Suspected Spontaneous Reports of Birth Defects in the UK Associated with the Use of Carbimazole and Propylthiouracil in Pregnancy

The concept of a carbimazole embryopathy underlies current Endocrine Society advice to avoid this drug in early pregnancy, favouring propylthiouracil as an alternative for the treatment of maternal hyperthyroidism. We aimed to establish whether suspected spontaneous reporting of adverse drug reactions in the UK via the Yellow Card Scheme supports a carbimazole embryopathy and the lack of association between propylthiouracil and congenital anomalies. All birth defects related to maternal treatment with carbimazole or propylthiouracil reported over a 47-year period via the Yellow Card Scheme were analysed. 57 cases with 97 anomalies were reported following in utero exposure to carbimazole. These anomalies included aplasia cutis, choanal atresia, tracheo-oesophageal fistula, and patent vitellointestinal duct, which have previously been reported in association with carbimazole/methimazole exposure in utero. Only 6 cases with 11 anomalies were reported for propylthiouracil, all within the last 15 years. Therefore, these findings may support a carbimazole embryopathy. There are few birth defects associated with propylthiouracil, but this should be interpreted in the context of higher historical prescription rates for carbimazole

Treatment for primary hypothyroidism: current approaches and future possibilities

Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism

Thyroid research: stepping forward.

It is eight years since Thyroid Research was launched with an aim to enhance opportunities for scientists and clinicians, working in the rapidly advancing field of thyroidology, to publish their research (Thyroid Res 1(1):1, 2008). Right from the outset, Thyroid Research aspired to become a prominent journal in thyroidology with high quality publications. Over the years, the journal has not only survived in the increasingly competitive field of open-access academic journal publication, it has also been making a steady progress towards achieving this ambitious goal. Now, Thyroid Research is ready to step forward to begin a new chapter in its publication.This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.Published

Does Obesity Cause Thyroid Cancer? A Mendelian Randomization Study

Background: The incidence of thyroid cancer is rising, and relatively little is known about modifiable risk factors for the condition. Observational studies have suggested a link between adiposity and thyroid cancer; however, these are subject to confounding and reverse causality. Here, we used data from the UK Biobank and Mendelian randomization approaches to investigate whether adiposity causes benign nodular thyroid disease and differentiated thyroid cancer. Methods: We analyzed data from 379 708 unrelated participants of European ancestry in the UK Biobank and identified 1812 participants with benign nodular thyroid disease and 425 with differentiated thyroid carcinoma. We tested observational associations with measures of adiposity and type 2 diabetes mellitus. One and 2-sample Mendelian randomization approaches were used to investigate causal relationships. Results: Observationally, there were positive associations between higher body mass index (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08-1.22), higher waist-hip ratio (OR, 1.16; 95% CI, 1.09-1.23), and benign nodular thyroid disease, but not thyroid cancer. Mendelian randomization did not support a causal link for obesity with benign nodular thyroid disease or thyroid cancer, although it did provide some evidence that individuals in the highest quartile for genetic liability of type 2 diabetes had higher odds of thyroid cancer than those in the lowest quartile (OR, 1.45; CI, 1.11-1.90). Conclusions: Contrary to the findings of observational studies, our results do not confirm a causal role for obesity in benign nodular thyroid disease or thyroid cancer. They do, however, suggest a link between type 2 diabetes and thyroid cancer.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.WT_/Wellcome Trust/United Kingdompublished version, accepted version (12 month embargo), submitted versio

Preconception management of hyperthyroidism and thyroid status in subsequent pregnancy: a population-based cohort study

CONTEXT: Optimal thyroid status in pregnancy is essential in reducing the risk of adverse outcomes. The management of hyperthyroidism in women of reproductive age poses unique challenges and it is unclear how preconception treatment strategies impact on thyroid status in subsequent pregnancy. METHODS: We utilised the Clinical Practice Research Datalink (CPRD) database to evaluate all females aged 15-45 years, with a clinical diagnosis of hyperthyroidism and a subsequent pregnancy (January 2000 to December 2017). We compared thyroid status in pregnancy according to preconception treatment, namely, (1) antithyroid drugs up to or beyond pregnancy onset, (2) definitive treatment with thyroidectomy or radioiodine before pregnancy, and (3) no treatment at pregnancy onset. RESULTS: Our study cohort comprised 4712 pregnancies. TSH was measured in only 53.1% of pregnancies of which 28.1% showed suboptimal thyroid status (TSH >4.0 mU/L or TSH reference range). Pregnancies with prior definitive treatment were more likely to have suboptimal thyroid status compared to pregnancies starting during antithyroid drug treatment (OR = 4.72, 95%CI 3.50-6.36). A steady decline in the use of definitive treatment before pregnancy was observed from 2000-2017. A third (32.6%) of first trimester carbimazole-exposed pregnancies were switched to propylthiouracil while 6.0% of propylthiouracil-exposed pregnancies switched to carbimazole. CONCLUSION: The management of women with hyperthyroidism who become pregnant is suboptimal, particularly in those with preconception definitive treatment, and needs urgent improvement. Better thyroid monitoring and prenatal counselling are needed to optimise thyroid status, reduce teratogenic drug exposure, and ultimately reduce the risk of adverse pregnancy outcomes

Supplementary material for: "Preconception management of hyperthyroidism and thyroid status in subsequent pregnancy: a population-based cohort study"

Supplementary tables produced as part of a study of thyroid control in pregnancy among women with hyperthyroidism using CPRD data

Treatment and screening of hypothyroidism in pregnancy: results of a European survey

BackgroundMaternal hypothyroidism in pregnancy is associated with several adverse outcomes. The Endocrine Society Guidelines for the management of thyroid diseases in pregnancy were published in 2007; however, impact of the guidelines in routine clinical practice is unknown. Therefore, we have carried out a survey of members of the European Thyroid Association (ETA) to study current practices relating to the management of hypothyroidism in pregnancy.Subjects and methodsIn December 2010, we emailed an electronic questionnaire survey based on clinical case scenarios to 605 members of the ETA. Responses from 190 clinician members (from 28 European countries) were analyzed.ResultsFor a pregnant woman with newly diagnosed overt hypothyroidism, most responders initiated a full dose of l-thyroxine (l-T4). For a woman with hypothyroidism planning pregnancy, 50% recommended increasing the dose of l-T4 as soon as pregnancy is confirmed, whilst 43% favored testing thyroid function before adjusting the dose. Responders used diverse combinations of tests to monitor the dose of l-T4. The target of thyroid function tests that responders aimed to achieve with l-T4 was also inconsistent. Forty-two percent responders or their institutions screened all pregnant women for thyroid dysfunction, 43% performed targeted screening of only the high-risk group, whilst 17% did not carry out systemic screening. Timing of the screening, tests used, and criteria for starting treatment and monitoring were variable.ConclusionsThere is wide variation in the clinical practice relating to the treatment and screening of hypothyroidism during pregnancy in Europe

Effect of perchlorate and thiocyanate exposure on thyroid function of pregnant women from South-West England: a cohort study

This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site

A pilot randomised controlled trial of a preconsultation web-based intervention to improve the care quality and clinical outcomes of diabetes outpatients (DIAT)

notes: PMCID: PMC3731775This article was published in BMJ Open following peer review and can also be viewed on the journal’s website at http://bmjopen.bmj.com.Diabetes is a chronic condition associated with many long-term complications. People with diabetes need to actively manage their condition, which can be complex. In consultations with healthcare professionals, patients receive advice about their diabetes but do not always discuss things which concern them, perhaps because of the perceived limited time or embarrassment. We want to test a 'preconsultation' intervention in which the patient is supported by a healthcare assistant to complete a web-based intervention aimed at producing an agenda to help them identify important areas for discussion in the consultation. Use of this agenda may enable the patient to play a more active role in that consultation and consequently become more confident, and hence more successful, in managing their condition