Basics of prevention and management of iodine-based contrast media-induced thyroid dysfunction - position paper by the Polish Society of Endocrinology.

Medical practice involves a high number of radiological examinations using iodinated contrast media (ICM). Therefore, it is crucial for doctors of different specialties to be aware of possible adverse effects associated with ICM use. The most common and well characterized adverse effect is contrast-induced nephropathy, whereas thyroidal adverse reactions remain a diagnostic and therapeutic dilemma. ICM-induced thyroid dysfunction represents a highly heterogenous group of thyroid disorders. Due to supraphysiological iodine concentration, ICM can induce both hyper- and hypothyroidism. In most cases, the ICM-induced thyroid dysfunction is oligo- or asymptomatic, mild, and transient. In rare cases, however, the ICM-induced thyroid dysfunction may be severe and life threatening. Recently, the European Thyroid Association (ETA) Guidelines for the Management of Iodine-Based Contrast Media-Induced Thyroid Dysfunction were published. The authors advise an individualized approach to prevention and treatment of ICM-induced thyroid dysfunction, based on patient's age, clinical symptoms, pre-existing thyroid diseases, coexisting morbidities, and iodine intake. There is a geographic variation of ICM-induced thyroid dysfunction prevalence, which is linked to iodine intake. The prevalence of ICM-induced hyperthyroidism, which may pose a serious therapeutic challenge, is greater in countries with iodine deficiency. Poland is a region with a history of iodine deficiency, contributing to an increased prevalence of nodular thyroid disease, especially in the elderly. Therefore, the Polish Society of Endocrinology has proposed national, simplified principles of ICM-induced thyroid dysfunction prevention and treatment.

[Elimination of iodine deficiency is a concern for the health of the nation. An excursion into the history, scientific aspects and the current state of the legal regulation of the problem in Russia].

The article presents current data on the prevalence of thyroid diseases associated with iodine deficiency in Russia, focuses on the features of the comorbidity of iodine deficiency and autoimmune thyroid pathologies, methods for assessing the iodine supply of the population. Information about the study and prevention of iodine deficiency diseases (IDD) in the USSR and the Russian Federation is given. The history of legislative initiatives aimed at eliminating dietary iodine deficiency and preventing IDD is illustrated in detail. The ways of solving the problem of iodine deficiency at the present stage, both at the federal and regional levels, are proposed.

Thyroid, Diet, and Alternative Approaches.

BACKGROUND: Increasingly, patients are asking their physicians about the benefits of dietary and alternative approaches to manage their diseases, including thyroid disease. We seek to review the evidence behind several of the vitamins, minerals, complementary medicines, and elimination diets that patients are most commonly using for the treatment of thyroid disorders. SUMMARY: Several trace elements are essential to normal thyroid function, and their supplementation has been studied in various capacities. Iodine supplementation has been implemented on national scales through universal salt iodization with great success in preventing severe thyroid disease, but can conversely cause thyroid disorders when given in excess. Selenium and zinc supplementation has been found to be beneficial in specific populations with otherwise limited generalizability. Other minerals, such as vitamin B12, low-dose naltrexone, and ashwagandha root extract, have little to no evidence of any impact on thyroid disorders. Avoidance of gluten and dairy has positive impacts only in patients with concomitant sensitivities to those substances, likely by improving absorption of levothyroxine. Avoidance of cruciferous vegetables and soy has little proven benefit in patients with thyroid disorders. CONCLUSION: While many patients are seeking to avoid conventional therapy and instead turn to alternative and dietary approaches to thyroid disease management, many of the most popular approaches have no proven benefit or have not been well studied. It is our responsibility to educate our patients about the evidence for or against benefit, potential harms, or dearth of knowledge behind these strategies.

[Prevention of iodine deficiency diseases: focus on regional targeted programs].

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than the established norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

Role of Dietary Supplements in Thyroid Diseases.

BACKGROUND: Thyroid hormones play a vital role in regulating our body's metabolism. Two important thyroid hormones released from the thyroid gland are tri-iodothyronine (T3) and tetra-iodothyronine (T4). Thyroid-stimulating hormone and thyroid regulating hormone control the T3 and T4 levels in our body. Increased TSH levels indicate hypothyroidism and decreased TSH levels indicate hyperthyroidism. Iodine is a crucial nutrient for the synthesis of thyroid hormones and is mostly obtained from our diet. Other essential nutrients for the thyroid hormones formation include selenium, iron, vitamin D, vitamin B12, etc. Dietary changes in these nutrients can result in alterations in thyroid function and structure. Although normally, the hormonal diseases cannot be cured, but we can improve their signs and symptoms using suitable dietary supplements. OBJECTIVE: The aim of the study was to thoroughly analyze the various benefits and risks associated with the use of dietary supplements for the prevention and treatment of various thyroid disorders, like hypothyroidism, as seen in Hashimoto's thyroiditis; hyperthyroidism, as seen in Graves' disease; sick euthyroidism and subclinical hypothyroidism. METHODS: Literature was searched using the search terms "dietary supplements+thyroid diseases" on Pubmed, Google Scholar, Scopus, Cochrane Library, and other search engines, and data were collected from 1967 to November, 2021, including research inputs from the authors. The literature was thoroughly searched, and deep knowledge was acquired on this topic, which was then sequentially organized and summarized using suitable tables and figures. CONCLUSION: After analyzing various studies on this topic, we arrived at the conclusion that although there are various claimed and observed health benefits of dietary supplements in the prevention and treatment of various thyroid disorders, still several studies have shown too many risks to be associated with the use of dietary supplements, and people using these products should be aware of these risks in order to use them very judiciously for the improvement of their thyroid status.

Risk perception regarding implementation of iodine thyroid blocking during a nuclear disaster of mothers living near a nuclear power station in Japan.

Pre-emptive evacuation orders following the accident at the Fukushima Daiichi Nuclear Power Station (FDNPS) in March 2011 and subsequent regulatory limits regarding contaminated food, milk, and water minimized the external and internal radiation exposure doses of nearby residents. However, with regard to implementation of iodine thyroid blocking (ITB), residents were confused because no information on the matter was released by the central and/or local governments. Based on lessons learned from the FDNPS accident, many countries have revised their guidelines regarding ITB during nuclear disasters. To adequately revise such guidelines and ensure effective ITB implementation during a nuclear disaster, however, residents' perceptions of ITB must be clarified. In this study, the perception of risks associated with ITB was investigated in mothers residing near the Sendai Nuclear Power Plant (SNPP) in Kagoshima Prefecture, Japan. Of the 520 mothers surveyed, 467 (89.8%) expressed anxiety regarding the administration of potassium iodine (KI) to their children. Logistic regression analysis revealed that the mothers' anxiety regarding the administration of KI to their children was positively correlated with their wish to consult an expert about KI and their hesitation to let their children eat foods produced in Fukushima, and negatively correlated with having confidence about administering KI to their children. Careful communication of potential risks to mothers residing near nuclear power plants is thus critical for implementing effective ITB in children.

No significant association between stable iodine intake and thyroid dysfunction in children after the Fukushima Nuclear Disaster: an observational study.

PURPOSE: Stable iodine prophylaxis helps prevent childhood thyroid cancer in nuclear emergencies; however, there is limited information on its effect on thyroid function. This study aimed to examine thyroid function and autoimmunity among children and adolescents that took stable iodine after the Fukushima Nuclear Disaster. METHODS: For this observational study, data were obtained from children and adolescents that underwent thyroid cancer screening at Hirata Central Hospital from April 2012 to March 2018. Participant characteristics, including possible hypothyroidism and hyperthyroidism, were compared between the prophylaxis and no-prophylaxis groups. Multivariable logistic regression models were used to assess for possible hypothyroidism, autoantibodies positive, and hyperthyroidism. RESULTS: A total of 1,225 participants with stable iodine prophylaxis and 3,946 without prophylaxis were enrolled. Of those participants, blood samples were available for 144 and 1,201 participants in the prophylaxis and no-prophylaxis groups, respectively. There were 17 (11.8%) and 146 cases (12.2%) of possible hypothyroidism or autoantibodies positive cases in the prophylaxis and no-prophylaxis groups, respectively, and there were no cases and 3 cases (0.2%) of possible hyperthyroidism in those two groups, respectively. Multivariable analysis for possible hypothyroidism revealed no association between stable iodine intake and possible hypothyroidism or autoantibodies positive [odds ratio 0.716 (95% confidence interval 0.399-1.284)] (p = 0.262). We did not perform multivariable analysis for hyperthyroidism due to the limited number of cases. CONCLUSION: Significant adverse effects of stable iodine intake on thyroid function were not observed among children and adolescents 7 years after the Fukushima Nuclear Disaster.

Prevención de morbilidades post-tiroidectomía total y subtotal: una revisión bibliográfica / Prevention of total and subtotal post-thyroidectomy morbidities: a bibliographic review

Las enfermedades tiroideas han presentado un auge en los últimos tiempos, aumentando consigo mismo el reporte de las intervenciones quirúrgicas. La tiroidectomía es una de las cirugías más practicadas en endocrinología y tras su realización se han descrito complicaciones, siendo éstas vinculadas a ciertos factores de riesgos que potencian su aparición. Se realizó búsqueda bibliográfica en el período comprendido entre febrero de 2018 a diciembre de 2019, en bases de datos internacionales (PubMed, Cochrane, SCIELO, LILACS y Redalyc) y búsqueda manual en Google Scholar, utilizando los términos complicaciones de tiroidectomías, complicaciones post-quirúrgicas, cirugía de tiroides y tiroidectomías. Se identificaron tres agrupaciones generales de factores de riesgo postquirúrgico: Factores intrínsecos de la enfermedad, comorbilidades del paciente y asociados al procedimiento quirúrgico. Es indispensable identificar y corregir comorbilidades para la prevención de complicaciones postquirúrgicas, puesto que las complicaciones continúan siendo una causa de considerable preocupación.

Specialist thyroid package 1 (PS1) in outpatient endocrine care [Pakiet specjalistyczny dotyczacy tarczycy (PS1) w ambulatoryjnej opiece endokrynologicznej].

The article presents the assumptions of a new specialist thyroid package (PS1) in outpatient specialist care in the field of endocrinology, which was introduced by the National Health Fund (NFZ - Narodowy Fundusz Zdrowia) from January 2020. It became an impulse to characterize the current problems affecting specialist care in the field of endocrinology, search for their potential causes and propose strategies that are intended to contribute to increasing the efficiency of the system.

Infliximab Therapy Could Decrease the Risk of the Development of Thyroid Disorders in Pediatric Patients With Crohn's Disease.

Autoimmune diseases, including autoimmune thyroid diseases (AITDs), may be associated with Crohn's disease (CD). Taking into consideration the role of tumor necrosis factor alpha (TNF-alpha) in the immune-mediated inflammation that underlies both diseases, we evaluated an ultrasound of thyroid gland in pediatric CD patients, naïve, and treated with infliximab (IFX), an anti-TNF-alpha antibody, to assess the risk for AITD and evaluated the usefulness of ultrasonography to diagnose AITD in patients with CD. Sixty-one patients with CD were enrolled in the study, including 36 patients (mean age 14.5 ± 3.5 years) treated with IFX (IFX group) for a mean of 13.9 ± 16.6 months and 25 patients (mean age 14.7 ± 2.3 years) who never received anti-TNF-alpha therapy (control group). An ultrasound examination of the thyroid gland was performed; thyroid function tests and thyroid antibodies were assessed. We found 10-times higher prevalence of decreased thyroid echogenicity in CD and IFX-naive patients compared to IFX-treated group [a significant reduction in thyroid echogenicity in 1/36 (2.8%) patients receiving IFX compared to 7/25 (28%) patients naive to biologic therapy]. The latter showed significantly lower thyroid-stimulating hormone (TSH) levels (p = 0.034) and higher levels of thyroid antibodies (p = 0.042) in comparison to control. Our data suggest the protective role of IFX therapy in the development of thyroid disorders and indicate the usefulness of thyroid ultrasound to identify the risk of probable AITD in pediatric patients with CD.

Lipid Complications after Hematopoietic Stem Cell Transplantation (HSCT) in Pediatric Patients.

HSCT (hematopoietic stem cell transplantation) is a widely applied method of treatment of pediatric patients with leukemia and other bone marrow-associated disorders. Metabolic disturbances can appear as procedure side effects. This study aimed to report incidence of lipid and thyroid disorders and time of their onset in pediatric patients after HSCT. There were 198 pediatric patients (123 males) aged 0.5-20 years who were subjected to HSCT. Patients were mostly diagnosed with Acute Leukemia (n = 190). The analysis of lipids, thyroid hormones, and thyroid antibodies levels comprised one month before the HSCT to last follow up visit between 2016 and 2019 (median 3.8 ± 1.8 years after HSCT). In males, the triglycerides levels increased over two times in the course of HSCT in both patients with initially low and elevated HDL (high-density lipoprotein) levels. Most of the lipid disorders occurred in six months after HSCT. Patients treated with L-thyroxine exhibited decreased LDL (low-density lipoprotein) levels. HDL remained at a lower level in males. Thyroid hormone abnormalities were evenly distributed in time until 4 years after HSCT. Patients require long term follow up including lipid metabolism and thyroid function analysis. HSCT survivors demand introduction of polyunsaturated fatty acids into the diet to reduce risk of developing the lipid complications.

Interference on Iodine Uptake and Human Thyroid Function by Perchlorate-Contaminated Water and Food.

BACKGROUND: Perchlorate-induced natrium-iodide symporter (NIS) interference is a well-recognized thyroid disrupting mechanism. It is unclear, however, whether a chronic low-dose exposure to perchlorate delivered by food and drinks may cause thyroid dysfunction in the long term. Thus, the aim of this review was to overview and summarize literature results in order to clarify this issue. METHODS: Authors searched PubMed/MEDLINE, Scopus, Web of Science, institutional websites and Google until April 2020 for relevant information about the fundamental mechanism of the thyroid NIS interference induced by orally consumed perchlorate compounds and its clinical consequences. RESULTS: Food and drinking water should be considered relevant sources of perchlorate. Despite some controversies, cross-sectional studies demonstrated that perchlorate exposure affects thyroid hormone synthesis in infants, adolescents and adults, particularly in the case of underlying thyroid diseases and iodine insufficiency. An exaggerated exposure to perchlorate during pregnancy leads to a worse neurocognitive and behavioral development outcome in infants, regardless of maternal thyroid hormone levels. DISCUSSION AND CONCLUSION: The effects of a chronic low-dose perchlorate exposure on thyroid homeostasis remain still unclear, leading to concerns especially for highly sensitive patients. Specific studies are needed to clarify this issue, aiming to better define strategies of detection and prevention.

Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies.

Nutraceuticals are defined as a food, or parts of a food, that provide medical or health benefits, including the prevention of different pathological conditions, and thyroid diseases, or the treatment of them. Nutraceuticals have a place in complementary medicines, being positioned in an area among food, food supplements, and pharmaceuticals. The market of certain nutraceuticals such as thyroid supplements has been growing in the last years. In addition, iodine is a fundamental micronutrient for thyroid function, but also other dietary components can have a key role in clinical thyroidology. Here, we have summarized the in vitro, and in vivo animal studies present in literature, focusing on the commonest nutraceuticals generally encountered in the clinical practice (such as carnitine, flavonoids, melatonin, omega-3, resveratrol, selenium, vitamins, zinc, and inositol), highlighting conflicting results. These experimental studies are expected to improve clinicians' knowledge about the main supplements being used, in order to clarify the potential risks or side effects and support patients in their use.

Anti-tumour necrosis factor α therapy - Does it increase the risk of thyroid disease or protect against its development?

AIM OF THE STUDY: Tumour necrosis factor α (TNF-α) is a cytokine involved in the pathogenesis of many diseases, primarily those associated with auto-immunisation. Anti-TNF-α drugs are used in the therapy of many of them, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, or inflammatory bowel disease. TNF-α is also a key factor in the pathogenesis of autoimmune thyroid disease (AITD). The incidence of AITD in people with other autoimmune diseases is increased compared to the general population. Therefore, it would be interesting to find out if anti-TNF-α therapy of other autoimmune diseases could influence the possible development or re-gression of thyroid gland dysfunction, especially AITD. AIM OF THE STUDY: The main aim of the study is to assess the effect of anti-TNF-α therapy used in inflammatory and immunological diseases on thyroid function and the development of AITD. CONCLUSIONS: The real impact of anti-TNF-α therapy on the development of AITD remains an open question. The available studies concern the adult population; there are no data regarding this problem in children. Due to the increasing use of anti-TNF-α therapy also in the paediatric population, it seems reasonable to evaluate this subject in this group of patients.

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.

Immunomodulatory effect of vitamin D and its potential role in the prevention and treatment of thyroid autoimmunity: a narrative review.

The main role of vitamin D is to control mineral homeostasis. However, recent studies suggested the existence of a number of extraskeletal effects. Among the latter, preclinical studies provided consistent data on the involvement of vitamin D in innate and adaptive immunity and autoimmunity. Molecular biology studies showed that both vitamin D receptor and vitamin D enzymatic complexes are expressed in a large number of cells and tissues unrelated to mineral homeostasis. In contrast, only a few randomized clinical trials in humans investigated the possible role of vitamin D in the prevention or treatment of immunological disorders. In this regard, low serum vitamin D levels have been reported in observational trials in human autoimmune disorders. The aim of the present paper was to review the potential implications of vitamin D in immune modulation, with special focus on thyroid autoimmune disorders.

Nutraceutical Supplements in the Thyroid Setting: Health Benefits beyond Basic Nutrition.

In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology-these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol-some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims to distinguish between the truths and myths surrounding the clinical use of such nutraceuticals.

Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the "SERENA study", a randomized, double-blind, placebo-controlled trial.

PURPOSE: Selenium is frequently in nutraceuticals for pregnancy, given its role on fertility and thyroid metabolism. However, most evidence rise from non-controlled studies. We aimed to evaluate the protective effect of selenium against thyroid autoimmunity during and after pregnancy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was performed and promoted by the Young Italian Endocrinologists Group (EnGioI)-Italian Society of Endocrinology. Forty-five women with thyroiditis in pregnancy were enrolled and randomly assigned to L-selenomethionine (L-Se-Met) 83 mcg/day or placebo (PLB) and evaluated at 10 ± 2 (T1), 36 ± 2 weeks of gestation (T2) and 6 months after delivery (postpartum, PP). RESULTS: We measured a significant reduction of autoantibodies after pregnancy in L-Se-Met group [at PP: TgAb 19.86 (11.59-52.60), p < 0.01; TPOAb 255.00 (79.00-292.00), p < 0.01], and an antibodies titer's rebound in PLB group (TgAb 151.03 ± 182.9, p < 0.01; TPOAb 441.28 ± 512.18, p < 0.01). A significant increase in selenemia was measured in L-Se-Met group at T2 (91.33 ± 25.49; p < 0.01) and PP (93.55 ± 23.53; p = 0.02). Two miscarriage occurred in PLB. No differences were found in thyroid volume, echogenicity, quality of life, maternal/fetal complications. CONCLUSIONS: SERENA study demonstrated a beneficial effect of L-Se-Met supplementation on autoantibody titer during pregnancy and on postpartum thyroiditis recurrence.

Thyroid and Cardiovascular Disease: Research Agenda for Enhancing Knowledge, Prevention, and Treatment.

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.