Mild Graves Research Articles

6662 Effect of Selenium Supplementation on Mild Graves’ Ophthalmopathy at a Tertiary Hospital - A Six-Month Open-Labelled, Assessor-Masked, Randomized-Controlled Trial

Abstract Disclosure: J.M. Flores: None. N.G. Sioson: None. J.D. Uy-Ho: None. A.L. Suller-Pansacola: None. Graves’ orbitopathy is associated with increased oxidative stress. Selenium, with its antioxidant and immunoregulatory actions, has been proposed as an adjuvant therapy. Objective: This study was undertaken to determine whether selenium supplementation for six months can decrease signs and prevent worsening of mild Graves ophthalmopathy among Filipinos. Methods: We conducted an open-labelled, assessor-masked, Randomized-Controlled Trial on patients with mild Graves’ ophthalmopathy wherein one arm was assigned to standard of care (eye drops) only for a period of six months while another arm was assigned to 200 ug/day oral Selenium supplementation alongside standard of care. Population: Adult patients with Graves’ hyperthyroidism, with at least one sign of mild ophthalmopathy with GO disease duration of less than 18 months Results: Independent Sample T-test, Mann-Whitney U test and Fisher’s Exact/Chi-square test were used to determine the difference of mean, rank and frequency, between patients given Selenium versus patients given standard of care. Paired Sample T-test, Wilcoxon Sign rank test and McNemar test were used to determine the difference of mean, rank and frequency on patients from initial to 3rd month or 6th month observation. Null hypotheses were rejected at 0.05α-level of significance. There was a significant difference in Clinical Activity Score (CAS) between patients given selenium supplementation and those assigned to standard of care. On initial examination for the Selenium group, 14 eyes (33.33%) had a CAS score of 0, which increased to 27 eyes (64.29%) on the third month and ended to a 26 eyes (61.9%) at the sixth month of treatment. For the non-selenium group, 11 eyes had a CAS score of zero initially, increased to 16 eyes (and 38.1%) then finally arrived to a total count of 14 eyes (33.33%). Improvement in CAS may be attributed specifically to improvement in caruncle/plical swelling showing a significant difference (p-value 0.040). Comparing the two groups, a statistical significance in CAS is noted between the treatment versus the control group with a p-value of 0.017 on the 6th month. Conclusion: Selenium supplementation provided significant benefit in terms of decreasing signs and preventing worsening of mild GO through improved CAS score. Further studies exploring the baseline and end of treatment selenium concentrations in the Philippines may be warranted. Presentation: 6/3/2024

8640 Thyroid Orbitopathy in Pregnancy

Abstract Disclosure: Z. Maisonet -Feliciano: None. M. Alvarado: None. L.A. Gonzalez-Rodriguez: None. M. Ramirez: None. L. El Musa Penna: None. J. Segarra-Villafane: None. I.C. Arroyo: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. Thyroid orbitopathy, often associated with Graves' disease, is characterized by the inflammation and swelling of ocular tissues. Its occurrence or exacerbation during pregnancy is infrequent, primarily due to the immunosuppressive state inherent in pregnancy. In most instances, the immunosuppression associated with pregnancy leads to a reduction in TRAb levels, although they continue to be present in women who have an active form of the disease. The course and severity of ocular manifestation do not always correlate with thyroid hormone levels. Strict control of thyroid function is crucial in patients with thyroid eye disease. This report sheds light on the rare occurrence of thyroid orbitopathy during pregnancy, a condition that complicates treatment due to potential risks to both the mother and the child. In this case, a 35-year-old pregnant woman with no prior history of thyroid issues exhibited symptoms of hyperthyroidism in her first trimester, including unintended weight loss, anxiety, and tremors in the upper limbs. She also presented with ocular discomfort, diplopia, and eyelid lag. Thyroid tests confirmed Graves Disease, with a significant elevation in Thyroid Stimulating Immunoglobulin (TSI): 243 %, Free thyroxine (T4): 1.08 ng/dl and Triiodothyronine (T3): >1.89 units and decreased Thyroid Stimulation Hormone (TSH): 0.001 uIU/ml. Ophthalmic examination revealed mild Graves orbitopathy due to bilateral exophthalmos (measured by Hertel’s exophthalmometer) 21mm on both sides, Marginal reflex distance (MDR) 1: right eye 9 mm and left 7mm. MDR 2: right eye 6mm and left eye 7mm. Right upper eyelid retraction, lagophthalmos of the right eye, limitation in the upward movement of the left eye, and vertical diplopia on extreme gazes without signs of orbital compression. Considering her normal FT4 levels and the mild nature of her hyperthyroidism, the decision was made to prioritize the mother's treatment while minimizing fetal risk, thus opting not to initiate antithyroid medication but to closely monitor her thyroid function. Symptomatic management of her orbitopathy was provided including lubricating eye drops and an eye patch. Throughout the progression of her pregnancy, her TSI levels exhibited a decreasing trend while FT4 remained within normal limits. Following delivery, there was a notable improvement in her ocular symptoms, and her TSH started increasing up to normal values of 1.29 uIU/ml and FT4 remained in range. This report underscores the importance of recognizing uncommon presentations of autoimmune thyroid conditions, such as thyroid orbitopathy, during pregnancy. It emphasizes the complexities and necessary considerations in treating these cases. A collaborative approach involving endocrinology, ophthalmology, and obstetrics is essential to safeguard the health of both the mother and the fetus. Presentation: 6/1/2024

Characteristics of Dry Eye Syndrome in Patients with Mild Graves’ Ophthalmopathy

Characteristics of Dry Eye Syndrome in Patients with Mild Graves’ Ophthalmopathy

FRI484 Assessment Of Early-trimester Maternal Thyroid Function And Iodine Nutritional Status Of Pregnant Women In Northern Taiwan

Abstract Disclosure: G. Su: None. C. Yeh: None. C. Yang: None. C. Hwu: None. H. Chen: None. F. Wang: None. C. Huang: None. Background: The American Thyroid Association (ATA) has proposed to lower the early-trimester upper limit of the TSH reference interval to become 0.5 mIU/L less than the non-pregnant value. The local-regional reference intervals in Taiwan is unknown. The aim of the study is to evaluate the early-trimester thyroid function and iodine nutritional status of pregnant women in Taiwan. Methods: Women aged ≥20 years-old and in gestation 8 to 15 weeks were recruited in Taipei Veterans General Hospital from March 2019 to July 2022. Thyroid function and antibodies, including TSH, free T4, free T3, total T4, total T3, anti-thyroglobulin antibody (aTG) and anti-thyroidperoxidase antibody (aTPO), TSH receptor antibody, were measured. The gestation-specific thyroid function reference range was derived from the 2.5th and 97.5th percentiles of the studied women. Random spot urine sample was collected and urinary iodine concentration was checked by inductively coupled plasma mass spectrometry. A simple food frequency questionnaire was also completed. Results: A total of 211 women were enrolled and the derived early-trimester upper limit of serum TSH (median: 0.92 [0.007-3.08] uIU/mL) was lower than the value provided by the manufacturer (0.27-4.2 uIU/mL), while the upper limit of free T4 (median: 1.28 [0.93-2.15] ng/dL) and free T3 (3.00 [2.30-5.10]ng/dL) were both higher than the non-pregnant value (0.93-1.7 ng/dL and 2.0-4.4 ng/dL, respectively). The range of total T4 (median: 9.90 [6.39-15.36] ng/dL) and total T3 (median: 136 [89.50-223.20] ng/dL) in the studied women were similar to the non-pregnant range (5.1-14.1 ng/dL and 80-200 ng/dL, respectively). The positivity rate of aTG & aTPO were 8.6%. Two patients with mild Graves’ disease and three patients with subclinical hypothyroidism were incidentally detected and treated. The positive predictive value for detecting thyroid dysfunction using the non-pregnant reference interval was only 15.9% because subclinical hyperthyroidism (18.2%, n=37) would be over-diagnosed and subclinical hypothyroidism (1.0%, n=2) would be under-diagnosed. The overall median UIC was 160.9 μg/L, indicating a sufficient iodine status. Dairy products were the most commonly consumed iodine-containing food type with 71.8% of the pregnant women ingesting dairy products ≥3 days/week. The median intake frequency for seaweed, fish, and seafood were one day per week. Approximately 34.0% of the women took multivitamin every day, but 58.4% of the women never took multivitamin. Conclusion: Our results indicate that the iodine nutritional status in the early trimester of pregnancy is adequate and that the upper limit of serum TSH was approximately 1.12 uIU/mL lower than the upper limit provided by the manufacturer. Gestation-specific thyroid function reference intervals are needed for correct diagnosis of thyroid dysfunction in pregnancy. Presentation: Friday, June 16, 2023

Efficacy of selenium supplementation for mild-to-moderate Graves’ ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial

BackgroundThe therapeutic effect of selenium has been demonstrated in mild Graves’ ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea.MethodsThe SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19 years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6 months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6 months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3 months, clinical activity of GO at 3 and 6 months, thyroid autoantibody titers at 3 and 6 months, and the response rate at 3 and 6 months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6.DiscussionThe SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO.Trial registrationKCT0004040. Retrospectively registered on 5 June 2019. https://cris.nih.go.kr/cris/search/detailSearch.do/14160.

Survey on selenium clinical supplementation in autoimmune thyroid disease.

Previous trials show that selenium could be a very useful tool in the control and treatment of autoimmune thyroid diseases. In this cross-sectional study, through a survey, we aim to evaluate Portuguese endocrinologists' perception and pattern of prescription of selenium supplements in these diseases and verify its agreement with current guidelines. The endocrinologists registered in the Portuguese Medical Association were sent an email with a web-based questionnaire, regarding their knowledge and use of selenium supplements in thyroid autoimmune pathology. A total of 105 physicians (33% of the total) submitted the survey. The selenium serum concentration in the general population was unknown to 80% of respondents. Over a third of respondents have never prescribed selenium for autoimmune thyroid disease. However, 89% are not afraid of recommending it, and 61% indicate Graves' orbitopathy as the pathology they would supplement. In Hashimoto's thyroiditis, 36% of respondents use selenium occasionally or frequently, and this percentage rises to 60% in Graves' disease. Although recommendations only encompass mild Graves' orbitopathy, selenium is prescribed across the spectrum of autoimmune thyroid diseases, probably due to recent studies that consistently show improvement of biochemical hallmarks in these patients. Further investigation is required on the impact of selenium supplements on primarily clinical outcomes and to identify disorders and/or patients who will benefit the most. Also, there is still insufficient knowledge of this field in the medical community, and evidence-based practice should continue to be promoted by endocrinology societies.

Coexistent Papillary Thyroid Carcinoma in a Patient with Graves' Disease

A 21-year-old male presented with the features of thyrotoxicosis, and his thyroid function tests revealed primary hyperthyroidism. He also had mild bilateral exophthalmos with lid lag, lid retraction, and a clinical activity score of 1, suggestive of mild Graves' ophthalmopathy. Neck ultrasonography revealed mild diffuse goiter with bilateral fairly large nodules predominantly at the right lobe and bilateral multiple cervical lymphadenopathies. Tc-99m pertechnetate scan demonstrated diffuse goiter with homogeneously increased radiotracer concentration. He had an elevated titer of thyroid-stimulating hormone receptor autoantibody level. Fine-needle aspiration cytology from the largest nodule of the right lobe reported a Bethesda Category-VI lesion compatible with papillary thyroid carcinoma. Graves' disease and papillary thyroid cancer carcinoma might be present concomitantly in the same patient. Although links between these entities have long been investigated, a clear correlation is not established yet.

PSAT353 Can Generalized Granuloma Annulare occur in patients with Graves’ disease?

Abstract Introduction Granuloma annulare (GA) is a benign self-limiting dermatosis, typically characterized by an annular arrangement of erythematous or flesh-colored papules, affecting patients of all ages. An association between GA and autoimmune diseases (including autoimmune thyroiditis) has been reported in the literature thus suggesting that GA belongs to the spectrum of autoimmune diseases. However, only a few case reports described the unusual association of localized GA with hyperthyroidism. The definitive correlation between thyroid disease and GA hasn't been established. It was suggested that there is a common immunogenic predisposition or that both diseases share a common pathway. We present a rare case of generalized granuloma annulare in a patient with Graves’ disease. Case report A 52-year-old African American female with a past medical history of Graves’ disease with mild Graves’ ophthalmopathy was referred to the endocrinology clinic. She was diagnosed with Graves’ disease seven years ago and was medically managed ever since. Initially, she was treated with a high dose of methimazole however, for the past six years, she was on a stable dose of methimazole 5 mg daily. Two years following diagnosis of Graves’ disease, she developed serpiginous non-pruritic erythematous skin papules and patches in the right upper arm which slowly progressed over the course of years to involve bilateral inner thighs and under the breasts. She was evaluated by dermatology at that time and was empirically treated with a topical antifungal agent without any significant improvements. After establishing care with us, there was suspicion of methimazole-induced ANCA vasculitis or other autoimmune diseases. Extensive rheumatological workup including ANCA level was performed with negative results. Since her thyroid function tests (TSH and free T4) were normal on a low dose of methimazole for an extended period, we discontinued methimazole, however, skin rash didn't improve. The patient was then evaluated by dermatology and was diagnosed with GA based on clinical judgment. She was subsequently treated with an extended course of triple antibiotics therapy using rifampin, ofloxacin, and minocycline for 5 months with significant improvement of the skin rash. Currently, the patient has been off methimazole for 12 months and off triple antibiotic for 4 months with no recurrence of symptoms. Conclusion Although rare, generalized granuloma annulare can be seen in patients with autoimmune thyroid disease including Graves’ disease. Hence, endocrinologists should be aware of the different skin manifestations which can be seen in patients with autoimmune thyroid disease. Further studies are necessary to clarify the association of GA with autoimmune thyroid disease. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

2021 Asia-Pacific Graves' Disease Consortium Survey of Clinical Practice Patterns in the Management of Graves' Disease.

Although Graves' disease (GD) is common in endocrine practices worldwide, global differences in diagnosis and management remain. We sought to assess the current practices for GD in countries across Asia and the Pacific (APAC), and to compare these with previously published surveys from North America and Europe. A web-based survey on GD management was conducted on practicing clinicians. Responses from 542 clinicians were received and subsequently analysed and compared to outcomes from similar surveys from other regions. A total of 542 respondents participated in the survey, 515 (95%) of whom completed all sections. Of these, 86% were medical specialists, 11% surgeons, and 3% nuclear medicine physicians. In addition to serum thyroid-stimulating hormone (TSH) and free thyroxine assays, most respondents would request TSH-receptor autoantibody (TRAb) measurement (68%) during initial work-up. Thyroid ultrasound is requested by about half of respondents (53%), while the use of nuclear medicine scans is limited. The preferred first-line treatment is anti-thyroid drug (ATD) therapy (79%) with methimazole (MMI) or carbimazole (CBZ), followed by radioiodine (RAI; 19%) and surgery (2%). In case of surgery, one-third of respondents would opt for a subtotal rather than a total thyroidectomy. In case of mild Graves orbitopathy (GO), ATDs (67%) remains the preferred treatment, but a larger proportion of clinicians prefer surgery (20%). For a patient with intention to conceive, the preferred treatment pattern remained unchanged, although propylthiouracil (PTU) became the preferred ATD-agent during the first trimester. In comparison to European and American practices, marked differences were noted in the relatively infrequent usage of nuclear medicine scans and the overall higher use of a ATDs and β-blockers and adjunctive ATD-treatment during RAI in the APAC-group. Although regional differences regarding the diagnosis and management of GD are apparent in this first pan-Asia-Pacific survey, this study reveals the overall approach to the management of this disease in Asia-Pacific generally tends to fall between the trends appreciated in the American and European cohorts.

Relative selenium insufficiency is a risk factor for developing severe Graves’ orbitopathy: a case–control study

Background/aimsSelenium (Se), an antioxidant agent, is effective in preventing mild Graves’ orbitopathy (GO) deterioration. However, the significant risk of low serum Se concentration for GO progression has not been identified....

Oral selenium improved the disease activity in patients with mild Graves’ orbitopathy

Graves' orbitopathy (GO) is the most common extrathyroidal manifestation of Graves' disease (GD), an autoimmune disorder arising from the activity of T lymphocytes against antigens that infiltrate thyroid tissue, orbital tissue and extraocular muscles. An increase in oxidative stress has been discovered in autoimmune thyroid disease, encouraging investigation into new forms of treatment. Selenium has been described as a treatment option given its antioxidant properties. The present study evaluates the decrease of progression and inflammatory signs in patients with mild GO with oral selenium supplementation. Controlled, randomized, single center trial at an ophthalmology referral center in Mexico City. Patients at least 18years of age with mild GO according to the CAS classification were included; exclusion criteria in addition to corticosteroid treatment included smokers or selenium allergy. Each patient was randomized into one of two groups. Group A took placebo tablets which consisted of 100μg of starch twice a day for 6months, and group B took a 100μg selenium tablet twice a day for 6months. The patients from both groups were examined and evaluated using a CAS score before and after the first, third and sixth month of treatment. Thirty eyes of 30 patients were studied. The pretreatment values showed no statistically significant differences between groups (P>0.05). Intergroup analysis showed statistically significant differences in palpebral fissure and CAS score between the pretreatment values and six months after treatment in the selenium group (P<0.05). No differences were found in any variables in the placebo group during the study period (P>0.05). No adverse events were reported. This is the first study in a Mexican population demonstrating that oral selenium decreases clinical activity and stops progression in patients with mild GO.

Clinical Features of Graves' Ophthalmopathy and Impact of Enalapril on the Course of Mild Graves' Ophthalmopathy: A Pilot Study.

Inflammation, oxidative stress, and adipogenesis are associated with Graves' ophthalmopathy (GO) progression. We conducted a pilot study to investigate the effect of Enalapril on patients with mild ophthalmopathy. Based on the comprehensive eye examination, 12 patients with mild ophthalmopathy were selected from referred Graves' patients and treated with Enalapril (5 mg daily) for 6 months. Clinical and ophthalmological examination [IOP (Intraocular Pressure), vision, Margin reflex distance and exophthalmia measurement, CAS (clinical activity score) and VISA [V (vision); I (inflammation/ congestion); S (strabismus/motility restriction); and A (appearance/exposure] score assessment) was performed at the beginning, 3 months and 6 months of the study period. Quality of life was also evaluated using a standard questionnaire. Mean exophthalmia at the first visit was 18.75 ± 2.39, 3 months later 18.53 ± 2.39 and 6 months later was 17.92 ± 2.31, respectively. Mean CAS was 0.71 ± 0.82 (first visit), 0.57 ± 0.54 (3 months) and 0.14 ± 0.36 (6 months), respectively. Mean Margin reflex distance was 9.09 ± 4.36 (first visit) and 9.60 ± 4.40 (6 months), respectively. There were significant differences in the case of exophthalmia (P=0.002), CAS (P=0.006), and Margin reflex distance (P=0.029) between the first visit and 6 months after treatment. The difference between the score of quality of life in patients with GO after 6 months of follow up was statistically significant (P = 0.006). Our results showed that Enalapril treatment could ameliorate the clinical course of GO according to the ophthalmologic examinations and subjective parameters of disease progression. However, further studies should be performed to determine the efficacy of Enalapril in Graves' ophthalmopathy treatment.

Natural Course of Mild Graves Orbitopathy: Increase of Orbital Fat But Decrease of Muscle Volume With Increased Muscle Fatty Degeneration During a 4-Year Follow-Up.

To describe the natural course of orbital fat volume and extraocular muscle volume in mild Graves orbitopathy during a 4-year follow-up. To describe fatty changes within the extraocular muscles. Twenty-five patients with mild Graves orbitopathy, who did not require any therapeutic intervention other than supportive therapy, were followed for 4 years. CT scans were performed in all patients at baseline and follow-up. A validated technique using Mimics (Materialise) was used to calculate fat and muscle volumes. Outcomes were compared with previously collected data. The amount of intramuscular fat was assessed on CT scans in a semi-quantitative way by two blinded observers according to a four-point scale. After a median follow-up of 4.3 years, the median fat to orbital volume ratio increased with 0.08 from 0.57 to 0.65 (p = 0.000), whereas the median muscle volume to orbital volume ratio decreased with 0.03 from 0.17 to 0.14 (p = 0.000). In this control group in patients between 49 and 54 years old, the changes were 0.01 and -0.002, respectively. The Clinical Activity Score decreased to zero (p = 0.000), and the median eyelid aperture decreased from 12 to 10 mm (p = 0.007). A significant increase of intramuscular fat was found in patients with Graves orbitopathy. The natural course of mild Graves orbitopathy, as observed over 4 years, is characterized by an increase of orbital fat volume, a decrease in muscle volume, and an increased intramuscular fatty degeneration.

SAT-592 Amiodarone-Induced Cure Of Graves' Disease

INTRODUCTION While amiodarone-induced thyrotoxicosis is known to potentially exacerbate latent subclinical hyperthyroidism, we describe a rare case of amiodarone-induced hypothyroidism in a patient with longstanding subclinical hyperthyroidism secondary to Graves disease. CASE The patient is a 66-year-old woman with longstanding subclinical hyperthyroidism due to Graves’ disease and non-toxic multi-nodular goiter. Her mild Graves’ disease was diagnosed nine years back when she presented with hyperthyroidism, negative thyrotropin receptor antibodies (TRAb), and homogenously increased radioactive iodine uptake. The thyroid sonogram and RAI scan had shown bilateral nontoxic nodules, with benign fine needle aspiration cytology. She was intermittently and successfully treated with methimazole 2.5 mg daily, and had no interest in receiving Radioactive Iodine therapy. Her course over the subsequent years was significant for diagnosis of breast cancer treated with lumpectomy and paclitaxel-adriamycin, complicated by the onset of severe congestive heart failure and permanent atrial fibrillation, for which she was started on oral Amiodarone 200mg twice a day. Her serum TSH subsequently increased from baseline 4.53 mcIU/mL (normal 0.73-4.60 mcIU/mL) to 6.04 mIU/L at 6 weeks. Amiodarone dose was tapered to a daily dose and later discontinued because of a prolonged QT on electrocardiogram. Repeat thyroid testing at six months showed a markedly elevated TSH at 66.32 mcIU/mL (normal 0.73-4.60 mcIU/mL) with a serum T4 of less than 0.25 ng/dl (normal 0.58-1.64 ng/dl). TRAb and thyroid peroxidase antibodies remained negative. So with a provisional diagnosis of amiodarone-induced hypothyroidism, methimazole was discontinued and levothyroxine 25 mcg daily started. A follow-up testing one month later showed a TSH of 11.5 mcIU/mL and serum T4 of 0.72 ng/dl. DISCUSSION Amiodarone, through its high iodine content, has been associated with hypothyroidism as well as hyperthyroidism in both normal and dysfunctional thyroid glands. It typically induces thyrotoxicosis in autonomously functioning thyroid glands by stimulating excessive thyroid hormone biosynthesis in response to iodine load, whereas it typically induces hypothyroidism in patients with underlying autoimmune thyroiditis likely because of failure to escape Wolf-Chaikoff effect. Our patient illustrates a very rare and interesting permanent cure of Graves’ disease followed by hypothyroidism after amiodarone exposure.

Selenium and Selenoproteins in Immune Mediated Thyroid Disorders.

Selenium is an essential micronutrient that is required for the synthesis of selenocysteine-containing selenoproteins, processing a wide range of health effects. It is known that the thyroid is one of the tissues that contain more selenium. The “selenostasis” maintenance seems to contribute to the prevention of immune mediated thyroid disorders. Prospective, observational studies, randomized, controlled studies evaluating selenium supplementation, and review articles that are available in Medline and PubMed have undergone scrutiny. The differences concerning methodology and results variability have been analyzed. Several authors support the idea of a potential efficacy of selenium (mainly selenomethionine) supplementation in reducing antithyroperoxidase antibody levels and improve thyroid ultrasound features. In mild Graves’ orbitopathy, selenium supplementation has been associated with a decrease of the activity, as well as with quality of life improvement. Future research is necessary to clearly understand the selenium supplementation biologic effects while considering the basal selenium levels/biomarkers, selenoprotein gene polymorphisms that may be involved, underlying comorbidities and the major clinical outcomes.

Mechanistic Pathways of Selenium in the Treatment of Graves' Disease and Graves' Orbitopathy.

Based on the role of oxidative stress in the pathogenesis of Graves' hyperthyroidism and Graves' orbitopathy, the use of the antioxidant agent selenium has been proposed and several studies on the subject have been conducted, both in vitro and in vivo. Whereas a true benefit related to the use of selenium in patients with Graves' hyperthyroidism has been questioned, its use in patients with mild Graves' orbitopathy is generally believed to be beneficial because of which selenium has entered in the clinical practice for this eye condition.

Selenium in Graves Hyperthyroidism and Orbitopathy.

To review the in vitro and in vivo studies supporting a role of selenium for the treatment of mild Graves orbitopathy. Review of the current literature on the role of selenium in the management of Graves orbitopathy. Graves orbitopathy (GO) is a disfiguring and disabling disorder usually observed in patients with Graves hyperthyroidism, and more rarely in patients with hypothyroid autoimmune thyroiditis or in the absence of overt thyroid dysfunction. Noninvasive treatments include intravenous glucocorticoids and orbital radiotherapy and are generally offered to patients with moderately severe GO. In contrast, patients with mild GO are generally treated only with local measures. Thus, the benefits of intravenous glucocorticoids in mild GO are limited and do not justify the risks that the treatment carries. However, a medical treatment for mild GO is heavily wanted, as a relevant proportion of patients have a significant decrease in their quality of life, and GO can progress into more severe forms. Because of the role of oxidative stress in the pathogenesis of GO, an antioxidant approach has been proposed and the antioxidant agent selenium has been shown to be effective for GO. Studies have shown that a 6-month course of sodium selenite can improve the course of mild GO and prevent deterioration when compared with placebo.

Selenoproteins in human body: focus on thyroid pathophysiology.

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Liečba selénom u tyreopatií

Selenium (latin Selenium) is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet and geographic area. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones. The literature suggests that selenium supplementation of patients with Hashimotos thyroiditis is associated with a reduction in antithyroperoxidase antibody levels. Selenium supplementation also in mild Graves orbitopathy is associated with delayed progression of ocular disorders. As a consequence of this observation The European Group on Graves Orbitopathy recommend six months selenium preparates supportive therapy for patients with mild form of Graves orbitopathy.Key words: Graves-Basedows disease - Hashimotos thyroiditis - selenium - supplementation.

Is selenium supplementation in autoimmune thyroid diseases justified?

This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves' disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves' orbitopathy. The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves' disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.