Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

First trimester isolated maternal hypothyroxinaemia: adverse maternal metabolic profile and impact on the obstetrical outcome.

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.

Antenatal thyroid screening and childhood cognitive function.

BACKGROUND: Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. METHODS: We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T(4)). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T(4) levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 µg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. RESULTS: Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], -1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, -2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. CONCLUSIONS: Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age. (Funded by the Wellcome Trust UK and Compagnia di San Paulo, Turin; Current Controlled Trials number, ISRCTN46178175.).

Management of patients with Graves' orbitopathy: initial assessment, management outside specialised centres and referral pathways.

Graves' orbitopathy (GO) is uncommon, but responsible for considerable morbidity. A coordinated approach between healthcare professionals is required in order to meet the needs of patients. Early diagnosis can be achieved by a simple clinical assessment. Low-cost effective interventions can be initiated by generalists, which may improve outcomes. Moderate-to-severe GO should be referred to specialised centres. Recommendations for clinical diagnosis, initial management and referral pathways are highlighted.

The importance of iodine in public health.

Iodine (I) deficiency has been known for more than a century and is known to cause cretinism at the extreme end of the spectrum but also, importantly, impaired development and neurocognition in areas of mild deficiency. The WHO has indicated that median urinary iodine of 100-199 µg/l in a population is regarded as indicative of an adequate iodine intake. The understanding of the spectrum of iodine deficiency disorders led to the formation of The International Council for the Control of Iodine Deficiency Disorders which has promulgated the use of household iodized salt and the use of such salt in food processing and manufacture. Iodine deficiency is particularly important in pregnancy as the fetus relies on maternal thyroxine (T4) exclusively during the first 14 weeks and also throughout gestation. As this hormone is critical to brain and nervous system maturation, low maternal T4 results in low child intelligence quotient. The recommendation for I intake in pregnancy is 250 µg/day to prevent fetal and child brain function impairment. During the past 25 years, the number of countries with I deficiency has reduced to 32; these still include many European developed countries. Sustainability of adequate iodine status must be achieved by continuous monitoring and where this has not been performed I deficiency has often recurred. More randomized controlled trials of iodine supplementation in pregnancy are required in mild iodine-deficient areas to inform public health strategy and subsequent government action on suitable provision of iodine to the population at risk.

Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on adolescent brain morphology.

CONTEXT: Children born to mothers with gestational hypo- or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear. OBJECTIVE: To establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF). DESIGN AND SETTING: The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from ∼12 weeks' gestation. At age 9, children born to mothers who were over-treated with levothyroxine had a higher risk of conduct and hyperactivity traits. For the current CATS III study, children underwent neuroimaging studies, including T1-weighted structural magnetic resonance imaging (MRI). PARTICIPANTS: A total of 85 children aged 11-16 years had usable T1-weighted MRI data (exposed to untreated SGTF (n=21), normal GTF (n=24), or treated SGTF (optimally-treated (n=21), over-treated (n=20)). MAIN OUTCOME MEASURES: Primary outcome: to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes: to investigate the association of maternal TSH and free T4 levels with global and subregional brain volumes. Results were adjusted for age, sex and pubertal scores. RESULTS: There were no significant differences in global brain volumetric measures between groups, including total gray matter volume (p=0.373). Weak positive correlations were found between maternal TSH, but not FT4, levels and several brain volumes, but these did not survive testing for multiple comparisons. CONCLUSIONS: We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no impact of levothyroxine supplementation.

Iodine status of UK schoolgirls: a cross-sectional survey.

BACKGROUND: Iodine deficiency is the most common cause of preventable mental impairment worldwide. It is defined by WHO as mild if the population median urinary iodine excretion is 50-99 µg/L, moderate if 20-49 µg/L, and severe if less than 20 µg/L. No contemporary data are available for the UK, which has no programme of food or salt iodination. We aimed to assess the current iodine status of the UK population. METHODS: In this cross-sectional survey, we systematically assessed iodine status in schoolgirls aged 14-15 years attending secondary school in nine UK centres. Urinary iodine concentrations and tap water iodine concentrations were measured in June-July, 2009, and November-December, 2009. Ethnic origin, postcode, and a validated diet questionnaire assessing sources of iodine were recorded. FINDINGS: 810 participants provided 737 urine samples. Data for dietary habits and iodine status were available for 664 participants. Median urinary iodine excretion was 80·1 µg/L (IQR 56·9-109·0). Urinary iodine measurements indicative of mild iodine deficiency were present in 51% (n=379) of participants, moderate deficiency in 16% (n=120), and severe deficiency in 1% (n=8). Prevalence of iodine deficiency was highest in Belfast (85%, n=135). Tap water iodine concentrations were low or undetectable and were not positively associated with urinary iodine concentrations. Multivariable general linear model analysis confirmed independent associations between low urinary iodine excretion and sampling in summer (p<0·0001), UK geographical location (p<0·0001), low intake of milk (p=0·03), and high intake of eggs (p=0·02). INTERPRETATION: Our findings suggest that the UK is iodine deficient. Since developing fetuses are the most susceptible to adverse effects of iodine deficiency and even mild perturbations of maternal and fetal thyroid function have an effect on neurodevelopment, these findings are of potential major public health importance. This study has drawn attention to an urgent need for a comprehensive investigation of UK iodine status and implementation of evidence-based recommendations for iodine supplementation. FUNDING: Clinical Endocrinology Trust.

Modelling the contribution of iodised salt in industrially processed foods to iodine intake in Macedonia.

Evidence from the 1950s showed that Macedonia was iodine deficient. After the introduction of mandatory universal salt iodisation, the country saw a steady increase in iodine intake and decline in goitre prevalence, earning iodine-deficiency free status in 2003. Iodine status assessments in 2007 and 2016 showed adequate iodine intake among school age children (median urinary iodine concentration of 241 µg/L and 236 µg/L respectively). Macedonia participated in piloting the Iodine Global Network Programme Guidance on the use of iodised salt in industrially processed foods to better understand potential iodised salt intake from processed foods. One objective of implementation was to identify the need, opportunities, and required actions to strengthen the processed food component of the national salt iodisation policy. Data from the 2017 Household Consumption and Expenditure Survey (HCES) was used to determine household salt consumption, to identify widely-consumed, salt-containing industrially processed foods, and estimate typical daily intake of these foods. Their estimated contribution to iodine intake was estimated based on their salt content and the percentage of food industry salt that is iodised. Although the study has limitations, including a relatively small selection of foods, the results indicate potential iodine intake from iodised household salt and iodised salt in the selected foods of nearly 300% of the Estimated Average Requirement and over 220% of the Recommended Nutrient Intake for adults. This was approximately 50% of the tolerable safe Upper Level for iodine intake. The study confirmed high daily salt intake (11.2 grams from household salt only). Successful salt reduction would be expected to reduce iodine intake, however, modelling with 10% and 30% reduction implied this is unlikely to put any population group at risk of deficiency. It is recommended that implementation of salt iodisation and salt reduction policies are harmonized, alongside continued regular iodine status monitoring for different population groups.

A systematic review of iodine intake in children, adults, and pregnant women in Europe-comparison against dietary recommendations and evaluation of dietary iodine sources.

CONTEXT: Adequate iodine intake is essential throughout life. Key dietary sources are iodized salt and animal products, but dietary patterns in Europe are changing, for example toward lower salt intake and a more plant-based diet. OBJECTIVE: To review iodine intake (not status) in European populations (adults, children, and pregnant women) to identify at-risk groups and dietary sources. DATA SOURCES: PubMed, Embase, and Cochrane databases, as well as European national nutrition surveys were searched for data on had iodine intake (from dietary assessment) and sources of iodine, collected after 2006. DATA SELECTION: In total, 57 studies were included, comprising 22 national surveys and 35 sub-national studies. Iodine intake data were available from national surveys of children aged <10 years (n = 11), 11-17 years (n = 12), and adults (n = 15), but data from pregnancy were only available from sub-national studies. RESULTS: Iodine intake data are lacking-only 17 of 45 (38%) European countries had iodine-intake data from national surveys. Iodine intake reported from national surveys was below recommendations for: (1) children aged <10 years in 2 surveys (18%), (2) boys and girls aged 11-17 years in 6 (50%) and 8 (68%) surveys, respectively, and (3) adult men and women in 7 (47%) and 12 (80%) surveys, respectively. In pregnant women, intake was below recommendations except where women were taking iodine-containing supplements. Just 32% of national surveys (n = 7) included iodized salt when estimating iodine intake. Milk, dairy products, fish, and eggs were important contributors to intake in many countries, suggesting limited sources in plant-based diets. CONCLUSION: Results are limited by the challenges of dietary assessment for measuring iodine intake. Future national surveys should include iodine intake. Policy makers should consider dietary sources alongside any iodized salt policies when considering methods for improving population iodine intake. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017 CRD42017075422.

Thyroid function in pregnancy.

Advances in understanding the physiology of thyroid function in normal pregnancy have highlighted the importance of the consequences of abnormal function on obstetric outcome and foetal well-being. Pubmed search was done using the terms thyroid and pregnancy. Areas of agreement are the following: gestational normative reference ranges for thyroid function tests are required for proper interpretation of any abnormalities. Measurement of thyroid-stimulating antibodies and antithyroid peroxidase antibodies is useful for diagnosis of thyroid disease in pregnancy. Treatment of Graves' hyperthyroidism should be done with propylthiouracil for first trimester only, then carbimazole or methimazole. Patients on levothyroxine require an increase in dosage during gestation. Areas of controversy are the following: total thyroxine (TT4) versus Free T4 (FT4) assays in pregnancy. Screening for thyroid function in early gestation: should it be routinely performed on everyone? What tests are appropriate? Growing points are the following: physiology of thyroxine delivery to the foetus. Establishment of gestational thyroid hormone reference ranges. Evaluation of strategies to screen thyroid function in early pregnancy. Areas timely for developing research are the following: placental thyroid hormone physiology, thyroid hormone therapy and screening thyroid function.

Thyroid Autoimmunity and Dysfunction in Sri Lankan Children and Adolescents After 22 Years of Sustained Universal Salt Iodization.

Background: Sri Lanka introduced universal salt iodization (USI) in 1995 after which we demonstrated a high thyroglobulin antibody (TgAb) prevalence in 1998. However, it is unclear whether thyroid autoimmunity persists in the long term in populations exposed to sustained USI and whether such populations have an excess of thyroid dysfunction. We evaluated the prevalence of thyroid autoantibodies and dysfunction in Sri Lankan children and adolescents after more than two decades of sustained USI. Methods: We selected 10- to 18-year-old subjects of both sexes (randomized cluster sampling) from all 9 provinces of Sri Lanka in this cross-sectional study. Blood, urine, and anthropometric data were collected and thyroid ultrasound scans were performed. Validated statistical methods were used to derive local population-specific reference ranges for all thyroid parameters. We also measured urine iodine concentration (UIC), salt, and water iodine concentrations. Results: Blood and urine samples from 2507 and 2473 subjects respectively, and ultrasound scans from 882 subjects were analyzed. Population-derived upper limits for thyroid peroxidase antibody (TPOAb) and TgAb, and reference ranges for triiodothyronine, thyroxine, and thyrotropin (total and age-year-related groups) were significantly different from manufacturer's reference ranges. Using these derived ranges, the prevalence of TPOAb was 10.3% and TgAb was 6.4%. Of the TPOAb-positive subjects, TPOAb were of low concentration in 66.2% (1-3 times the upper limit of the reference range [ULRR]) and showed the strongest association with subclinical hypothyroidism (SCH) at the highest concentrations (>4 ULRR). The prevalence of SCH was 3%. Median UIC (interquartile range) was 138.5 µg/L (79.4-219.0) with regional variability, and median thyroglobulin was 8.3 ng/mL (4.1-13.5). Goiter prevalence was 0.6% and 1.93% (thyroid volume compared to age and body surface area, respectively). Salt and water iodine concentrations were satisfactory. Conclusions: Sri Lanka has safely and effectively implemented USI with good sources of iodine, leading to sustained iodine sufficiency over more than two decades. The early postiodization TgAb surge (42.1%) has settled (6.4%), and despite a persistently high TPOAb prevalence (10.3%), SCH prevalence remains low (3%). Further studies should be undertaken to monitor thyroid autoimmune dysfunction in Sri Lankan children, using age-specific, population-derived reference ranges.

Barriers Against Prevention Programs for Iodine Deficiency Disorders in Europe: A Delphi Study.

Background: Although substantial progress has been made in recent decades in eliminating iodine deficiency, iodine deficiency disorders (IDDs) are still prevalent in European countries. Challenges include ineffective public health programs and discontinuation of IDD prevention. However, the barriers against the implementation and continuation of prevention and monitoring of IDD remain unclear. Therefore, the objective of our study was to identify potential barriers against pan-European IDD prevention and monitoring programs and to find solutions for the different challenges. Methods: We conducted a Delphi study consisting of three rounds. We identified potential participants with expertise and experience in relevant fields from all European countries, including policy makers, health care professionals, health scientists, and patient representatives. The Delphi method was conducted with open-ended questions and item ranking to achieve group consensus on potential barriers against national and pan-European IDD prevention and monitoring programs and related solutions to overcome those barriers. The answers of the Delphi rounds were analyzed using qualitative content analysis and descriptive analysis methods. In addition, we conducted two expert interviews to analyze and discuss the study results. Results: Eighty experts from 36 countries and different fields of work participated in the first Delphi round, 52 in the second, and 46 in the third. Potential barriers include challenges in the fields of knowledge and information, implementation and management, communication and cooperation, political support, and differences between the European countries. Ranked solutions addressing these barriers include cooperation with different stakeholders, gaining knowledge, sharing information, the development of a European program with national specification, European guidelines/recommendations, and European monitoring. The ranking gives a first overview as to which of these barriers would need to be solved most urgently and which solutions may be most helpful. Conclusion: In our study, we derived key information and first insights with regard to barriers against IDD prevention programs from a broad range of stakeholders. Most barriers were found in the category of implementation and management. Also a lack of political support seems to play an important role. The findings of our study may help decision makers in health policy to develop more effective IDD prevention and monitoring strategies.

Iodine status of pregnant women with obesity from inner city populations in the United Kingdom.

BACKGROUND/OBJECTIVES: Iodine is essential for foetal neurodevelopment and growth. Requirements increase in pregnancy to support increased thyroid hormone synthesis for maternal and foetal requirements, and for foetal transfer. Iodine deficiency in pregnancy is widely reported, and obesity has been associated with sub-optimal thyroid function. We evaluated iodine status and its relation with birthweight in a secondary analysis of pregnant women with obesity from multi-ethnic inner-city settings who participated in the UK Pregnancies Better Eating and Activity trial (UPBEAT). SUBJECTS/METHODS: Iodine and creatinine concentrations were evaluated in spot urine samples in the second (15+0-18+6 weeks, n = 954) trimester of pregnancy. We assessed iodine status as urinary iodine concentration (UIC) and urinary iodine-to-creatinine ratio (UI/Cr) and applied WHO/UNICEF/IGN population threshold of median UIC > 150 µg/L for iodine sufficiency. Relationships between iodine status and birthweight were determined using linear and logistic regression with appropriate adjustment, including for maternal BMI and gestational age. RESULTS: Median (IQR) UIC and UI/Cr in the second trimester of pregnancy were 147 µg/L (99-257) and 97 µg/g (59-165), respectively. An UI/Cr <150 µg/g was observed in 70% of women. Compared to women with UI/Cr >150 µg/g, there was a trend for women with UI/Cr <150 µg/g to deliver infants with a lower birthweight (ß = -60.0 g; 95% CI -120.9 to -1.01, P = 0.05). CONCLUSIONS: Iodine status of pregnant women with obesity from this cohort of UK women was suboptimal. Lower iodine status was associated with lower birthweight.

Iodine deficiency in Israeli pregnant women - a time for action.

Iodine is an essential micronutrient for thyroid gland function. Iodine deficiency disorders are a spectrum of conditions affecting the fetus, child, adolescent and adult. Iodine requirements are increased in pregnancy in order that the fetus receives enough maternal thyroxine via transplacental passage. Previous studies in Israel have shown widespread iodine deficiency by measurement of urinary iodine concentrations in school age children and adults. The present study clearly shows iodine deficiency in a group of 2nd trimester women as judged by measurement of serum thyroglobulin (a recently evaluated marker of iodine deficiency). An additional factor in this work is that the subjects all resided in an area using desalinated water. Desalination has previously been shown to significantly reduce the iodine content of water compared to water in Israel not subject to this process.The data in this group of pregnant women should serve as a wakeup call to the public health community to correct this deficiency which is known to significantly affect child neurodevelopment. There are several issues to be addressed. The knowledge base relating to iodine nutrition especially during pregnancy is low. An educational plan is required. The strategy for achieving adequate iodine nutrition in the population and particularly before and during pregnancy requires urgent review. While iodine supplementation before and during gestation can correct iodine deficiency, the provision of iodised salt in the community is recommended, similar to more than 80% of countries in the world.It is indeed a time for action to ensure the adequate intellectual performance of Israel's children.

Current controversies in the management of Graves' hyperthyroidism.

Introduction: The management of Graves' disease centers on the use of effective and well-established therapies, namely thionamide antithyroid drugs, radioactive iodine, and thyroidectomy. Optimal treatment strategies are however controversial and vary significantly across centers.Areas covered: This review addresses specific controversies in Graves' disease management including the choice of primary therapy, the approach to women planning pregnancy, and optimal strategies for antithyroid drug and radioiodine therapy.Expert opinion: Important considerations in choosing therapy include treatment efficacy, adverse effects, patient convenience, and resource settings. Recent data suggest that early and effective control of hyperthyroidism is key to improving cardiovascular morbidity and mortality. Studies addressing cancer risk in radioiodine-treated patients face methodological challenges and require clarification in appropriately designed studies. Remission rates with antithyroid drugs are comparable when thionamides are used alone (titration-regimen) or in combination with levothyroxine (block and replace) and can be optimized by extending treatment for at least 12-18 months. Fixed and calculated radioiodine activity regimens are both effective but entail a trade-off between convenience and precision in the administered activity. Optimal preconception strategies are still evolving but ablative treatment in advance of pregnancy offers the most pragmatic means of reducing adverse effects of hyperthyroidism in subsequent pregnancy.

Safety of antithyroid drugs in pregnancy: update and therapy implications.

Introduction: The thionamide antithyroid drugs, methimazole (MMI), its pro-drug derivative carbimazole (CMZ), and propylthiouracil (PTU) are the mainstay of treatment for hyperthyroidism in pregnancy. However, antithyroid drugs carry risks of adverse effects that can affect fetal and maternal well-being.Areas covered: This review provides an update on the safety of antithyroid drugs in pregnancy, focusing on the most serious concerns of severe liver disease and congenital anomalies.Expert opinion: PTU-induced liver disease is uncommon but can run a catastrophic course in pregnancy with a risk of liver failure and threats to maternal or fetal survival. Acute pancreatitis is a relatively rare occurrence that has been linked to thionamide use in a handful of reports in non-pregnant individuals. Observational studies on the risk of birth defects with antithyroid drug exposure in pregnancy overall show an increase in birth defect risk with exposure to CMZ/MMI, and to a lesser extent, PTU. Further studies are required to determine whether the currently recommended approach of switching between thionamide drugs in pregnancy improves outcomes. Ultimately, a preventative strategy of offering definitive therapy to hyperthyroid women of childbearing potential offers the best approach to truly reduce the risks of antithyroid drug adverse effects in pregnancy.

Indications for treatment of subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy.

Thyroid hormones are essential for maintaining a pregnancy and optimal fetal neurological development. Pregnancy places additional demands on the thyroid axis and around 5% of women who have their thyroid function checked during gestation will have borderline low thyroid function (subclinical hypothyroidism or isolated hypothyroxinemia) identified. These borderline low thyroid states are associated with adverse obstetric and offspring outcomes. Whilst it is well established that overt hypothyroidism requires treatment with levothyroxine, it is less clear whether there is any benefit of treating borderline low thyroid states. This review summarizes the potential indications for treatment of subclinical hypothyroidism and isolated hypothyroxinemia.

Stable Iodine Nutrition During Two Decades of Continuous Universal Salt Iodisation in Sri Lanka.

Universal salt iodisation (USI) was introduced in Sri Lanka in 1995. Since then, four national iodine surveys have assessed the iodine nutrition status of the population. We retrospectively reviewed median urine iodine concentration (mUIC) and goitre prevalence in 16,910 schoolchildren (6-12 years) in all nine provinces of Sri Lanka, the mUIC of pregnant women, drinking-water iodine level, and the percentage of households consuming adequately (15 mg/kg) iodised salt (household salt iodine, HHIS). The mUIC of schoolchildren increased from 145.3 µg/L (interquartile range (IQR) = 84.6-240.4) in 2000 to 232.5 µg/L (IQR = 159.3-315.8) in 2016, but stayed within recommended levels. Some regional variability in mUIC was observed (178.8 and 297.3 µg/L in 2016). There was positive association between mUIC in schoolchildren and water iodine concentration. Goitre prevalence to palpation was a significantly reduced from 18.6% to 2.1% (p < 0.05). In pregnant women, median UIC increased in each trimester (102.3 (61.7-147.1); 217.5 (115.6-313.0); 273.1 (228.9-337.6) µg/L (p = 0.000)). We conclude that the introduction and maintenance of a continuous and consistent USI programme has been a success in Sri Lanka. In order to sustain the programme, it is important to retain monitoring of iodine status while tracking salt-consumption patterns to adjust the recommended iodine content of edible salt.

Decision-Analytic Modeling Studies in Prevention and Treatment of Iodine Deficiency and Thyroid Disorders: A Systematic Overview.

Background: Prevention and treatment of iodine deficiency-related diseases remain an important public health challenge. Iodine deficiency can have severe health consequences, such as cretinism, goiter, or other thyroid disorders, and it has economic implications. Our aim was to give an overview of studies applying decision-analytic modeling to evaluate the effectiveness and/or cost-effectiveness of iodine deficiency-related prevention strategies or treatments related to thyroid disorders. Methods: We performed a systematic literature search in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica Database), Tuft's Cost-Effectiveness Analysis Registry, and National Health System Economic Evaluation Database (NHS EED) to identify studies published between 1985 and 2018 comparing different prevention or treatment strategies for iodine deficiency and thyroid disorders by applying a mathematical decision-analytic model. Studies were required to evaluate patient-relevant health outcomes (e.g., remaining life years, quality-adjusted life years [QALYs]). Results: Overall, we found 3950 studies. After removal of duplicates, abstract/title, and full-text screening, 17 studies were included. Eleven studies evaluated screening programs (mainly newborns and pregnant women), five studies focused on treatment approaches (Graves' disease, toxic thyroid adenoma), and one study was about primary prevention (consequences of iodine supplementation on offspring). Most of the studies were conducted within the U.S. health care context (n = 7). Seven studies were based on a Markov state-transition model, nine studies on a decision tree model, and in one study, an initial decision tree and a long-term Markov state-transition model were combined. The analytic time horizon ranged from 1 year to lifetime. QALYs were evaluated as health outcome measure in 15 of the included studies. In all studies, a cost-effectiveness analysis was performed. None of the models reported a formal model validation. In most cases, the authors of the modeling studies concluded that screening is potentially cost-effective or even cost-saving. The recommendations for treatment approaches were rather heterogeneous and depending on the specific research question, population, and setting. Conclusions: Overall, we predominantly identified decision-analytic modeling studies evaluating specific screening programs or treatment approaches; however, there was no model evaluating primary prevention programs on a population basis. Conclusions deriving from these studies, for example, that prevention is cost-saving, need to be carefully interpreted as they rely on many assumptions.

Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Behavior.

CONTEXT & OBJECTIVES: The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children's behavior. DESIGN & PARTICIPANTS: Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, "overtreated") and child neurodevelopment were reported. RESULTS: There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children. CONCLUSIONS: There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of "overtreated" mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment.