All rights reserved. Mayo Clinic on Incontinence - Mayo Clinic Press, NEW The Essential Diabetes Book - Mayo Clinic Press, NEW Ending the Opioid Crisis - Mayo Clinic Press, FREE Mayo Clinic Diet Assessment - Mayo Clinic Press, Mayo Clinic Health Letter - FREE book - Mayo Clinic Press. Hypothyroidism, or an underactive thyroid, is a common problem. T4 and T3 circulate almost entirely bound to specific transport proteins. Background: To investigate whether high thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels are associated with increased risk of lymph node metastasis (LNM) of thyroid cancer. Most of these patients will have recovery of euthyroidism, but some may benefit from treatment aimed at relieving symptoms of hyperthyroidism or hypothyroidism, provided they are monitored for anticipated changes in thyroid function. The timing likely reflects a rebound in immune function after a period of relative immune tolerance during pregnancy. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed TSH, and low uptake of iodine 123 on thyroid scanning. When the heat rises to an appropriate level, the thermostat senses this and turns off the heater. It is used most often in patients who have had surgery for thyroid cancer in order to monitor them after treatment. Antibodies can be high, even though you have no symptoms and/or thyroid test levels are in the normal range. Results: About 95% of people with Hashimoto's have elevated Thyroid Peroxidase Antibodies, while 80% will have elevated Thyroglobulin Antibodies. This site needs JavaScript to work properly. Recurrence; Thyroglobulin; Thyroglobulin antibody; Thyroid cancer; Total thyroidectomy. Patients with severe thyroid pain and systemic symptoms (e.g., high fever, leukocytosis, cervical lymphadenopathy) should undergo fine-needle aspiration to rule out infectious thyroiditis.26. This occurs mainly in the liver and in certain tissues where T3 acts, such as in the brain. 6 7 Thyroid Peroxidase Antibodies (TPO) Optimal range: 0 -9 IU/mL Thyroid peroxidase is an enzyme used in the synthesis of thyroid hormone. Keywords: Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. Objective: The study aimed to assess antithyroid antibodies in patients with benign thyroid masses and the effect of total thyroidectomy on the antibodies titers. As the devastating outbreak of Covid-19 spread in Italy in March, doctors became curious if the ruthless virus, which seemed to wreak unpredictable havoc on the body, was mucking with important organs like the thyroid. We live in a rural area of Arizona and the doctors don't seem to understand Autoimmune issues. If the patient presents beyond the thyrotoxic phase, which typically lasts four to eight weeks, TSH and free T4 levels may be low. Do you have high TPO or high TPOab? This was not addressed by the doctor at the time and when he recently ran the T3, T4 and TSH he also accidentally ordered a TPO test. An official website of the United States government. . Thyroid peroxidase is an enzyme which helps to make thyroid hormones ( T3, T4 and TSH ). But the presence of TPO antibodies may increase the risk of future thyroid disorders. The .gov means its official. Thyroid peroxidase (TPO) Antibodies. Log-Rank analysis could not determine a relationship between TgAb status and recurrent cancer. All Rights Reserved. It is an autoimmune disease. Antibodies that attack the thyroid gland cause swelling, rarely tenderness and reduced function of the thyroid. Accessed Aug. 5, 2020. In the case of postpartum, silent, or subacute thyroiditis, the radioactive iodine uptake during the hyperthyroid phase will be low. I had a total thyroidectomy and RAI 131 for thyroid cancer. Very high TPO more common with autoimmune thyroiditis (Hashimoto's) To confirm suspicion of hyper Graves. J Surg Res. The https:// ensures that you are connecting to the Patients recovering from recent illness or those taking drugs such as glucocorticoids or opiates may have suppressed TSH, but free thyroid hormone levels will be normal or low. Patients may present in the hypothyroid or hyper-thyroid phase. The family physician will most commonly diagnose thyroiditis because of abnormal results on thyroid function testing in a patient with symptoms of thyroid dysfunction or anterior neck pain. If the levels of these transport proteins changes, there can be changes in how much bound T4 and T3 is measured. Thyroid tests. FREE T3 In one study of 121 children with vitiligo, 16% showed some abnormalities in the thyroid function tests, The antithyroid peroxidase antibody (Anti-tpo) was the most common disorder. Table 1 summarizes key aspects of thyroiditis, including less common forms. Accessibility Thyroid stimulating immunoglobulin or TSI for short (1) is the name of a blood test that is used to identify the presence of autoimmune disease in those with hyperthyroidism. 2018 Jan;163(1):118-123. doi: 10.1016/j.surg.2017.05.028. A Total T4 measures the bound and free hormone and can change when binding proteins differ (see above). I did get the antibodies checked in the full blood test but they seem to really low so I think I'm fine on that front. Hypothyroidism is a condition in which the thyroid . There are few large epidemiologic studies on subacute thyroiditis; however, one large community-based study performed in Olmstead County, Minn., between 1960 and 1997 reported an incidence of 4.9 cases per 100,000 persons per year.20 Women are significantly more likely to be affected than men, and the peak incidence in both sexes occurs at 40 to 50 years of age.20,21 Cases of subacute thyroiditis generally cluster in the late summer and fall.20,21 An increased association of subacute thyroiditis in persons with HLA-B35 is well established.2224. FNA with Tg washout - the Tg in the residual of the syringe was 7339. 174 views Reviewed >2 years ago. The most specific autoantibody test for autoimmune thyroiditis is an enzyme-linked immunosorbent assay (ELISA) test for anti thyroid peroxidase (anti-TPO) antibody. The follow-up of patients with differentiated thyroid cancer and undetectable thyroglobulin (Tg) and Tg antibodies during ablation. Increased sweating. Unexplained weight loss. There are many medications that can affect thyroid function testing. The TSH of 0.29 is actually not a bad place to be in the first 5 years after Thyroidectomy. It makes hormones that control the way the body uses energy. Disease Free Survival based on TgAb status. 2008 Jan;158(1):77-83. doi: 10.1530/EJE-07-0399. Log-Rank analysis showed. A single copy of these materials may be reprinted for noncommercial personal use only. TPO is an enzyme used to produce thyroid hormones, TPOab is antibodies that attack and destroy healthy thyroid tissue. Persistently elevated levels after thyroidectomy were not associated with disease recurrence in our series. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. This frequently happens during pregnancy and with the use of birth control pills. Table 2 summarizes drugs associated with thyroiditis.18, Figure 1 is an algorithm for the diagnosis of thyroiditis.9, Presence of nontender goiter; thyroid function tests; elevated TPO antibody levels, Presence of an elevated TPO antibody level confers risk for many types of thyroid dysfunction and is a general marker of thyroid autoimmunity; a frankly elevated TPO antibody level is more specific for Hashimoto thyroiditis, In type 1 amiodarone-induced thyrotoxicosis there is increased synthesis of thyroid hormone (usually in patients with preexisting goiter), In type 2 amiodarone-induced thyrotoxicosis there is excess release of thyroxine and triiodothyronine into the circulation caused by destructive thyroiditis, Type 1 is treated with antithyroid medications (thioureas) and type 2 is treated with glucocorticoids; in both cases, beta blockers can be used for symptoms of hyperthyroidism1,2. Thyroid peroxidase antibody test: What is it? TPO signifies thyroid autoimmune in both under active and over active thyroid diseases. What in the world could be going on? It can, however, present without a goiter (atrophic form). STIs are the most common cause of genital sores. In this narrative review, the major results and limitations of the . Treatment requires taking thyroid hormone pills. Advertising revenue supports our not-for-profit mission. Zelaya AS, Stotts A, Nader S, Moreno CA. Surveillance and clinical follow-up are necessary in all forms of thyroiditis because of the potential for change in thyroid status. In: Laposata's Laboratory Medicine: Diagnosis of Disease in the Clinical Laboratory. Unlike thyroglobulin antibodies, TPO antibodies can stimulate the immune system and cause inflammation in thyroid tissue, leading to the development of thyroid disease [ 2 ]. High thyroid antibodies can also cause an imbalance in hormone production which can . Phan HT, Jager PL, van der Wal JE, Sluiter WJ, Plukker JT, Dierckx RA, Wolffenbuttel BH, Links TP. If you've been diagnosed with thyroid disease, your doctor may suggest a TPO antibody test and other thyroid . A list of national and international resources and hotlines to help connect you to needed health and medical services. Patients with subacute thyroiditis should be started on high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs as first-line therapy. Permanent hypothyroidism is uncommon but is reported to develop in up to 15% of patients with subacute thyroiditis, and can develop more than one year following presentation.20 It should be noted that the use of corticosteroids is not associated with a lower incidence of permanent hypothyroidism.20 Rarely, patients may experience recurrent episodes of subacute thyroiditis. Log-Rank analysis could not determine a, MeSH Your doctor may also order a TPO antibody test if you are pregnant and have an autoimmune disease that involves the thyroid, such as Hashimoto's disease or Graves' disease. To avoid unnecessary surgery, PET/CT scan is a possible alternative to help differentiate between benign and malignant ITN. If you've been diagnosed with thyroid disease, your doctor may suggest a TPO antibody test and other thyroid tests to help find the cause. Sign up for free, and stay up to date on research advancements, health tips and current health topics, like COVID-19, plus expertise on managing health. A publication of the American Thyroid Association, Summaries for the Public from recent articles in Clinical Thyroidology, Table of Contents | PDF File for Saving and Printing, HYPOTHYROIDISM Two common antibodies are thyroid peroxidase antibody and thyroglobulin antibody. Dosages of 25 to 50 mcg per day of levothyroxine can be initiated in these patients and titrated to the same TSH goals as in overt hypothyroidism. Hypothyroidism (Underactive): https://www.thyroid.org/hypothyroidism/, Hashimotos Thyroiditis: https://www.thyroid.org/hashimotos-thyroiditis/, Thyroid Surgery: https://www.thyroid.org/thyroid-surgery/, Thyroid Hormone Treatment: https://www.thyroid.org/thyroid-hormone-treatment/. Guldvog I et al Thyroidectomy versus medical management of euthyroid patients with Hashimotos Disease and Persistent Symptoms: a randomized trial. Key points about Hashimoto's thyroiditis. Indeterminate thyroid nodules (ITN) are commonly encountered among the general population, with a malignancy rate of 10 to 40%. I had TT in January 2009, and in November 2016 my Tg level was suddenly detectable after being undetectable for years. They all had a TPOAb titer >1000 IU/L and reported persistent symptoms despite having normal thyroid hormone levels based on blood tests. Hypothyroidism: a condition where the thyroid gland is underactive and doesnt produce enough thyroid hormone. Please enable it to take advantage of the complete set of features! In autoimmune disorders, your immune system makes antibodies that mistakenly attack normal tissue. High-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs are usually the first-line treatment.25 There are no randomized controlled trials comparing doses or agents. I am frightened. The thyroid gland is a butterfly-shaped endocrine gland that is normally located in the lower front of the neck. Thus, the thyroid and the pituitary, like a heater and thermostat, turn on and off. The thyroid has developed a very active mechanism for doing this. TESTS: - High serum thyroid peroxidase antibody concentrations are present in 90% of these patients. I received my comprehensive thyroid panel test today but dont know how to read it. The McGraw-Hill Companies; 2019. https://accessmedicine.mhmedical.com. Thyroid function tests. The differential diagnosis between benign and malignant thyroid disorders and the potential identification of thyroid microcarcinomas with biochemical markers remain controversial. It is not a measure of thyroid function and it does not diagnose thyroid cancer when the thyroid gland is still present. The purpose of the study was to assess the long-term outcome of DTC patients with raised TgAb. Our purpose was to describe the TgAb resolution time course and the significance of persistent antibody elevation after thyroidectomy. Thyroid gland physiology and testing. Matrone A, Latrofa F, Torregrossa L, Piaggi P, Gambale C, Faranda A, Ricci D, Agate L, Molinaro E, Basolo F, Vitti P, Elisei R. Thyroid. Following antibody levels in Graves patients may help to assess response to treatment of hyperthyroidism, to determine when it is appropriate to discontinue antithyroid medication, and to assess the risk of passing antibodies to the fetus during pregnancy. Treatments can help. Practice Essentials. Measurement of free T3 is possible, but is often not reliable and therefore not typically helpful. Antibodies (TPOab) can be present if other autoimmune diseases are there too. 1.50 - 38.5 ng/mL for women. . In countries where iodine deficiency is common (not the US), the reference range may be higher [ 5, 6, 7 ]. . sured by elevated thyroid peroxidase antibody (TPO Ab).6,7 To date, there is no algorithm for treatment in these refractory cases. TPO converts iodide ions absorbed from food into an active form of iodine to be used by the body. The radioactivity allows the doctor to track where the iodine goes. Thyroid antibodies explained . A family or personal history of autoimmune thyroid disease confers increased risk, and there is a strong female predominance in this disorder. Elevated thyroid peroxidase antibodies. These non-self proteins are called antigens. This is an autoimmune disorder where antibodies attack the thyroid, causing inflammation and destruction of the gland. In autoimmune forms of thyroid diseaseespecially Hashimoto disease and Graves' diseaseantibodies may be formed to thyroid peroxidase. TPO antibodies will be present in 90% of affected persons. Also, patients had quite high levels of the TPO Antibody which may not be the case in all patients with Hashimotos thyroiditis. Although most women with postpartum thyroiditis will become euthyroid, treatment with levothyroxine should be considered in women with a serum TSH level greater than 10 mIU per L, or in women with a TSH level of 4 to 10 mIU per L who are symptomatic or desire fertility. Postpartum hyperthyroidism and Graves disease are characterized by elevated free thyroid hormones and suppressed TSH; however, postpartum thyroiditis has a lower free T3 to free T4 ratio, because free T4 is the predominant form of thyroid hormone produced by the thyroid gland, and thereby is released into the bloodstream secondary to glandular inflammation and destruction. Chronic autoimmune thyroiditis (Hashimoto thyroiditis, chronic lymphocytic thyroiditis), Hypothyroidism; rarely thyrotoxicosis secondary to alternating stimulating and inhibiting thyroid autoantibodies, Infectious thyroiditis (suppurative thyroiditis), Thyroid pain, high fever, leukocytosis, and cervical lymphadenopathy; focal inflammation may result in compressive symptoms such as dysphonia or dysphagia; patients may assume a posture to limit neck extension; palpation may reveal focal or diffuse swelling of the thyroid gland and the overlying skin will be warm and erythematous; presence of fluctuance suggests abscess formation, Multiple infectious organisms, most commonly bacterial, Thyroid fine-needle aspiration with Gram stain and culture; blood cultures; neck magnetic resonance imaging or computed tomography with contrast media; plain radiography of the lateral neck may reveal gas in the soft tissues; thyroid autoantibodies are generally absent; serum thyroxine and triiodothyronine levels are usually normal, Acute complications may include septicemia and acute airway obstruction; later sequelae of the acute infection may include transient hypothyroidism or vocal cord paralysis, Hospitalization and treatment with intravenous antibiotics (nafcillin plus gentamicin or a third-generation cephalosporin); abscess formation may necessitate surgical drainage; euthyroidism is generally restored after treatment of infection, Hyperthyroidism alone; hyperthyroidism followed by hypothyroidism; or hypothyroidism alone within one year of parturition, Thyroid function tests; elevated TPO antibody levels; low radioactive iodine uptake in the hyperthyroid phase, Euthyroidism is generally achieved by 18 months, but up to 25% of women become permanently hypothyroid; high rate of recurrence with subsequent pregnancies, Beta blockers can be considered for significant hyperthyroid symptoms (in the hyperthyroid phase); levothyroxine for symptomatic hypothyroidism (in the hypothyroid phase) and for permanent hypothyroidism, Patients may present with thyroid pain and transient thyrotoxicosis, Clinical diagnosis made in the setting of recent previous radiation, Hyperthyroidism generally resolves within one month, Self-limited, but symptoms may be treated with beta blockers and nonsteroidal anti-inflammatory drugs, Very firm goiter or compressive symptoms (dyspnea, stridor, dysphagia), which appear disproportionate to the size of the thyroid; hypocalcemia may occur as a result of fibrotic transformation of the parathyroid glands, Autoimmunity may contribute to the pathogenesis, Most patients are euthyroid, approximately 30% are hypothyroid, Glucocorticoids and mycophenolate (Cellcept); tamoxifen may work by inhibiting fibroblast proliferation, Silent thyroiditis (silent sporadic thyroiditis, painless sporadic thyroiditis, subacute lymphocytic thyroiditis), Hyperthyroidism alone; hyperthyroidism followed by hypothyroidism; or hypothyroidism alone, Euthyroidism is generally achieved by 18 months, but up to 11% of patients become permanently hypothyroid; rarely recurs, Beta blockers can be considered for significant hyperthyroid symptoms (in the hyperthyroid phase); levothyroxine for symptomatic hypothyroidism (in the hypothyroid phase) and permanent hypothyroidism, Subacute thyroiditis (subacute granulomatous thyroiditis, giant cell thyroiditis, de Quervain thyroiditis), Thyroid pain; hyperthyroidism followed by transient hypothyroidism most commonly, Euthyroidism is generally achieved by 18 months, but up to 15% of patients become permanently hypothyroid; rarely recurs, Atrial fibrillation, ventricular arrhythmia, Persistent or recurrent cutaneous T cell lymphoma, psoriasis, graft-versus-host disease, chronic lymphocytic leukemia, Hairy cell leukemia, follicular lymphoma, malignant melanoma, AIDS-related Kaposi sarcoma, chronic hepatitis B and C, Hypothyroidism more often than hyperthyroidism, Gastrointestinal stromal tumors, renal cell carcinoma. C 12 Patients can be severely hypothyroid with a high TSH and low FT4 or FTI, but have a normal T3. Diet can be a complementary treatment for Hashimoto's disease by affecting thyroid function and anti-inflammatory properties. Blood tests to measure these hormones are readily available and widely used, but not all are useful in all situations. Tg is included in this brochure of thyroid function tests to communicate that, although measured frequently in certain scenarios and individuals, Tg is not a primary measure of thyroid hormone function. Your thyroid is a small, butterfly-shaped gland in the front of your neck. Subacute thyroiditis is self-limited, and in most cases the thyroid gland spontaneously resumes normal thyroid hormone production after several months. and transmitted securely. Background: Thyroglobulin antibodies (TgAb) are produced by 10%-25% of thyroid cancer patients and interfere with thyroglobulin measurement, a marker of residual or recurrent cancer after surgery. . For example, positive anti-thyroid peroxidase and/or anti-thyroglobulin antibodies in a patient with hypothyroidism result in a diagnosis of Hashimotos thyroiditis. Copyright 2023 American Academy of Family Physicians. There are several natural approaches to balancing your immune system and addressing leaky gut. About 10 percent of patients with chronic autoimmune hypothyroidism have atrophic thyroid glands (rather than goiter), which may represent the final stage of thyroid failure in Hashimoto's thyroiditis. Clinical implications of anti-thyroglobulin antibody measurement before surgery in thyroid cancer. Disease-free survival was equivalent between TgAb-positive and TgAb-negative groups (P = 0.8). The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. In its mildest form, hyperthyroidism may not cause noticeable symptoms; however, in some patients, excess thyroid hormone and the resulting effects on the body can have significant consequences. A database of 247 consecutive patients with TgAb measured preoperatively who underwent thyroidectomy for differentiated thyroid cancer between January 2007 and May 2013 was reviewed. Mayo Clinic; 2020. Many thanks for replying so quickly Stella5349 and Barb135. A high Thyroid Peroxidase Antibody (TPO) level is defined as a level higher than 35 IU/mL, as documented in research conducted by the Mayo Clinic. While detecting antibodies is helpful in the initial diagnosis of hypothyroidism due to autoimmune thyroiditis, following their levels over time is not helpful in detecting the . HHS Vulnerability Disclosure, Help Thyroglobulin antibody resolution after total thyroidectomy for cancer. Methods: This is a database study of all patients undergoing thyroidectomy with recorded preoperative thyroid antibodies (autoantibodies to thyroglobulin and/or thyroid peroxidase) levels from 2010 to 2012. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Other signs of thyrotoxicosis such as fever, tachycardia, tremor, and increased skin warmth may be present. If your thyroid peroxidase antibodies fall within the 0 to 34 range they will be considered "normal" and they won't flag as high on your lab tests. the unsubscribe link in the e-mail. A low TSH with an elevated FT4 or FTI is found in individuals who have hyperthyroidism. Elevated levels may also indicate a high risk of thyroid cancer recurrence after treatment [ 4. Before These antibodies can be a sign of: Hashimoto disease, also known as Hashimoto thyroiditis. New research has found a link between serious coronavirus infections and the thyroid. The aim of this systematic review is to examine all the data currently available in the literature on the effects of nutritional intervention on biochemical parameters (anti-thyroid antibody . Thyroid peroxidase antibodies will usually go away if a radical thyroidectomy is done for thyCa but may not if a lot of thyroid tissue remains after thyroidectomy for goitre/nodule removal or hyperthyroidism. This raises the possibility that some symptoms may be related to the autoimmune condition itself. Heat intolerance. TPO antibodies (TPOAb): these are antibodies that attack the thyroid instead of bacteria and viruses, they are a marker for autoimmune thyroid disease, which is the main underlying cause for hypothyroidism and hyperthyroidism in the United States. health information, we will treat all of that information as protected health Clinical aggressiveness and long-term outcome in patients with papillary thyroid cancer and circulating anti-thyroglobulin autoantibodies. RADIOACTIVE IODINE UPTAKE The "normal" reference range for TPO antibodies is less than 35 IU/mL. The range for the TPO test that was run was 0-30 and mine was 303. Patients were stratified by TgAb status (positive or negative) and recurrence (defined as biopsy proven disease or unplanned second surgery). Hi. Epub 2019 Mar 12. MedHelp is not a medical or healthcare provider and your use of this Site does not create a doctor / patient relationship. Bates MF, Lamas MR, Randle RW, Long KL, Pitt SC, Schneider DF, Sippel RS. Patients with elevated thyroid peroxidase antibody levels and subclinical hypothyroidism should be monitored annually for the development of overt hypothyroidism. TPO helps with the conversion of T4 to T3. Often, even when these are "in range", the patient does not feel well. This week, researchers have added another to the listthe thyroid. T3 TESTS Surgery. Regression analysis of patients with antibody resolution yielded an average decline of -11% IU/mL per month 2.2%. Not per se: Antibodies to thyroglobulin are not an issue if you had a thyroidectomy. other information we have about you. . In women, there is a prevalence of post-partum thyroid disease of about 6% occurring around 6 months after delivery. First, the laboratory test result should be confirmed, and free thyroxine (T4) and free triiodothyronine (T3) levels should be measured. Men and women who had chronic widespread musculoskeletal pain (often diagnosed as "fibromyalgia . Feeling shaky 4. The thyroid examination will commonly reveal a firm, bumpy gland with symmetric enlargement. If persistent symptoms in patients with Hashimotos thyroiditis are caused by the active autoimmune process rather than by thyroid hormone status, removing the thyroid gland through surgery may reduce the levels of the TPOAb and improve some symptoms. The finding of an elevated TSH and low FT4 or FTI indicates primary hypothyroidism due to disease in the thyroid gland. Advertising and sponsorship opportunities. By measuring the amount of radioactivity that is taken up by the thyroid gland (radioactive iodine uptake, RAIU), doctors may determine whether the gland is functioning normally. 4. Even in euthyroid women, elevated TPO antibodies (anti-TPO) are strongly associated with a higher prevalence of infertility, gestational anemia, miscarriage and preterm delivery. In the first study, 100 people were recruited to receive nigella or a placebo for 8 weeks. In 9 of 34 patients, antibodies had not resolved at the last follow-up and imaging could not identify recurrent disease. Reading and interpreting thyroid blood tests results can often be a challenge. I have TPO levels in the 300 range, but all other thyroid test levels are mid range normal. The immune system of the body normally protects us from foreign invaders such as bacteria and viruses by destroying these invaders with substances called antibodies produced by blood cells known as lymphocytes.
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