Creswell J. Eastman

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 Societys 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.

ENDEMIC GOITRE IN CENTRAL CHINA CAUSED BY EXCESSIVE IODINE INTAKE

Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 micrograms/l. Goitres were present in 65% (n = 120) and 15.4% (n = 51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of overt hypothyroidism were detected in the high-iodine village.Thyroid status was examined in children from two villages in central China where the iodine concentrations in drinking water were 462.5 and 54 µg/1. Goitres were present in 65% (n = 120) and 15.4% (n=51), respectively. All children in both groups were clinically euthyroid and neurologically normal. Growth measurements and intellectual performance were similar in the two groups. Children from the high-iodine village had a lower mean serum triiodothyronine and higher serum free thyroxine and serum thyroid-stimulating hormone concentrations than the children from the control village. 2 cases of

The changing epidemiology of iodine deficiency

Globally, about 2 thousand million people are affected by iodine deficiency. Although endemic goitre is the most visible sign of iodine deficiency, its most devastating consequence is brain damage causing mental retardation in children. The relationship between iodine deficiency and brain damage was not clearly established until the 1980s when the term iodine deficiency disorders (IDDs), which encompass a spectrum of conditions caused by iodine deficiency, was introduced. This paradigm shift in the understanding of the clinical consequences of iodine deficiency led to a change in iodine deficiency assessment. The median urinary iodine excretion level has been recommended as the preferred indicator for monitoring population iodine deficiency status since 2001. The 2007 WHO urinary iodine data in schoolchildren from 130 countries revealed that iodine intake is still insufficient in 47 countries. Furthermore, about one-third of countries lack national estimates of the prevalence of iodine deficiency. The picture that has emerged from available data worldwide over the past two decades is that IDDs are not confined to remote, mountainous areas in developing countries, but are a global public health problem that affects most countries, including developed countries and island nations. The recognition of the universality of iodine deficiency highlights the need to develop and apply new strategies to establish and maintain sustainable IDD elimination and strengthen regular monitoring programmes.

Prevalence of thyroid disease in an older Australian population

Aim: To determine the prevalence of thyroid disease in an older Australian population in a population‐based cross‐sectional study.

THYROID AUTOIMMUNITY IN ENDEMIC GOITRE CAUSED BY EXCESSIVE IODINE INTAKE

The pathophysiology of endemic goitre caused by excessive iodine intake is not well defined. By interacting with the immune system, iodine excess may trigger the development of autoimmune thyroid disease such as lymphocytic Hashimotos thyroiditis (LT). In an attempt to examine this further, we compared the presence of thyroid autoantibodies in 29 goitrous children, from an iodine excess area, and in 26 healthy children, from an iodine sufficient area, of north central China. Serum was tested for antimicrosomal (MAb), anti‐thyroglobulin (TgAb), second colloid antigen antibodies (CA2‐Ab) and TSH binding inhibitory immunoglobulins (TBII). Affinity chromatographically purified IgG was tested for thyroid growth‐stimulating activity (TGI) by two different methods: a sensitive cytochemical bioassay (CBA) using guinea‐pig thyroid explants and a mitotic arrest assay (MAA) employing a continuous rat thyroid cell line (FRTL‐5). We found no increased prevalence of LT in patients with endemic iodine goitre. The levels of MAb, TgAb and CA2‐Ab did not differ significantly between the two groups of children. Further, TBII were not present in either group. Thyroid growth‐stimulating immunoglobulins (TGI) were the major autoantibodies found in children with goitres caused by iodine excess. In the CBA, 12 of 20 (60%) goitrous children and 0 of 12 (0% P<0.05) healthy children were positive for TGI. Similar results were found in the MAA, and a good correlation between results of the CBA and MAA was found (P = 0.003). Maximal TGI activity in dose‐response CBA showed a good relation with clinical goitre size (r = 0.63; P < 0.05) indicating a possible pathophysiological role for these antibodies. We conclude that endemic iodine goitre is not associated with Hashimotos lymphocytic thyroiditis. Nevertheless, autoimmune growth factors such as TGI may play a primary role in the pathogenesis of thyroid growth in this condition.

Iodine Induced Lymphocytic Thyroiditis in the Bb/W Rat: Early and Late Immune Phenomena

The effect of iodine excess on thyroid function and on the immunological sequence of events leading to lymphocytic thyroiditis (LT) was studied in the NB subline of BB/W rats to determine the mechanisms by which the level of iodine intake influences the development of LT in this animal model. Iodine supplemented water (500 micrograms/l, Group 1 or 500 mg/l, Group 2) or non-iodine supplemented tap water (Group 3) was given to breeding pairs and their offspring ad libitum. A Wistar rat group, also given tap water (Group 4) served as controls. To determine the immunological sequence of events, the phenotypic nature of the infiltrating thyroid lymphocytes was examined by specific immunoperoxidase staining in BB/W and Wistar rats at 6, 9, 12, and 15 weeks. Antigen-presenting cells and class II (Ia) antigen expression on thyrocytes were also examined. The first immunological event apparent in the iodine-treated BB/W rats was a sharp increase in the number of Ia positive dendritic cells at 9 weeks compared with control BB/W and Wistar rats. In the iodine excess groups dendritic cells were associated with scattered areas of lymphocytic infiltration, comprising predominantly T helper cells (W3/25). T suppressor cells (OX 8) and IL-2 receptor positive activated T-cells (OX 39) were both present in small numbers. B-cells (OX 12) were absent. In addition, thyrocytes did not exhibit Ia antigen expression. By contrast, lymphocytic infiltration was not found at 9 weeks in control BB/W rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal TSH screening: is it a sensitive and reliable tool for monitoring iodine status in populations?

Iodine deficiency is the most common cause of preventable brain damage in the newborn. The indicators for assessing iodine nutritional status include urinary iodine excretion, thyroid size, thyroid stimulating hormone (TSH) and thyroglobulin (Tg) concentrations in the blood. Neonatal TSH concentration is increased when the supply of thyroid hormone and iodine from the maternal circulation to the foetus has been compromised. The World Health Organization (WHO) has suggested that when a sensitive assay is used on samples collected 3-4 days after birth, a <3% frequency of TSH concentrations >5 mIUl(-1) indicates iodine sufficiency in a population. However, many studies have attempted to apply the frequency of neonatal TSH values >5 mIUl(-1) in determining population iodine status and monitoring intervention programmes, and although some have proven to be successful, most have provided conflicting or uncertain data. This is due to the many technical issues that remain unresolved on the use of neonatal TSH screening for monitoring iodine status, making it doubtful as a sensitive and reliable quantitative tool. More research is required to resolve these issues. In the interim, WHO should consider withdrawing its current guidelines for neonatal TSH screening for monitoring iodine deficiency in populations.

Five-year incidence and progression of thyroid dysfunction in an older population

Background: Very few studies have assessed both the incidence and progression of thyroid dysfunction in a single older population‐based cohort. In this study, we aimed to assess the 5‐year incidence, progression and risk factors for development of thyroid dysfunction in an older Australian population.

Screening for thyroid disease and iodine deficiency

The high global prevalence of iodine deficiency and autoimmune thyroid disorders and the mental and physical consequences of these disorders creates a huge human and economic burden that can be prevented, in large part, by early detection and appropriate preventative or therapeutic measures. The availability of sophisticated, sensitive and accurate laboratory testing procedures provides an efficient and effective platform for the application of screening for these disorders. Measurement of urine iodine concentration (UIC) in school children or pregnant women is the recommended indicator for screening populations for iodine deficiency. The severity of the iodine deficiency is classified according to the UIC. Measurement of serum thyrotropin (TSH) as an indicator for population iodine deficiency is used only in neonates and is supplementary to UIC screening. Other indicators such as goitre rates, thyroid function and serum thyroglobulin levels are useful adjunctive but not frontline process indicators. The human and economic benefits of screening for congenital hypothyroidism by measurement of heel-prick TSH have been well documented and justify its universal application. Using this measurement for monitoring population iodine intake is recommended by the World Health Organization but further validation is required before it can be universally recommended. Subclinical thyroid dysfunction is readily detected by current highly sensitive serum TSH assays and its prevalence appears to increase with age, varies with iodine intake and ethnicity and may occur in up to 20% of older age people. Subclinical hyperthyroidism is the less common disorder and screening cannot be justified because of its low prevalence and minimal or insignificant clinical effects. The argument for screening for subclinical hypothyroidism in middle-aged and older women is stronger but lacks evidence of benefit from randomised controlled trials or cost benefit analyses of therapeutic intervention, so it cannot currently be recommended. The publication of recent Clinical Practice Guidelines for management of thyroid disease in pregnancy from the American Endocrine Society and American Thyroid Association provide persuasive arguments for early detection and treatment of overt and subclinical hypothyroidism to prevent obstetric complications and potential neurocognitive disorders in the offspring. Given the indisputable benefits of therapy, the sooner thyroid dysfunction is detected, before or as early as possible in gestation, the more likely there will be a better outcome. Because of the limitations of targeted case detection in women at risk of subclinical hypothyroidism, there has been a gradual shift in opinion to universal TSH screening of all women as soon as practicable in pregnancy. While a positive association exists between the presence of anti-thyroid antibodies and increased pregnancy loss, universal screening of all pregnant women for underlying autoimmune thyroid disease is difficult to justify until there is evidence of beneficial outcomes from randomised controlled trials. Vigorous and liberal targeted case detection remains the recommended strategy to address this problem.

Iodine Intake and Thyroid Function in Pregnant Women in a Private Clinical Practice in Northwestern Sydney before Mandatory Fortification of Bread with Iodised Salt

Aim. The primary objective of the study was to assess the iodine nutritional status, and its effect on thyroid function, of pregnant women in a private obstetrical practice in Sydney. Methods. It was a cross-sectional study undertaken between November 2007 and March 2009. Blood samples were taken from 367 women at their first antenatal visit between 7 and 11 weeks gestation for measurement of thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels and spot urine samples for urinary iodine excretion were taken at the same time as blood collection. Results. The median urinary iodine concentration (UIC) for all women was 81 μg/l (interquartile range 41–169 μg/l). 71.9% of the women exhibited a UIC of <150 μg/l. 26% of the women had a UIC <50 μg/l, and 12% had a UIC <20 μg/l. The only detectable influences on UIC were daily milk intake and pregnancy supplements. There was no statistically significant association between UIC and thyroid function and no evidence for an effect of iodine intake on thyroid function. Conclusions. There is a high prevalence of mild to moderate iodine deficiency in women in Western Sydney but no evidence for a significant adverse effect on thyroid function. The 6.5% prevalence of subclinical hypothyroidism is unlikely to be due to iodine deficiency.