Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

Objective: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society\u27s Journals Online web site at http://jcem.endojournals.org). Evidence: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. Conclusions: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented

Impact of Diabetes and Its Treatment on Cognitive Function Among Adolescents Who Participated in the Diabetes Control and Complications Trial

OBJECTIVE—The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13–19 years at entry in the Diabetes Control and Complications Trial (DCCT)

Neurocognitive function in children with compensated hypothyroidism: lack of short term effects on or off thyroxin

BACKGROUND: Although thyroxin therapy clearly is beneficial to children with frank hypothyroidism there is little data on the effects of thyroxin in children with compensated or subclinical hypothyroidism. The objective of this study was to determine the effect of thyroxin therapy on cognitive function in children with compensated hypothyroidism. The hypothesis was that thyroxin therapy would change neuropsychological function. METHODS: Eleven patients with a history of sub clinical hypothyroidism entered the study. At the start of the study, six out of the 11 were on thyroxin therapy, while 5 were off therapy. All patients underwent a battery of neuropsychological testing and thyroid function tests at the start of study. Based on the results of thyroid function tests, two of the 5 patients who were off thyroxin were started back on thyroxin. All of the 6 patients who were on thyroxin were taken off thyroxin. All patients then underwent repeat neuropsychological testing and thyroid functions after an average of 91 days. RESULTS: Thyroxin therapy could not be shown to have an effect on neuropsychological function in this short term study. Our patients had attention problems as compared to the normal population. No significant differences were found between our subjects and normal population standards in verbal processing, visual processing, motor speed/coordination and achievement. CONCLUSION: In this small, short term study, thyroxin therapy could not be shown to affect neuropsychological function in children with compensated hypothyroidism. These children may have attention problems but appear to have normal verbal and visual processing, motor speed/coordination and achievement

Expert consensus on neurodevelopmental outcomes in pregnancy pharmacovigilance studies

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes. Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders. Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use. Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance

The role of short-term memory and visuo-spatial skills in numerical magnitude processing: evidence from Turner syndrome

Peer reviewe

Discontinuation of thyroid hormone treatment among children in the United States with congenital hypothyroidism: findings from health insurance claims data

<p>Abstract</p> <p>Background</p> <p>Thyroid hormone treatment in children with congenital hypothyroidism can prevent intellectual disability. Guidelines recommend that children diagnosed with congenital hypothyroidism through newborn screening remain on treatment to at least 3 years of age, after which a trial off therapy can determine which children have transient hypothyroidism. The purpose of this study was to describe the rate at which children with congenital hypothyroidism in the United States discontinue thyroid hormone treatment in early childhood.</p> <p>Methods</p> <p>Retrospective analysis of the 2002-2006 MarketScan^®Commercial Claims and Encounters research databases and the 2001-2005 MarketScan Multi-State Medicaid databases. Children were classified as having congenital hypothyroidism based on billing codes and having filled a prescription for thyroid hormone treatment. Kaplan-Meier curve analysis was used to determine discontinuation rates.</p> <p>Results</p> <p>There were a total of 412 Medicaid-enrolled children and 292 privately-insured children with presumed congenital hypothyroidism included in this study. The overall birth prevalence of congenital hypothyroidism across both datasets was about 1 per 2,300. By 36 months, the percentage who had discontinued thyroid replacement treatment was 38% (95% Confidence Interval: 32%-44%). Medicaid-enrolled children had a more rapid decline in the first 24 months of treatment compared to those with private insurance (<it>P </it>= 0.02).</p> <p>Conclusions</p> <p>More than one-third of children treated for congenital hypothyroidism discontinued treatment within 36 months, which is inconsistent with current guidelines. It is not known how many of these children required continued treatment or experience adverse effects from discontinuation. These findings emphasize the critical need for follow-up systems to monitor the outcome of newborn screening.</p

Congenital hypothyroidism

Congenital hypothyroidism (CH) occurs in approximately 1:2,000 to 1:4,000 newborns. The clinical manifestations are often subtle or not present at birth. This likely is due to trans-placental passage of some maternal thyroid hormone, while many infants have some thyroid production of their own. Common symptoms include decreased activity and increased sleep, feeding difficulty, constipation, and prolonged jaundice. On examination, common signs include myxedematous facies, large fontanels, macroglossia, a distended abdomen with umbilical hernia, and hypotonia. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Thyroid dysgenesis accounts for 85% of permanent, primary CH, while inborn errors of thyroid hormone biosynthesis (dyshormonogeneses) account for 10-15% of cases. Secondary or central CH may occur with isolated TSH deficiency, but more commonly it is associated with congenital hypopitiutarism. Transient CH most commonly occurs in preterm infants born in areas of endemic iodine deficiency. In countries with newborn screening programs in place, infants with CH are diagnosed after detection by screening tests. The diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level. Other diagnostic tests, such as thyroid radionuclide uptake and scan, thyroid sonography, or serum thyroglobulin determination may help pinpoint the underlying etiology, although treatment may be started without these tests. Levothyroxine is the treatment of choice; the recommended starting dose is 10 to 15 mcg/kg/day. The immediate goals of treatment are to rapidly raise the serum T4 above 130 nmol/L (10 ug/dL) and normalize serum TSH levels. Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome. Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life and every 3-4 months thereafter. In general, the prognosis of infants detected by screening and started on treatment early is excellent, with IQs similar to sibling or classmate controls. Studies show that a lower neurocognitive outcome may occur in those infants started at a later age (> 30 days of age), on lower l-thyroxine doses than currently recommended, and in those infants with more severe hypothyroidism

Adult reversal of cognitive phenotypes in neurodevelopmental disorders

Recent findings in mice suggest that it is possible to reverse certain neurodevelopmental disorders in adults. Changes in development, previously thought to be irreparable in adults, were believed to underlie the neurological and psychiatric phenotypes of a range of common mental health problems with a clear developmental component. As a consequence, most researchers have focused their efforts on understanding the molecular and cellular processes that alter development with the hope that early intervention could prevent the emergent pathology. Unexpectedly, several different animal model studies published recently, including animal models of autism, suggest that it may be possible to reverse neurodevelopmental disorders in adults: Addressing the underlying molecular and cellular deficits in adults could in several cases dramatically improve the neurocognitive phenotypes in these animal models. The findings reviewed here provide hope to millions of individuals afflicted with a wide range of neurodevelopmental disorders, including autism, since they suggest that it may be possible to treat or even cure them in adults