 99 μg/l in the urban area. Fe was insufficient in 39 % of pregnant women compared with 21 % of non-pregnant and postpartum women. In the third trimester, deficiencies in both iodine and Fe were high: 40 %, 12 % and 18 % in the rural, semi-urban and urban areas, respectively.ConclusionsOur data suggest that pregnant women are at risk of iodine and Fe deficiencies in Lubumbashi. Country policies fighting against iodine and Fe deficiencies during pregnancy should be reinforced. [ABSTRACT FROM AUTHOR]

Background/Aims: Universal screening for thyroid diseases during pregnancy is controversial. Targeted screening does not identify all women with thyroid dysfunction. Furthermore, antithyroid peroxidase antibodies (TPOAb) are suspected to be associated with an increased risk of fetal loss, premature delivery and hypothyroidism. The aim of our study was to assess the rationale behind universal screening and propose thyroxine treatment in particular cases. Methods: Between January 2008 and May 2009,537 consecutive iodine-supplemented women with a singleton pregnancy [441 TPOAb-controls and 96 TPOAb+ women (47 nontreated and 49 treated)] were evaluated using thyroid and obstetric parameters. According to our algorithm for thyroid screening in pregnancy, if thyroid-stimulating hormone (TSH) exceeded 1 mU/l in TPOAb+ women, 50µg of levothyroxine (L-T4) was prescribed. Results: The miscarriage rate was significantly higher in the nontreated TP0Ab+ group compared with the treated group (16 vs. 0%; p = 0.02). Compared to the control group, TSH in TPOAb+ patients was higher at the first prenatal visit prior to L-T4 treatment (p < 0.01), while free thyroxine was higher than in the control group after the 20th week (p <0.05). Conclusions: Our study supports the potential benefit of universal screening and L-T4 treatment for autoimmune thyroid disease during pregnancy. Efforts are still needed to further decrease miscarriage rates. [ABSTRACT FROM AUTHOR]

Graves' disease (GD) is an autoimmune thyroiditis often associated with Graves' orbitopathy (GO). GD thyroid and GO orbital fat share high oxidative stress (OS) and hypervascularization. We investigated the metabolic pathways leading to OS and angiogenesis, aiming to further decipher the link between local and systemic GD manifestations. Plasma and thyroid samples were obtained from patients operated on for multinodular goiters (controls) or GD. Orbital fats were from GO or control patients. The NADPH-oxidase-4 (NOX4)/HIF-1α/VEGF-A signaling pathway was investigated by Western blotting and immunostaining. miR-199a family expression was evaluated following quantitative real-time PCR and/or in situ hybridization. In GD thyroids and GO orbital fats, NOX4 was upregulated and correlated with HIF-1α stabilization and VEGF-A overexpression. The biotin assay identified NOX4, HIF-1α and VEGF-A as direct targets of miR-199a-5p in cultured thyrocytes. Interestingly, GD thyroids, GD plasmas and GO orbital fats showed a downregulation of miR-199a-3p/-5p. Our results also highlighted an activation of STAT-3 signaling in GD thyroids and GO orbital fats, a transcription factor known to negatively regulate miR-199a expression. We identified NOX4/HIF-1α/VEGF-A as critical actors in GD and GO. STAT-3-dependent regulation of miR-199a is proposed as a common driver leading to these events in GD thyroids and GO orbital fats. [ABSTRACT FROM AUTHOR]

In Hashimoto's thyroiditis (HT), oxidative stress (OS) is driven by Th1 cytokines' response interfering with the normal function of thyrocytes. OS results from an imbalance between an excessive production of reactive oxygen species (ROS) and a lowering of antioxidant production. Moreover, OS has been shown to inhibit Sirtuin 1 (SIRT1), which is able to prevent hypoxia-inducible factor (HIF)-1α stabilization. The aims of this study were to determine the involvement of NADPH-oxidases (NOX), SIRT1, and HIF-1α in HT pathophysiology as well as the status of antioxidant proteins such as peroxiredoxin 1 (PRDX1), catalase, and superoxide dismutase 1 (SOD1). The protein expressions of NOX2, NOX4, antioxidant enzymes, SIRT1, and HIF-1α, as well as glucose transporter-1 (GLUT-1) and vascular endothelial growth factor A (VEGF-A), were analyzed by Western blot in primary cultures of human thyrocytes that were or were not incubated with Th1 cytokines. The same proteins were also analyzed by immunohistochemistry in thyroid samples from control and HT patients. In human thyrocytes incubated with Th1 cytokines, NOX4 expression was increased whereas antioxidants, such as PRDX1, catalase, and SOD1, were reduced. Th1 cytokines also induced a significant decrease of SIRT1 protein expression associated with an upregulation of HIF-1α, GLUT-1, and VEGF-A proteins. With the exception of PRDX1 and SOD1, similar results were obtained in HT thyroids. OS due to an increase of ROS produced by NOX4 and a loss of antioxidant defenses (PRDX1, catalase, SOD1) correlates to a reduction of SIRT1 and an upregulation of HIF 1α, GLUT-1, and VEGF-A. Our study placed SIRT1 as a key regulator of OS and we, therefore, believe it could be considered as a potential therapeutic target in HT. [ABSTRACT FROM AUTHOR]