Search

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.

Thyroid hormones have long been known to have a range of effects on the cardiovascular system. However, significant knowledge gaps exist concerning the precise molecular and biochemical mechanisms governing these effects and the optimal strategies for management of abnormalities in thyroid function in patients with and without preexisting cardiovascular disease. In September 2017, The National Heart, Lung, and Blood Institute convened a Working Group with the goal of developing priorities for future scientific research relating thyroid dysfunction to the progression of cardiovascular disease. The Working Group reviewed and discussed the roles of normal thyroid physiology, the consequences of thyroid dysfunction, and the effects of therapy in three cardiovascular areas: cardiac electrophysiology and arrhythmias, the vasculature and atherosclerosis, and the myocardium and heart failure. This report describes the current state of the field, outlines barriers and challenges to progress, and proposes research opportunities to advance the field, including strategies for leveraging novel approaches using omics and big data. The Working Group recommended research in three broad areas: 1) investigation into the fundamental biology relating thyroid dysfunction to the development of cardiovascular disease and into the identification of novel biomarkers of thyroid hormone action in cardiovascular tissues; 2) studies that define subgroups of patients with thyroid dysfunction amenable to specific preventive strategies and interventional therapies related to cardiovascular disease; and 3) clinical trials focused on improvement in cardiovascular performance and cardiovascular outcomes through treatment with thyroid hormone or thyromimetic drugs.

Background: Programs initiated to prevent iodine deficiency disorders (IDD) may not remain effective due to changes in government policies, commercial factors, and human behavior that may affect the efficacy of IDD prevention programs in unpredictable directions. Monitoring and outcome studies are needed to optimize the effectiveness of IDD prevention., Summary: Although the need for monitoring is compelling, the current reality in Europe is less than optimal. Regular and systematic monitoring surveys have only been established in a few countries, and comparability across the studies is hampered by the lack of centralized standardization procedures. In addition, data on outcomes and the cost of achieving them are needed in order to provide evidence of the beneficial effects of IDD prevention in countries with mild iodine deficiency., Conclusion: Monitoring studies can be optimized by including centralized standardization procedures that improve the comparison between studies. No study of iodine consumption can replace the direct measurement of health outcomes and the evaluation of the costs and benefits of the program. It is particularly important that health economic evaluation should be conducted in mildly iodine-deficient areas and that it should include populations from regions with different environmental, ethnic, and cultural backgrounds.

Background: As defined by the Dietary Supplement Health and Education Act 1997, such substances as herbs and dietary supplements fall under general Food and Drug Administration supervision but have not been closely regulated to date. We examined the thyroid hormone content in readily available dietary health supplements marketed for "thyroid support.", Methods: Ten commercially available thyroid dietary supplements were purchased. Thyroid supplements were dissolved in 10 mL of acetonitrile and water with 0.1% trifloroacetic acid and analyzed using high-performance liquid chromatography for the presence of both thyroxine (T4) and triiodothyronine (T3) using levothyroxine and liothyronine as a positive controls and standards., Results: The amount of T4 and T3 was measured separately for each supplement sample. Nine out of 10 supplements revealed a detectable amount of T3 (1.3-25.4 μg/tablet) and 5 of 10 contained T4 (5.77-22.9 μg/tablet). Taken at the recommended dose, 5 supplements delivered T3 quantities of greater than 10 μg/day, and 4 delivered T4 quantities ranging from 8.57 to 91.6 μg/day., Conclusions: The majority of dietary thyroid supplements studied contained clinically relevant amounts of T4 and T3, some of which exceeded common treatment doses for hypothyroidism. These amounts of thyroid hormone, found in easily accessible dietary supplements, potentially expose patients to the risk of alterations in thyroid levels even to the point of developing iatrogenic thyrotoxicosis. The current study results emphasize the importance of patient and provider education regarding the use of dietary supplements and highlight the need for greater regulation of these products, which hold potential danger to public health.

Background: Dietary iodine intake is required for the production of thyroid hormone. Consequences of iodine deficiency include goiter, intellectual impairments, growth retardation, neonatal hypothyroidism, and increased pregnancy loss and infant mortality., Summary: In 1990, the United Nations World Summit for Children established the goal of eliminating iodine deficiency worldwide. Considerable progress has since been achieved, largely through programs of universal salt iodization. Approximately 70% of all households worldwide currently have access to adequately iodized salt. In 2013, as defined by a national or subnational median urinary iodine concentration of 100-299 μg/L in school-aged children, 111 countries have sufficient iodine intake. Thirty countries remain iodine-deficient; 9 are moderately deficient, 21 are mildly deficient, and none are currently considered severely iodine-deficient. Ten countries have excessive iodine intake. In North America, both the United States and Canada are generally iodine-sufficient, although recent data suggest pregnant U.S. women are mildly iodine-deficient. Emerging issues include discrepancies between urinary iodine status in pregnant women compared to school-aged children in some populations, the problem of re-emerging iodine deficiency in parts of the developed world, the importance of food industry use of iodized salt, regions of iodine excess, and the potential effects of initiatives to lower population sodium consumption on iodine intake., Conclusions: Although substantial progress has been made over the last several decades, iodine deficiency remains a significant health problem worldwide and affects both industrialized and developing nations. The ongoing monitoring of population iodine status remains crucially important, and particular attention may need to be paid to monitoring the status of vulnerable populations, such as pregnant women and infants. There is also need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition. Finally, it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines.

Background: Environmental exposures, ranging from perchlorate in rocket fuel to polychlorinated biphenols, have been shown to influence thyroid function. Although most of these agents are associated with reduced thyroid hormone levels or impaired thyroid hormone action, a number of environmental exposures confer an increased risk of autoimmune thyroid disease., Summary: Factors that increase autoimmune thyroid disease risk include radiation exposure, both from nuclear fallout and medical radiation, increased iodine intake, as well as several contaminants in the environment that influence the thyroid. Although approximately 70% of the risk for developing autoimmune thyroid disease is attributable to genetic background, environmental triggers are thought to play a role in the development of autoimmune thyroid disease in susceptible individuals., Conclusions: Understanding the association of environmental agents with thyroid dysfunction can be utilized to reduce the risk to populations. Knowledge of the specific factors that trigger autoimmune thyroid disease and their mode of action, however, may also inform risk reduction in the individual patient. These factors are especially relevant for those at increased risk of autoimmune thyroid disease based on family history.

Objective: It has been difficult to determine the sources of U.S. dietary iodine. This study was designed to validate a self-administered questionnaire about dietary iodine sources., Design: We constructed a questionnaire to assess iodine intake in 46 healthy Boston-area adult volunteers. Questionnaire information was correlated with subjects' 24-hour food diaries. Spot morning urine cotinine (a metabolite of nicotine from cigarette smoking) and iodine concentrations were measured., Main Outcomes: 91% of 46 subjects were women [mean (+/- SD) age of 38 (+/- 10) years]. Information from 24-hour food diaries correlated well with questionnaire data. The median urinary iodine concentration (UIC) was 140 microg/L (range: 18-845 microg/L). There were significant positive associations between intake of yogurt (n = 9, p = 0.01) and saltwater fish (n = 6, p = 0.0003), and an inverse correlation between bagels (n = 5, p = 0.0006) and UIC. We found no associations between self-reported milk, iodized salt, tobacco use, or urinary cotinine and UIC., Conclusion: The questionnaire may not have been sufficiently comprehensive. Given the importance of adequate dietary iodine intake, particularly among women of childbearing age, further studies are warranted to determine important sources of dietary iodine in the United States.

Mild maternal hypothyroidism during pregnancy can adversely affect infant development. We studied thyrotropin (TSH) levels in mothers of premature and low-birth-weight infants in Colombia, where iodized salt supplements the diet to correct iodine deficiency. The additional impact of salt restriction in mothers with hypertensive disorders was examined. Blood was spotted on filter paper from 404 mothers and their infants. Using radioimmunoassay (RIA), TSH was measured in the mothers, and TSH and thyroxine in their infants at three postpartum times. Initially, mothers had high TSH levels (i.e., TSH > 10 mU/L in half the mothers at the first assessment). Fourteen days later, only 9.3%, and at calculated term 7.5% were greater than 10 mU/L. Maternal TSH levels correlated with infant birth weight and gestational age (r = 0.47, and r = 0.49, p < 0.01). Initial TSH values were higher in salt restricted (20.1 +/- 2 mU/L, n = 76) versus control mothers (14.6 +/- 0.85, n = 328, p < 0.01), dropping dramatically in both groups 14 days later (to 3.4 +/- 0.7 mU/L vs. 2.8 +/- 0.4 mU/L) and at calculated term (2.8 +/- 0.4 mU/L vs. 2.3 +/- 0.6 mU/L). Increased maternal TSH levels during pregnancy in an iodine-deficient area may be aggravated by salt restriction. Monitoring TSH and supplementing iodine or thyroxine are recommended in pregnancy, especially if dietary salt restriction is prescribed.

Monitoring and evaluation are the last phases of a national iodine deficiency disorders (IDD) control program but among the most important. This paper summarizes the latest recommendations by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the International Council for Control of Iodine Deficiency Disorders (ICCIDD) about indicators and their normative values for monitoring the progress of IDD elimination and illustrates the successful monitoring programs in Switzerland and in China. Salt is the usual vehicle for iodine supplementation and quality control for iodine content can be assessed quantitatively by titration and qualitatively by simple test kits that can be used in the field. The most useful indicator of iodine nutrition is the median urinary iodine concentration. Thyroid size, especially by ultrasound, and neonatal thyrotropin (TSH) are also valuable. In Switzerland, access to iodized salt on a voluntary basis started in 1922. The initial level of iodization, 1.9-3.75 ppm iodine as potassium iodide (KI), was slowly increased to 15 ppm, and recently to 20 ppm, after careful epidemiologic and biologic monitoring. Elimination of IDD has been highly successful. The program costs US dollars 0.07 per year per person. In China, a national program of iodized salt (10-30 ppm) started in 1960 under the authority of the central government and rapidly expanded. National monitoring surveys have taken place every 2 years since 1993. Median urinary iodine, initially low, increased to 165 microg/L in 1995 and to 306 microg/L in 1999, prompting a decrease in the amount of iodine added to salt. The total goiter rate decreased to 20.4% in 1995 and to 8.8% in 1999. IDD can presently be considered as eliminated in China. Review of monitoring in the 128 other major countries affected by IDD shows extremely variable achievements, with evidence of IDD elimination in at least 18 additional countries. Some countries that were severely iodine deficient in the past are now exposed to iodine excess and risk its effects. Sustainable elimination of IDD is within reach and would constitute an unprecedented global success story in the field of noncommunicable diseases, but continuing vigorous action is required to attain this goal.

In the realm of preventive medicine, there are three distinct types of prevention that can be defined. Primary prevention is the prevention of new disease in previously healthy individuals, usually achieved by decreasing risk factors for disease. Secondary prevention is the prevention of progression of mild or latent disease to more severe disease, and typically involves screening for occult disease. Tertiary prevention is the term used by some to describe medical care intended to improve already established disease. The role of primary prevention of thyroid disease in the United States is uncertain, because iodine deficiency is not clearly known to be a problem. In the case of secondary prevention of thyroid disease, this would necessarily involve screening of individuals for subclinical hyperthyroidism or hypothyroidism with thyrotropin (TSH) testing. Using data from a large prevalence study and from the 2000 U.S. Census, it can be calculated that approximately 15 million adults have unrecognized thyroid disease, mostly subclinical hypothyroidism. If detected, secondary prevention might also entail treatment with antithyroid drugs/radioiodine or thyroxine to prevent sequelae or progression to a more advanced degree of thyrotoxicosis or thyroid failure, respectively. Over the next 20 years, it can be calculated that approximately 5 million people, mostly with subclinical hypothyroidism, will progress to overt disease. Tertiary prevention of thyroid disease would involve avoiding iatrogenic disease, such as thyroid hormone overdose. From epidemiologic data it can be calculated that approximately 600,00 elderly individuals have iatrogenic hyperthyroidism from thyroid hormone overdose, putting them at risk for atrial fibrillation and osteoporosis. Together, these data suggest that the notion of preventive medicine in the United States should be expanded to include thyroid disease as a target for secondary and tertiary intervention.

Pregnancy has variable effects on thyroid hormone concentrations throughout pregnancy as well as being associated with goiter. The latter is largely preventable by ensuring optimal iodine intake of at least 200 microg/d. Immunologic changes in pregnancy include a so-called T(H)2 shift that reverts to T(H)1 status around birth or early in the postpartum period. Hyperthyroidism during gestation, usually caused by Graves' disease, is rare (0.2%) and is best managed medically with propylthiouracil; thyroid-stimulating antibodies should be measured. Prevention of the deleterious effects of Graves' disease includes adequate preconception advice, adequate monitoring during pregnancy, and total avoidance of (131)I therapy during pregnancy. Hypothyroidism during pregnancy has an incidence of 2.5% although there is a 10% incidence of thyroid peroxidase (TPO)-antibody positivity in early gestation. There are convincing epidemiologic data to show that suboptimal thyroid function in pregnancy is associated with impaired neurointellectual development (e.g., 19% with IQ < 85 compared to 5% in one study). Therefore, there is a case for screening for thyroid function in early pregnancy with thyroxine (T(4)) intervention therapy. Maintenance of optimal iodine intake is critical to prevent nonautoimmune gestational maternal hypothyroxinaemia. Postpartum thyroid dysfunction (PPTD) occurs in 5%-9% of women and in up to 50% of TPO-antibody positive women (as ascertained in early pregnancy). Prevention of PPTD at this time could only be achieved by pregestational ablation of the thyroid. Another approach is to at least improve the prediction of postpartum thyroid disease (PPT) because the TPO antibody has a sensitivity of only 50%.