Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults.

Levothyroxine (LT4) is a safe, effective means of hormone replacement therapy for hypothyroidism. Here, we review the pharmaceutical, pathophysiological and behavioural factors influencing the absorption, distribution, metabolism and excretion of LT4. Any factor that alters the state of the epithelium in the stomach or small intestine will reduce and/or slow absorption of LT4; these include ulcerative colitis, coeliac disease, bariatric surgery, Helicobacter pylori infection, food intolerance, gastritis, mineral supplements, dietary fibre, resins, and various drugs. Once in the circulation, LT4 is almost fully bound to plasma proteins. Although free T4 (FT4) and liothyronine concentrations are extensively buffered, it is possible that drug- or disorder-induced changes in plasma proteins levels can modify free hormone levels. The data on the clinical significance of genetic variants in deiodinase genes are contradictory, and wide-scale genotyping of hypothyroid patients is not currently justified. We developed a decision tree for the physician faced with an abnormally high thyroid-stimulating hormone (TSH) level in a patient reporting adequate compliance with the recommended LT4 dose. The physician should review medications, the medical history and the serum FT4 level and check for acute adrenal insufficiency, heterophilic anti-TSH antibodies, antibodies against gastric and intestinal components (gastric parietal cells, endomysium, and tissue transglutaminase 2), and Helicobacter pylori infection. The next step is an LT4 pharmacodynamic absorption test; poor LT4 absorption should prompt a consultation with a gastroenterologist and (depending on the findings) an increase in the LT4 dose level. An in-depth etiological investigation can reveal visceral disorders and, especially, digestive tract disorders.

Relationship of Migraine and Tension-Type Headache With Hypothyroidism: A Literature Review.

BACKGROUND: Migraine, tension-type headache, and hypothyroidism constitute very common medical conditions. Headache is one of the most common symptoms of hypothyroidism, occurring in approximately one-third of the patients. To date, data about the relationship between migraine and tension-type headache and thyroid dysfunction, and in particular hypothyroidism have been contradictory, while the underlying pathophysiological basis explaining this association is still unclear. OBJECTIVE: In this review, we investigated the association between primary headaches and hypothyroidism, with the aim of shedding light on its pathophysiological basis. METHODS: We conducted a systematic search in the MEDLINE database using both subject headings and keywords for headache, migraine, tension-type headache, thyroid hormones, and hypothyroidism, and we also examined manually the reference lists of all articles that met the inclusion criteria. Included studies were related to headache and thyroid disease comorbidity, with emphasis on hypothyroidism (ideally demonstrated by hormonal measurements), and with the term headache including migraine, tension-type headache, and headache attributed to hypothyroidism (HAH) based on the International Classification of Headache Disorders IIIb. Quality of studies was assessed by the Newcastle-Ottawa scale. RESULTS: Of a total of 640 identified articles, 9 studies were included. Overall, there was vast heterogeneity across the included studies concerning population, study design and outcomes. Two studies investigated the HAH, with emphasis on the clinical characteristics of headache (time of onset, localization, quality, intensity, and response to hormonal replacement treatment). Five studies investigated comorbidity between migraine and thyroid disorders, especially hypothyroidism, and in the majority of them a positive association was demonstrated. One study found that headache, and particularly migraine, may increase the risk of developing hypothyroidism. Finally, only 1 study on chronic tension-type headache found coexistence of migraine and hypoactivity of the hypothalamus-pituitary-thyroid axis. The strengths and limitations of these studies are analyzed and possible pathophysiological mechanisms are suggested. CONCLUSIONS: The existing data are considered inadequate to answer with certainty the relationship between headaches and thyroid disorders. According to our analysis, it seems that suggestions for a possible bidirectional association between headaches and especially migraine and hypothyroidism could exist. It hence lays the foundation for further research into the aforementioned association and its pathogenesis via large prospective multicenter studies.

Impaired Metabolism of Selenomethionine in Graves' Disease: A Biokinetics Study of Soft Gel Capsule Formulation.

Patients with Graves' disease are known to have low selenium (Se) status, Se supplementation resulting in clinical and biochemical improvement. Selenomethionine (SeMet) in a new soft gel capsule formulation was used in a pilot study in 6 patients with acute Graves' disease and low selenium levels (61.3±12.9 µg/l) before and in 4/6 patients 3 months after combined treatment with methimazole and SeMet 200 µg/day (113.3±46.3 µg/l), as well as in 6 euthyroid controls (82±11.8 µg/l). The biokinetics were studied following ingestion of 200 µg SeMet (single dose) soft gel capsule, Se serum concentrations being measured at various time points within 24 h. Se levels rose variably in all patients and controls. While levels peaked in all subjects following 8 h of intake, the increase was somewhat slower in acute hyperthyroidism as compared to 3 months later when these patients had been rendered euthyroid, this possibly due to derangement of Se storage capacity by SEPP or increased requirements in the acute phase of the disease, leading to depletion of the trace element. The compound was shown to be bioavailable and safe and patients treated for 3 months exhibited higher Se levels at the different time points. These findings are of major importance for sufferers of GD since they indicate that early Se supplementation, with its beneficial antioxidant impact on inflammatory activity, could slow, or possibly even forestall, the clinical progression of the disease.

Toxic chemicals and thyroid function: hard facts and lateral thinking.

Increasing quantities of evidence-based data incriminate a large number of environmental pollutants for toxic effects on the thyroid. Among the many chemical contaminants, halogenated organochlorines and pesticides variably affect the hypothalamic-pituitary-thyroid axis and disrupt thyroid function. PCBs and their metabolites and PBDEs bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Meanwhile, at the molecular level, PCB congeners may activate phosphorylation of Akt, p-Akt, and forkhead box O3a (FoxO3a) protein resulting in inhibition of the natrium/iodide symporter. Given therefore the growing concern developing around these multiple toxic chemicals today invading numerous environments and their long-term deleterious effects not only on the thyroid but also on general health, we strongly advocate their strict regulation and, moreover, their gradual reduction. A good degree of "lateral thinking", we feel, will lead to a use of chemicals that will enhance life while concurrently carefully protecting the environment.

The effect of Greek herbal tea consumption on thyroid cancer: a case-control study.

BACKGROUND: Although in the last decade several studies have addressed the protective role of black and green tea on several diseases, including cancer, there are only few and controversial studies on the effect of tea on benign and malignant thyroid diseases. METHODS: An age and gender group matched case-control study conducted in Athens, Greece, was designed. 113 Greek patients with histologically confirmed thyroid cancer and 286 patients with benign thyroid diseases along with 138 healthy controls were interviewed with a pre-structured questionnaire in person by trained interviewers. RESULTS: An inverse association between chamomile tea consumption and benign/malignant thyroid diseases was found (P < 0.001). The odds of chamomile tea consumption, two to six times a week, after controlling for age, gender and BMI, were 0.30 (95% CI: 0.10-0.89) and 0.26 (95% CI: 0.12-0.5) for developing thyroid cancer and benign thyroid diseases, respectively when compared with not consumption. The duration of consumption was also inversely associated with the diseases. Thirty years of consumption significantly reduced the risk of thyroid cancer and benign thyroid diseases development by almost 80%. Similar, although weaker protective association, was found for sage and mountain tea. Adjustment for smoking, alcohol and coffee consumption did not alter the results. CONCLUSIONS: Our findings suggest for the first time that drinking herbal teas, especially chamomile, protects from thyroid cancer as well as other benign thyroid diseases.

The ETA-ESE statement on the European Chemicals Agency opinion on iodine as an endocrine disruptor.

In 2022, the European Chemicals Agency (ECHA) made a statement concluding that iodine is an endocrine disruptor (ED). "We stress the fact that the ECHA opinion ECHA/BPC/357/2022 is based on their misguidedly zooming in on exclusively the biocidal products (e.g., hand disinfectants, disinfection of animals' teats/udder, embalming fluids before cremation, etc.) that contain molecular iodine (I2), entirely neglecting [see the 2013 ECHA Regulation (EU) n°528/2012 describing iodine as being of "great importance for human health". Clearly, the current sweeping and erroneous classification of "iodine" as an endocrine disruptor is ill-advised. We moreover call upon the scientific and medical community at large to use the accurate scientific nomenclature, i.e., iodide or iodate instead of "iodine" when referring to iodized salts and food prepared there with. Drugs, diagnostic agents, and synthetic chemicals containing the element iodine in the form of covalent bonds must be correctly labelled ''iodinated'', if possible, using each time their distinctive and accurate chemical or pharmacological name.

EMAS position statement: Thyroid disease and menopause.

INTRODUCTION: Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS: This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.

Nutrition and thyroid disease.

PURPOSE OF REVIEW: The aim of this review was to determine, based on the most recent findings, the involvement of trace elements and vitamins critical for thyroid function and combating thyroid disease. RECENT FINDINGS: Nutritional guidance is pivotal to reducing the risk of thyroid disease and to managing it when it arises, this meaning the prescription of diets rich in such micronutrients as iodine, selenium, iron, zinc, and vitamins B12, D3, and A. Most of the above micronutrients are good antioxidants, building up an anti-inflammatory profile, reducing thyroid autoantibodies and body fat, and improving thyroid function. Diets are increasingly being prescribed, especially for those suffering from Hashimoto's thyroiditis. Notable among prescribed diets is the Mediterranean diet. Rich in critical elements, it benefits patients at the immune endocrine and biomolecular levels. SUMMARY: Importantly, it is likely that widespread adherence to the Mediterranean diet, together with a reduction of meat consumption and potential elimination of gluten and lactose may improve inflammation and have an impact on public health while possibly diminishing thyroiditis symptoms. It is hoped that this review can direct policymakers towards undertaking cost-effective interventions to minimize deficiency of essential minerals and vitamins and thus protect both general and thyroid health.

A systematic review and meta-analysis investigating the relationship between metabolic syndrome and the incidence of thyroid diseases.

PURPOSE: To assess the prospective association between metabolic syndrome (MetS), its components, and incidence of thyroid disorders by conducting a systematic review and meta-analysis. METHODS: A systematic search was performed in Ovid Medline, Embase.com, and Cochrane CENTRAL from inception to February 22, 2023. Publications from prospective studies were included if they provided data on baseline MetS status or one of its components and assessed the incidence of thyroid disorders over time. A random effects meta-analysis was conducted to calculate the odds ratio (OR) for developing thyroid disorders. RESULTS: After full-text screening of 2927 articles, seven studies met our inclusion criteria. Two of these studies assessed MetS as an exposure (N = 71,727) and were included in our meta-analysis. The association between MetS at baseline and incidence of overt hypothyroidism at follow-up yielded an OR of 0.78 (95% confidence interval [CI]: 0.52-1.16 for two studies, I2 = 0%). Pooled analysis was not possible for subclinical hypothyroidism, due to large heterogeneity (I2 = 92.3%), nor for hyperthyroidism, as only one study assessed this association. We found evidence of an increased risk of overt (RR: 3.10 (1.56-4.64, I2 = 0%) and subclinical hypothyroidism (RR 1.50 (1.05-1.94), I2 = 0%) in individuals with obesity at baseline. There was a lower odds of developing overt hyperthyroidism in individuals with prediabetes at baseline (OR: 0.68 (0.47-0.98), I2 = 0%). CONCLUSIONS: We were unable to draw firm conclusions regarding the association between MetS and the incidence of thyroid disorders due to the limited number of available studies and the presence of important heterogeneity in reporting results. However, we did find an association between obesity at baseline and incidence of overt and subclinical hypothyroidism.

The clinical significance of low dose biotin supplements (<300µg/day) in the treatment of patients with hypothyroidism: crucial or overestimated?

BACKGROUND: In the last decade, the combination of the widespread use of streptavidin-biotin technology and biotin-containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 µg/day. METHODS: Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300µg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS. RESULTS: A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation. CONCLUSION: Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don't occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.

The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities.

This review addresses the role of the essential trace element, selenium, in type-2 diabetes mellitus (T2DM) and its metabolic co-morbidities, i.e., metabolic syndrome, obesity and non-alcoholic fatty liver disease. We refer to the dietary requirements of selenium and the key physiological roles of selenoproteins. We explore the dysregulated fuel metabolism in T2DM and its co-morbidities, emphasizing the relevance of inflammation and oxidative stress. We describe the epidemiology of observational and experimental studies of selenium in diabetes and related conditions, explaining that the interaction between selenium status and glucose control is not limited to hyperglycemia but extends to hypoglycemia. We propose that the association between high plasma/serum selenium and T2DM/fasting plasma glucose observed in many cross-sectional studies may rely on the upregulation of hepatic selenoprotein-P biosynthesis in conditions of hyperglycemia and insulin resistance. While animal studies have revealed potential molecular mechanisms underlying adverse effects of severe selenium/selenoprotein excess and deficiency in the pathogenesis of insulin resistance and ß-cell dysfunction, their translational significance is rather limited. Importantly, dietary selenium supplementation does not appear to be a major causal factor for the development of T2DM in humans though we cannot currently exclude a small contribution of selenium on top of other risk factors, in particular if it is ingested at high (supranutritional) doses. Elevated selenium biomarkers that are often measured in T2DM patients are more likely to be a consequence, rather than a cause, of diabetes.

On the Centennial of Vitamin D-Vitamin D, Inflammation, and Autoimmune Thyroiditis: A Web of Links and Implications.

The 100th anniversary of the discovery of vitamin D3 (VitD3) coincides with significant recent advances in understanding its mechanism of action along with accumulating knowledge concerning its genomic and nongenomic activities. A close relationship between VitD3 and the immune system, including both types of immunity, innate and adaptive, has been newly identified, while low levels of VitD3 have been implicated in the development of autoimmune thyroiditis (AIT). Active 1,25(OH)2 D3 is generated in immune cells via 1-α-hydroxylase, subsequently interacting with the VitD3 receptor to promote transcriptional and epigenomic responses in the same or adjacent cells. Despite considerable progress in deciphering the role of VitD3 in autoimmunity, its exact pathogenetic involvement remains to be elucidated. Finally, in the era of coronavirus disease 2019 (COVID-19), brief mention is made of the possible links between VitD3 deficiency and risks for severe COVID-19 disease. This review aims to commemorate the centennial of the discovery of VitD3 by updating our understanding of this important nutrient and by drawing up a framework of guidance for VitD3 supplementation, while emphasizing the necessity for personalized treatment in patients with autoimmune thyroid disease. A tailored approach based on the specific mechanisms underlying VitD3 deficiency in different diseases is recommended.

Metabolic, Oxidative and Psychological Stress as Mediators of the Effect of COVID-19 on Male Infertility: A Literature Review.

Over 300 million patients with coronavirus disease 2019 (COVID-19) have been reported worldwide since the outbreak of the pandemic in Wuhan, Hubei Province, China. COVID-19 is induced by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effect of SARS-CoV-2 infection on the male reproductive system is unclear. The aim of this review is to assess the effect of SARS-CoV-2 infection on male fertility and the impact of possible mediators, such as metabolic, oxidative and psychological stress. SARS-CoV-2 infection aggravates metabolic stress and directly or indirectly affects male fertility by reducing seminal health. In addition, SARS-CoV-2 infection leads to excessive production of reactive oxygen species (ROS) and increased psychological distress. These data suggest that SARS-CoV-2 infection reduces male fertility, possibly by means of metabolic, oxidative and psychological stress. Therefore, among other consequences, the possibility of COVID-19-induced male infertility should not be neglected.

How to approach clinically discordant FT4 results when changing testing platforms: real-world evidence.

PURPOSE: Measurement of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) is important for assessing thyroid dysfunction. After changing assay manufacturer, high FT4 versus TSH levels were reported at Ente Ospedaliero Cantonale (EOC; Bellinzona, Switzerland). METHODS: Exploratory analysis used existing TSH and FT4 measurements taken at EOC during routine clinical practice (February 2018-April 2020) using Elecsys® TSH and Elecsys FT4 III immunoassays on cobas® 6000 and cobas 8000 analyzers (Roche Diagnostics). Reference intervals (RIs) were estimated using both direct and indirect (refineR algorithm) methods. RESULTS: In samples with normal TSH levels, 90.9% of FT4 measurements were within the normal range provided by Roche (12-22 pmol/L). For FT4 measurements, confidence intervals (CIs) for the lower end of the RI obtained using direct and indirect methods were lower than estimated values in the method sheet; the estimated value of the upper end of the RI (UEoRI) in the method sheet was within the CI for the UEoRI using the direct method but not the indirect method. CIs for the direct and indirect methods overlapped at both ends of the RI. The most common cause of increased FT4 with normal TSH was identified in a subset of patients as use of thyroxine therapy (72.6%). CONCLUSIONS: It is important to verify RIs for FT4 in the laboratory population when changing testing platforms; indirect methods may constitute a convenient tool for this. Applying specific RIs for selected subpopulations should be considered to avoid misinterpretations and inappropriate clinical actions.

New insights into subclinical hypothyroidism and cardiovascular risk.

Subclinical hypothyroidism (SH) is a frequent condition affecting millions of people around the world. Defined by increased thyrotropin-stimulating hormone (TSH) and accompanied by normal thyroid hormone levels, SH reflects a mild tissue hypothyroidism that has been associated with metabolic derangements and-although this issue is still contentious-possibly with increased cardiovascular risk. Depending on the degree of TSH elevation, SH has accordingly been associated with hyperlipidemia, arterial hypertension, and cardiovascular disease (CVD), as well as, increasingly, newly emerging CVD risk factors such as serum C-reactive protein and retinol binding protein 4 levels. There have also been reports of abnormalities in glucose metabolism and of hemostatic parameters, mainly underscored by the increased activity of factor VII. This review discusses the results of the latest studies on the various parameters affected by SH while highlighting the need for timely treatment with levothyroxine.

The interface between thyroid and diabetes mellitus.

Thyroid disease and type 1 but also type 2 diabetes mellitus (DM) are strongly associated, and this has important clinical implications for insulin sensitivity and treatment requirements. The pathophysiological basis of this association has only recently been better elucidated. It rests on a complex interaction of common signalling pathways and, in the case of type 1 diabetes and autoimmune thyroid disease, on a linked genetic susceptibility. The pathophysiological mechanisms underlying this linked regulation are increasingly being unravelled. They are exemplified in the regulation of 5' adenosine monophosphate-activated protein kinase (AMPK), a central target not only for the modulation of insulin sensitivity but also for the feedback of thyroid hormones on appetite and energy expenditure. The present review will discuss these concepts and their consequences for the clinical care of patients with DM and thyroid disorders. Moreover, it makes reference to the added effect of metformin in suppressing TSH.

Aging and the hypothalamic-pituitary-thyroid axis.

The world's population is increasingly aging, this noted particularly in the Western world where there are ever greater numbers of centenarians and those over 85 years. Given the immense importance of the thyroid gland for optimal health and the fact that morphological and functional changes in the hypothalamic-pituitary-thyroid (HPT) axis take place as a natural adaptation to the aging process, a clear distinction must be made in older individuals between these and the onset of disease. However, this is problematic since, frequently, subtle differences exist between them, making diagnosis a challenging task, especially as concerns subclinical disease. The newly emerging interdisciplinary field of geroscience offers the prospect of being used as a platform to investigate the effect of disrupted HPT function on functional capacity and cognitive ability among the aged, as well as the risk or onset of age-associated diseases, thus enhancing healthspan and lifespan. Because optimal functioning of the thyroid gland is a prerequisite for longevity as well as for mental and physical wellbeing, this review summarizes the recent scientific data regarding HPT and aging while discussing alternative and personalized treatment approaches to maintaining a healthy thyroid as a means to ensuring a long, active, and healthy life.

COVID-19 and Thyroid Diseases: A Bidirectional Impact.

CONTEXT: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has become the most lethal and rapidly moving pandemic since the Spanish influenza of 1918-1920, is associated with thyroid diseases. METHODS: References were identified through searches of PubMed and MEDLINE for articles published from Jan 1, 2019 to February 19, 2021 by use of the MeSH terms "hypothyroidism", "hyperthyroidism", "thyroiditis", "thyroid cancer", "thyroid disease", in combination with the terms "coronavirus" and "COVID-19". Articles resulting from these searches and references cited in those articles were reviewed. RESULTS: Though preexisting autoimmune thyroid disease appears unlikely to render patients more vulnerable to COVID-19, some reports have documented relapse of Graves' disease (GD) or newly diagnosed GD about 1 month following SARS-CoV-2 infection. Investigations are ongoing to investigate molecular pathways permitting the virus to trigger GD or cause subacute thyroiditis (SAT). While COVID-19 is associated with non-thyroidal illness, it is not clear whether it also increases the risk of developing autoimmune hypothyroidism. The possibility that thyroid dysfunction may also increase susceptibility for COVID-19 infection deserves further investigation. Recent data illustrate the importance of thyroid hormone in protecting the lungs from injury, including that associated with COVID-19. CONCLUSION: The interaction between the thyroid gland and COVID-19 is complex and bidirectional. COVID-19 infection is associated with triggering of GD and SAT, and possibly hypothyroidism. Until more is understood regarding the impact of coronavirus on the thyroid gland, it seems advisable to monitor patients with COVID-19 for new thyroid disease or progression of preexisting thyroid disease.

Selenium and at-risk pregnancy: challenges and controversies.

Selenium (Se), an essential trace element, is inserted as selenocysteine into an array of functional proteins and forms the core of various enzymes that play a cardinal role in antioxidant defense mechanisms, in redox regulation, and in thyroid hormone metabolism. Variations in plasma Se are due to nutritional habits, geographic and ethnic differences, and probably to genetic polymorphisms, the latter still to be conclusively established. Se concentrations were reported to be low in women of reproductive age in the UK, decreasing further during pregnancy, this resulting in low plasma and placental antioxidant enzyme activities. Since low serum Se levels have been found in women with preeclampsia, it has been hypothesized that low maternal Se status during early gestation may be an indicator of preterm birth. Moreover, it is documented that Se administration during pregnancy tendentially reduced the markers of thyroid autoimmunity and the incidence of maternal hypothyroidism in the postpartum period. Importantly, low Se levels in pregnant women affect fetal growth and augment the risk of delivering a small-for-gestational age infant by reducing placental antioxidant defense, while low Se in the third trimester is thought to indicate increased demands by the placenta, an issue which requires further confirmation. There is evidently a need for double-blind, placebo-controlled studies to better determine the efficacy and safety of Se supplementation in pregnancy at high risk for complications, and for measurement of Se levels or of selenoprotein P, the most reliable parameter of Se status, particularly in selenopenic regions.

50 years of the ETA: "the selenium connection".

The recent celebration of the 50 years of the ETA closely coincided with that of the 200 years since the discovery and description of selenium, an essential trace element for normal thyroid gland function and thus an adjuvant in the treatment of thyroid diseases. The aim of this commentary is to briefly outline the half centennial of the ETA while also signaling important moments in the history of selenium, developments in its availability round the world, details of its connection with thyroid function and, finally, its current and projected modes of application.