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Selenium Deficiency

Selenium deficiency occurs due to an insufficient dietary intake of selenium. Because this micronutrient is the essential factor of glutathione peroxidase synthesis and is involved in various metabolic processes, it may predispose individuals to various diseases. Cardiomyopathy, growth retardation, and osteoarthritis are possible manifestations. The diagnosis is made clinically and indirectly by measuring glutathione peroxidase in blood, while treatment includes supplementation.


Presentation

Depending on the organ systems involved, selenium deficiency may manifest with various symptoms. Early manifestations include growth retardation, alopecia and cognitive changes [14], while cardiac abnormalities are seen in patients who develop Keshan disease. Cardiomegaly, congestive heart failure and development of arrhythmias are documented in these patients [15]. On the other hand, Kashin-Beck disease includes symptoms such as bone and joint pain as a result of chronic osteoarthritis. Other symptoms that may be observed include myalgia, generalized weakness, and fatigue.

Intravenous Administration
  • After intravenous administration of sodium selenite, her symptoms were reversed.[ncbi.nlm.nih.gov]
Noncompliance
  • The purpose of the run-in visits was to identify for potential exclusion individuals who were noncompliant or who were no longer interested or study eligible. Ways to overcome obstacles to supplement adherence were discussed.[archinte.ama-assn.org]
Chest Pain
  • A 42-year-old white man with Crohn's disease who was receiving HPN was admitted to the hospital with severe chest pain and dyspnea.[ncbi.nlm.nih.gov]

Workup

Because symptoms of selenium deficiency are not specific, other modalities can be helpful in excluding this diagnosis as a possible cause. Patient history, including the duration of illness and dietary habits, may be particularly useful.

In terms of laboratory workup, indirect values of serum selenium may be obtained through measuring glutathione peroxidase in plasma, but this test is not commercially available. Determination of selenium in plasma is a test that could confirm the diagnosis, but it is not available in regular medical practice as well [16]. The diagnosis remains on clinical grounds, while evaluation of thyroid hormones, levels of pancreatic enzymes and creatine kinase (CK) may be useful in assessing organs that may be affected.

Staphylococcus Aureus
  • Bacterial killing of Staphylococcus aureus 502A and cardiac function were not affected by selenium deficiency. Thus, selenium deficiency resulted in biochemical and functional abnormalities of erythrocytes and granulocytes.[ncbi.nlm.nih.gov]
Ventricular Hypertrophy
  • Histological examination evidenced dilated cardiomyopathy in 45% of cases, left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%.[ncbi.nlm.nih.gov]

Treatment

The mainstay of the treatment of patients with selenium deficiency is supplementation with sodium selenite, in doses of 100 µg/day, taken as oral tablets. Once initial supplementation restores selenium values, food sources should be the primary source of this micronutrient. Brazil nuts contain by far the highest amount of selenium (544 µg per serving) while tuna, sardines, eggs, beef, chicken, cottage cheese and other similar products can be sufficient dietary sources [17].

Prognosis

Symptoms that occur in infants and adults with selenium deficiency can be corrected with adequate supplementation, but this condition may cause significant consequences. Growth retardation, cardiomyopathy, and hypothyroidism may present significant morbidity to patients, which is why adequate supplement therapy should be conducted.

Etiology

The universal cause of selenium deficiency is insufficient intake through diet. The recommended daily intake of selenium differs from country to country, but it approximately ranges from 45-75 µg/day in Europe, while the United States have somewhat higher recommended values.

Epidemiology

Selenium deficiency is strictly related to its intake through nutrition. In some regions of the world, like China, where dietary intake is significantly below the recommended values (< 20µg/day), more frequent reports of Keshan and Kashin-Beck diseases are seen. Additionally, patients who are on long-term total parenteral nutrition are at increased risk for developing selenium deficiency, but also is the same for patients on hemodialysis [5], and those with HIV infection [6].

This condition is seen both in children and adults, but more pronounced symptoms related to bone and muscle growth may be observed in children.

Sex distribution
Age distribution

Pathophysiology

Selenium is an important cofactor of various metabolic functions and is an essential component of selenoproteins. So far, numerous selenoproteins have been identified and they are primarily involved in oxidoreductive reactions that regulate free-radical mediated damage. However, thyroid hormone synthesis, sperm maturation, muscular function and numerous other roles of these proteins have been established, making them extremely important for the human organism [7].

The most important recognized function of selenium is its cofactor role in the formation of glutathione peroxidases, one of the most important groups of enzymes responsible for a conversion of free radicals into harmless substances. In the case of selenium deficiency, a decreased activity of this enzyme has been observed, which can lead to a significantly impaired ability of the organism to regulate the activity of reactive oxygen species (ROS). As a result, ROS can cause tissue damage, suppress normal immune function and induce rapid mutations in viral genetic material, which has led to the finding that coxsackie virus is implicated in the pathogenesis of Keshan disease. Other viral pathogens as well, including HIV, influenza virus, severe acute respiratory syndrome (SARS) coronavirus and possibly Ebola virus [8], have been brought into connection with selenium deficiency. It is established that selenium is an important factor in maintaining normal innate immune responses, including activation of IL-2 and NK cell function [9], which are one of the main barriers for viral pathogens.

In addition to research which suggests that selenium deficiency may predispose individuals to certain infections, hypothyroidism due to iodine deficiency and chronic pancreatitis are also conditions in which selenium may play a role. In the setting of iodine deficiency, increased production of hydrogen peroxide occurs as a result of thyroid-stimulating hormone (TSH) activation. In turn, insufficient levels of selenium reduce the capacity for reduction of oxidative stress, leading to cellular damage and impaired thyroid function [10]. The identical mechanism is postulated in chronic pancreatitis, where free radical injury leads to severe damage of the parenchyma.

Kashin-Beck disease is a condition characterized by chronic osteoarthritis in several regions of China in which selenium deficiency was reported as well, which brings into connection the two clinical syndromes [11].

The same mechanism is hypothesized to contribute to a development of cancer. Namely, oxidative stress is known to be a part of the pathogenesis of malignant tumors and low selenium concentrations have shown significant correlations with a prevalence of cancer in some studies. However, results have been conflicting, while very large studies have indicated that the connection between the two entities is yet to be determined [12].

Selenium deficiency has also been investigated in patients with extensive burns, as extensive free-radical damage occurs in this type of injury [13].

Prevention

Complete eradication of symptoms and illnesses in which selenium deficiency is reported to be the primary cause can be achieved through preventive supplementation. In individuals in whom dietary intake of selenium is not sufficient, preventive administration of sodium selenite (around 50 µg/day) may effectively prevent the development of cardiomyopathies, growth abnormalities and osteoarthritis that are seen in these patients. Several food industries are enriching crops with selenium so that adequate daily intake can be achieved, and are proving to be effective in some parts of the world.

Summary

Selenium deficiency is a nutritional disease and occurs exclusively because of insufficient intake of selenium through diet. This micronutrient is an essential component of several metabolic pathways [1]. Certain patient groups, such as those on total parenteral nutrition (TPN), hemodialysis and those with human immunodeficiency virus (HIV) infection have been established to be at greater risk for this disorder. Selenium deficiency is considered endemic in certain parts of the world, such as parts of China, Russia and other countries in which adequate daily intake through food is not achieved. Among various functions that selenium performs in the human body, the most important one is its role in synthesis and function of glutathione peroxidase (GPx), one of the main enzymes involved in controlling free-radical injury [2]. In selenium deficiency, this enzyme is not synthesized in the necessary amount and is consequently not able to sustain levels of free radicals that are produced during metabolic processes, ultimately leading to cellular damage. Selenium has also been established to be an important constituent of the immune response. Apart from GPx, selenium has established roles in muscle function, synthesis of thyroid hormones and possibly an arising of malignant tumors through free-radical mediated DNA damage as a result of GPx inactivity [3]. Keshan disease, manifested by cardiomyopathy, and Kashin-Beck disease, characterized by significant growth retardation and chronic osteoarthritis, are supposed consequences of selenium deficiency.

Hypothyroidism, as a result of a necessity of selenium involvement in a production of T4 and T3 [4], as well as chronic pancreatitis, have also been correlated with selenium deficiency. The diagnosis can be made by measurement of GPx in serum and obtain an indirect view of selenium levels, but this test is not readily available in clinical practice, nor is direct selenium evaluation in serum, which could confirm the diagnosis. Treatment includes supplementation by sodium selenite in doses of 100 µg/day, while adequate nutritional changes should be performed to establish recommended the daily intake, which ranges between 45-75 µg/day. Preventive strategies, through prophylactic supplementation of populations at risk with sodium selenite, may effectively reduce the burden of this condition. One of the strategies that some countries have used is soil enrichment with selenium, to ensure adequate dietary intake through food. By far, the highest amount of selenium can be found in Brazil nuts, but various fish, meat, eggs and rice are also good sources of this micronutrient.

Patient Information

Selenium is an element used by the body in various important metabolic functions and is necessary for battling free radicals. Recommended daily intake of selenium varies across different parts of the world but is generally around 50 µg/day. Selenium deficiency occurs when dietary intake through food does not meet the metabolic demands. Certain parts of the world are considered to be endemic for this condition, such as parts of China and Russia, in which food does not have adequate concentrations of this element. Because of selenium deficiency, various functions in the body are impaired, most notably the ability to reduce free-radical damage, while certain parts of the immune system may not be as effective. Keshan disease, which is a form of selenium deficiency, is characterized by heart damage and development of cardiomyopathy and arrhythmias. Presumably, it occurs due to viral infection by Coxsackie virus and inability of the immune system to fight against it as a result of disrupted functions in which selenium is an essential component. Kashin-Beck is another form of selenium deficiency characterized by growth retardation and chronic bone and joint pain. In some cases, hypothyroidism may be triggered, because selenium is involved in the synthesis of thyroid hormones, with symptoms such as fatigue, blood pressure and weight changes, as well as cognitive decline. The diagnosis is made clinically because a direct evaluation of selenium in blood is rarely available. The treatment includes supplementation with sodium selenite tablets. Prevention of this disorder can be made by continuous supplementation, while adequate nutrition changes should be implemented. Brazil nuts contain by far the highest amount of selenium, followed by various types of fish, including tuna and sardines, then meat such as beef and chicken, while dairy products can also be a sufficient source of selenium.

References

Article

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  4. Rayman MP. Dietary selenium: time to act. BMJ. 1997;314(7078):387-388.
  5. Tonelli M, Wiebe N, Hemmelgarn B, et al. Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Medicine. 2009;7:25.
  6. Baum MK, Shor-Posner G, Lai S, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;15:370-374.
  7. Rederstorff M, Krol A, Lescure A. Understanding the importance of selenium and selenoproteins in muscle function. Cell Mol Life Sci. 2006;63(1):52-59.
  8. Harthill M. Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res. 2011;143(3):1325-1336.
  9. Ravaglia G, Forti P, Maioli F, et al. Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged ≥90 years. Am J Clin Nutr. 2000;71(2):590-598.
  10. Duntas LH. Selenium and the thyroid: a close-knit connection. J Clin Endocrinol Metab. 2010;95(12):5180-5188.
  11. Peng A, Yang C, Rui H, et al; Study on the pathogenic factors of Kashin-Beck disease. J Toxicol Environ Health. 1992;35(2):79-90.
  12. Vinceti M, Dennert G, Crespi CM, et al. Selenium for preventing cancer. Cochrane Database Syst Rev. 2014;3:CD005195.
  13. Berger MM. Antioxidant micronutrients in major trauma and burns: evidence and practice. Nutr Clin Pract. 2006;21(5):438-449.
  14. Masumoto K, Nagata K, Higashi M, et al. Clinical features of selenium deficiency in infants receiving long-term nutritional support. Nutrition. 2007;23(11-12):782-787.
  15. Chen J. An original discovery: selenium deficiency and Keshan disease (an endemic heart disease). Asia Pac J Clin Nutr 2012;21:320-326.
  16. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J. 2011;
  17. U.S. Department of Agriculture, Agricultural Research Service. USDA National Nutrient Database for Standard Reference, Release 25. U.S. Department of Agriculture. 2012;

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Last updated: 2019-07-11 21:15