Iodine deficiency

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Iodine deficiency
Specialty Endocrinology

Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.

Contents

Iodine is an essential dietary mineral for neurodevelopment among children. [1] The thyroid hormones thyroxine and triiodothyronine contain iodine. In areas where there is little iodine in the diet, typically remote inland areas where no marine foods are eaten, iodine deficiency is common. It is also common in mountainous regions of the world where food is grown in iodine-poor soil.

Prevention includes adding small amounts of iodine to table salt, a product known as iodized salt . Iodine compounds have also been added to other foodstuffs, such as flour, water and milk, in areas of deficiency. [2] Seafood is also a well known source of iodine. [3]

In the U.S., the use of iodine has decreased over concerns of overdoses since mid-20th century, and the iodine antagonists bromine, perchlorate and fluoride have become more ubiquitous. [4] In particular, around 1980 the practice of using potassium iodate as dough conditioner in bread and baked goods was gradually replaced by the use of other conditioning agents [5] such as bromide.[ citation needed ]

Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). [6] It resulted in 2700 deaths in 2013, up from 2100 deaths in 1990. [7]

Signs and symptoms

Goiter

A low amount of thyroxine (one of the two thyroid hormones) in the blood, due to lack of dietary iodine to make it, gives rise to high levels of thyroid stimulating hormone (TSH), which stimulates the thyroid gland to increase many biochemical processes; the cellular growth and proliferation can result in the characteristic swelling or hyperplasia of the thyroid gland, or goiter. In mild iodine deficiency, levels of triiodothyronine (T3) may be elevated in the presence of low levels of levothyroxine, as the body converts more of the levothyroxine to triiodothyronine as a compensation. Some such patients may have a goiter, without an elevated TSH. The introduction of iodized salt since the early 1900s has eliminated this condition in many affluent countries; however, in Australia, New Zealand, and several European countries, iodine deficiency is a significant public health problem. [8] It is more common in developing countries. Public health initiatives to lower the risk of cardiovascular disease have resulted in lower discretionary salt use at the table. Additionally, there is a trend towards consuming more processed foods in western countries.[ citation needed ] The noniodized salt used in these foods means that people are less likely to obtain iodine from adding salt during cooking.

Goiter is said to be endemic when the prevalence in a population is > 5%, and in most cases goiter can be treated with iodine supplementation. If goiter is untreated for around five years, however, iodine supplementation or thyroxine treatment may not reduce the size of the thyroid gland because the thyroid is permanently damaged.

Congenital iodine deficiency syndrome

Congenital iodine deficiency syndrome, previously known as cretinism, is a condition associated with iodine deficiency and goiter, commonly characterised by mental deficiency, deafness, squint, disorders of stance and gait and stunted growth due to hypothyroidism. Paracelsus was the first to point out the relation between goitrous parents and their mentally disabled children. [9]

As a result of restricted diet, isolation, intermarriage, etc., as well as low iodine content in their food, children often had peculiar stunted bodies and retarded mental faculties, a condition later known to be associated with thyroid hormone deficiency. Diderot, in his 1754 Encyclopédie , described these patients as "crétins". In French, the term "crétin des Alpes" also became current, since the condition was observed in remote valleys of the Alps in particular. The word cretin appeared in English in 1779.

While reporting recent progress towards overcoming iodine-deficiency disorders worldwide, The Lancet noted: "According to World Health Organization, in 2007, nearly 2 billion individuals had insufficient iodine intake, a third being of school age." A conclusion was made that the single most preventable cause of intellectual disability is that of iodine deficiency. [10]

Fibrocystic breast changes

There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen. [11] [12] In rats treated with estradiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet. [11] [12] In a few studies, iodine supplementation had beneficial effects (such as reducing the presence of breast cyst, fibrous tissue plaques and breast pain) in women with fibrocystic breast changes. [11] [13] [ unreliable medical source? ]

Protective effects of iodine on breast cancer have been postulated[ by whom? ] from epidemiologic evidence and described in animal models. [14] [ unreliable medical source? ] [15] [ unreliable medical source? ] [16] In view of the antiproliferative properties of iodine in breast tissue, molecular iodine supplementation has been suggested as an adjuvant in breast cancer therapy. [16] [ citation needed ]

Risk factors

Following is a list of potential risk factors that may lead to iodine deficiency: [17]

  1. Low dietary iodine
  2. Selenium deficiency
  3. Pregnancy [18]
  4. Exposure to radiation
  5. Increased intake/plasma levels of goitrogens, such as calcium
  6. Sex (higher occurrence in women)
  7. Smoking tobacco
  8. Alcohol (reduced prevalence in users)
  9. Oral contraceptives (reduced prevalence in users)
  10. Perchlorates
  11. Thiocyanates
  12. Age (for different types of iodine deficiency at different ages)

Pathophysiology

Iodine accounts for 65% of the molecular weight of T4 and 59% of T3. There is a total of 15–20 mg of iodine in the human body, primarily concentrated in thyroid tissue and hormones. Thirty percent of iodine is distributed in other tissues, including the mammary glands, eyes, gastric mucosa, choroid plexus, arterial walls, the cervix, and salivary glands. In the cells of these tissues, iodide enters directly by sodium-iodide symporter (NIS).

Diagnosis

Sequence of 123-iodide human scintiscans after an intravenous injection, (from left) after 30 minutes, 20 hours, and 48 hours. A high and rapid concentration of radio-iodide is evident in the periencephalic and cerebrospinal fluid (left), salivary glands, oral mucosa and the stomach. In the thyroid gland, I-concentration is more progressive, also in the reservoir (from 1% after 30 minutes, to 5.8% after 48 hours, of the total injected dose. Sequence of 123-iodide total body human scintiscans.jpg
Sequence of 123-iodide human scintiscans after an intravenous injection, (from left) after 30 minutes, 20 hours, and 48 hours. A high and rapid concentration of radio-iodide is evident in the periencephalic and cerebrospinal fluid (left), salivary glands, oral mucosa and the stomach. In the thyroid gland, I-concentration is more progressive, also in the reservoir (from 1% after 30 minutes, to 5.8% after 48 hours, of the total injected dose.

The diagnostic workup of a suspected iodine deficiency includes signs and symptoms as well as possible risk factors mentioned above. A 24-hour urine iodine collection is a useful medical test, as approximately 90% of ingested iodine is excreted in the urine. [20] For the standardized 24-hour test, a 50 mg iodine load is given first, and 90% of this load is expected to be recovered in the urine of the following 24 hours. Recovery of less than 90% is taken to mean high retention, that is, iodine deficiency. The recovery may, however, be well less than 90% during pregnancy, and an intake of goitrogens can alter the test results. [21]

If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can alternatively be used. [20] However, the 24-hour test is found to be more reliable. [22]

A general idea of whether a deficiency exists can be determined through a functional iodine test in the form of an iodine skin test. In this test, the skin is painted with an iodine solution: if the iodine patch disappears quickly, this is taken as a sign of iodine deficiency. However, no accepted norms exist on the expected time interval for the patch to disappear, and in persons with dark skin color the disappearance of the patch may be difficult to assess. If a urine test is taken shortly after, the results may be altered due to the iodine absorbed previously in a skin test. [21]

Treatment

Iodine supplements Iodine pills.jpg
Iodine supplements

Iodine deficiency is treated by ingestion of iodine salts, such as found in food supplements. Mild cases may be treated by using iodized salt in daily food consumption, or drinking more milk, or eating egg yolks, and saltwater fish. For a salt and/or animal product restricted diet, sea vegetables (kelp, hijiki, dulse, nori (found in sushi)) may be incorporated regularly into a diet as a good source of iodine. [20] In more remote settings, iodized oil may be used. [23] [24]

The recommended daily intake of iodine for non-pregnant adults is 150 µg for maintenance of normal thyroid function. In pregnant women, the amount increases to 220 µg; in breastfeeding women, the amount is 290 µg. [20]

Prognosis

With iodine supplementation, goiters caused by iodine deficiency decrease in size in very young children and pregnant women. Generally, however, long-standing goiters caused by iodine deficiency respond with only small amounts of shrinkage after iodine supplementation, and patients are at risk for developing hyperthyroidism. [20]

Being pregnant while iodine-deficient additionally carries the risk of causing congenital iodine deficiency syndrome in the newborn. This disease can only be managed by lifelong administration of thyroxine (T4). [25]

Epidemiology

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Deaths due to iodine deficiency per million persons in 2012
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Disability-adjusted life year for iodine deficiency per 100,000 inhabitants in 2004. no data <50 50-100 100-150 150-200 200-250 250-300 300-350 350-400 400-450 450-500 500-750 >750 Iodine deficiency world map - DALY - WHO2004.svg
Disability-adjusted life year for iodine deficiency per 100,000 inhabitants in 2004.
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Iodine deficiency resulting in goiter occurs in 187 million people globally as of 2010 (2.7% of the population). [6] Certain areas of the world, due to natural deficiency and unavailability of iodine, are severely affected by iodine deficiency, which affects approximately two billion people worldwide. It is particularly common in the Western Pacific, South-East Asia and Africa. Among other nations affected by iodine deficiency, China and Kazakhstan have begun taking action, while Russia has not. Successful campaigns for the adoption of the use of iodized salt require education of salt producers and sellers and a communication campaign directed at the public. The cost of adding iodine to salt is negligible—"Only a few cents a ton." [27]

Iodine deficiency has largely been confined to the developing world for several generations, but reductions in salt consumption and changes in dairy processing practices eliminating the use of iodine-based disinfectants have led to increasing prevalence of the condition in Australia and New Zealand in recent years. A proposal to mandate the use of iodized salt in most commercial breadmaking was adopted in Australia in October 2009. [28] In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient. [29] The study's authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation". [29]

Micronutrient deficiencies, including iodine deficiency, impair the development of intelligence. Lacking iodine during human development causes a fall, in average, of 12 intelligence quotient (IQ) points in China. [30] A study of U.S. military data collected during the First and Second World Wars found that the introduction of salt iodization in the U.S. in the 1920s resulted in an increase in IQ, by approximately one standard deviation, for the quarter of the U.S. population most deficient in iodine, explaining about "one decade's worth of the upward trend in IQ" in the U.S. (i.e., the Flynn effect). [31] The same study documented "a large increase in thyroid-related deaths following the countrywide adoption of iodized salt, which affected mostly older individuals in localities with high prevalence of iodine deficiency". [31]

In iodine-deficient or mildly iodine-deficient areas of Europe, iodine deficiency is frequent during pregnancy despite the widespread use of iodised salt, posing risks to the neurodevelopment of foetuses. [32] In one study performed in a mildly iodine-deficient area, iodine deficiency was found to be present in more than half of breastfeeding women; in contrast, the majority of their newborns had iodine excess, mostly due to neonatal exposure to iodine-containing disinfectants. [33] A 2014 meta-analysis found that iodine supplementation "improves some maternal thyroid indices and may benefit aspects of cognitive function in school-age children, even in marginally iodine-deficient areas". [34]

Deficient populations

In areas where there is little iodine in the diet, typically remote inland areas and semi-arid equatorial climates where no marine foods are eaten, iodine deficiency gives rise to hypothyroidism, symptoms of which are extreme fatigue, goiter, mental slowing, depression, weight gain, and low basal body temperatures. [35]

Iodine deficiency is the leading cause of preventable mental retardation, a result which occurs primarily when babies or small children are rendered hypothyroidic by a lack of the element. The addition of iodine to table salt has largely eliminated this problem in the wealthier nations, but as of March 2006, iodine deficiency remained a serious public health problem in the developing world. [36]

Iodine deficiency is also a problem in certain areas of Europe. In Germany it has been estimated to cause a billion dollars in health care costs per year. [13] A modelling analysis suggests universal iodine supplementation for pregnant women in England may save £199 (2013 UK pounds) to the health service per pregnant woman and save £4476 per pregnant woman in societal costs. [37]

Iodine deficiency was previously a common disease in Norway, because the content of iodine in the drinking water was low. Before 1950 goiter was a widespread disease caused by iodine deficiency. [38] Up to 80 per cent of the population were affected in inland areas. In the coastal communities, saltwater fish were an important part of the diet, and because of the presence of iodine in seawater, goiter was less common than in the inland districts. From the 1950s, Norwegians started adding iodine to dairy cow feed. Since milk was an essential part of the Norwegian diet, the incidence of goiter decreased in the population. [38]

See also

Related Research Articles

<span class="mw-page-title-main">Congenital iodine deficiency syndrome</span> Medical condition

Congenital iodine deficiency syndrome (CIDS) is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It is one cause of underactive thyroid function at birth, called congenital hypothyroidism, historically referred to as cretinism (obsolete). If untreated, it results in impairment of both physical and mental development. Symptoms may include goiter, poor length growth in infants, reduced adult stature, thickened skin, hair loss, enlarged tongue, a protruding abdomen; delayed bone maturation and puberty in children; and mental deterioration, neurological impairment, impeded ovulation, and infertility in adults.

<span class="mw-page-title-main">Goitre</span> Medical condition

A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.

<span class="mw-page-title-main">Hyperthyroidism</span> Endocrine neck-gland secretes excess hormones affecting metabolism

Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism. Some, however, use the terms interchangeably. Signs and symptoms vary between people and may include irritability, muscle weakness, sleeping problems, a fast heartbeat, heat intolerance, diarrhea, enlargement of the thyroid, hand tremor, and weight loss. Symptoms are typically less severe in the elderly and during pregnancy. An uncommon but life-threatening complication is thyroid storm in which an event such as an infection results in worsening symptoms such as confusion and a high temperature; this often results in death. The opposite is hypothyroidism, when the thyroid gland does not make enough thyroid hormone.

<span class="mw-page-title-main">Thyroid</span> Endocrine gland in the neck; secretes hormones that influence metabolism

The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus (pl.: isthmi). The thyroid gland is a butterfly-shaped gland located in the neck below the Adam's apple. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid. The thyroid gland secretes three hormones: the two thyroid hormones – triiodothyronine (T3) and thyroxine (T4) – and a peptide hormone, calcitonin. The thyroid hormones influence the metabolic rate and protein synthesis and growth and development in children. Calcitonin plays a role in calcium homeostasis. Secretion of the two thyroid hormones is regulated by thyroid-stimulating hormone (TSH), which is secreted from the anterior pituitary gland. TSH is regulated by thyrotropin-releasing hormone (TRH), which is produced by the hypothalamus.

<span class="mw-page-title-main">Hypothyroidism</span> Endocrine disease

Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as poor ability to tolerate cold, a feeling of tiredness, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goitre. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.

<span class="mw-page-title-main">Congenital hypothyroidism</span> Medical condition

Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability. Infants born with congenital hypothyroidism may show no effects, or may display mild effects that often go unrecognized as a problem. Significant deficiency may cause excessive sleeping, reduced interest in nursing, poor muscle tone, low or hoarse cry, infrequent bowel movements, significant jaundice, and low body temperature.

<span class="mw-page-title-main">Hashimoto's thyroiditis</span> Autoimmune disease

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. A slightly broader term is autoimmune thyroiditis, identical other than that it is also used to describe a similar condition without a goiter.

<span class="mw-page-title-main">Iodised salt</span> Table salt preparation with iodide salts added

Iodised salt is table salt mixed with a minute amount of various salts of the element iodine. The ingestion of iodine prevents iodine deficiency. Worldwide, iodine deficiency affects about two billion people and is the leading preventable cause of intellectual and developmental disabilities. Deficiency also causes thyroid gland problems, including endemic goitre. In many countries, iodine deficiency is a major public health problem that can be cheaply addressed by purposely adding small amounts of iodine to the sodium chloride salt.

<span class="mw-page-title-main">Levothyroxine</span> Thyroid hormone

Levothyroxine, also known as L-thyroxine, is a synthetic form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to treat and prevent certain types of thyroid tumors. It is not indicated for weight loss. Levothyroxine is taken orally (by mouth) or given by intravenous injection. Levothyroxine has a half-life of 7.5 days when taken daily, so about six weeks is required for it to reach a steady level in the blood.

<span class="mw-page-title-main">Thyroid disease</span> Medical condition

Thyroid disease is a medical condition that affects the function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.

Food fortification or enrichment is the process of adding micronutrients to food. It can be carried out by food manufacturers, or by governments as a public health policy which aims to reduce the number of people with dietary deficiencies within a population. The predominant diet within a region can lack particular nutrients due to the local soil or from inherent deficiencies within the staple foods; the addition of micronutrients to staples and condiments can prevent large-scale deficiency diseases in these cases.

Goitrogens are substances that disrupt the production of thyroid hormones. This triggers the pituitary to release thyroid-stimulating hormone (TSH), which then promotes the growth of thyroid tissue, eventually leading to goiter.

Iodine deficiency is a widespread problem in western, southern and eastern parts of China, as their iodized salt intake level is much lower than the average national level. Iodine deficiency is a range of disorders that affect many different populations. It is estimated that IDDs affect between 800 million and 2 billion people worldwide; countries have spent millions of dollars in implementing iodized salt as a means to counteract the iodine deficiencies prevalent today. With China accounting for "40% of the total population", it bears a large portion of those who are iodine deficient.

<span class="mw-page-title-main">Thyroid hormones</span> Hormones produced by the thyroid gland

Thyroid hormones are any hormones produced and released by the thyroid gland, namely triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, derived from food. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre.

Selenium deficiency occurs when an organism lacks the required levels of selenium, a critical nutrient in many species. Deficiency, although relatively rare in healthy well-nourished individuals, can have significant negative results, affecting the health of the heart and the nervous system; contributing to depression, anxiety, and dementia; and interfering with reproduction and gestation.

<span class="mw-page-title-main">Iodine in biology</span> Use of Iodine by organisms

Iodine is an essential trace element in biological systems. It has the distinction of being the heaviest element commonly needed by living organisms as well as the second-heaviest known to be used by any form of life. It is a component of biochemical pathways in organisms from all biological kingdoms, suggesting its fundamental significance throughout the evolutionary history of life.

Thyroid disease in pregnancy can affect the health of the mother as well as the child before and after delivery. Thyroid disorders are prevalent in women of child-bearing age and for this reason commonly present as a pre-existing disease in pregnancy, or after childbirth. Uncorrected thyroid dysfunction in pregnancy has adverse effects on fetal and maternal well-being. The deleterious effects of thyroid dysfunction can also extend beyond pregnancy and delivery to affect neurointellectual development in the early life of the child. Due to an increase in thyroxine binding globulin, an increase in placental type 3 deioidinase and the placental transfer of maternal thyroxine to the fetus, the demand for thyroid hormones is increased during pregnancy. The necessary increase in thyroid hormone production is facilitated by high human chorionic gonadotropin (hCG) concentrations, which bind the TSH receptor and stimulate the maternal thyroid to increase maternal thyroid hormone concentrations by roughly 50%. If the necessary increase in thyroid function cannot be met, this may cause a previously unnoticed (mild) thyroid disorder to worsen and become evident as gestational thyroid disease. Currently, there is not enough evidence to suggest that screening for thyroid dysfunction is beneficial, especially since treatment thyroid hormone supplementation may come with a risk of overtreatment. After women give birth, about 5% develop postpartum thyroiditis which can occur up to nine months afterwards. This is characterized by a short period of hyperthyroidism followed by a period of hypothyroidism; 20–40% remain permanently hypothyroid.

Iodine is a chemical element with many uses in medicine, depending on the form. Elemental iodine and iodophors are topical antiseptics. Iodine, in non-elemental form, functions as an essential nutrient in human biology. Organic compounds containing iodine are also useful iodinated contrast agents in X-ray imaging.

<span class="mw-page-title-main">Creswell Eastman</span>

Creswell John Eastman is the Clinical Professor of Medicine at Sydney University Medical School, Principal of the Sydney Thyroid Clinic and Consultant Emeritus to the Westmead Hospital. Eastman is an endocrinologist and has directed or conducted research and public health projects into elimination of iodine deficiency disorders (IDD) in Malaysia, Indonesia, Laos, Cambodia, Thailand, several Pacific Islands, Hong Kong, China and Tibet and Australia. For his work in remote areas of China, he has been dubbed the "man who saved a million brains".

Thyroid disease in women is an autoimmune disease that affects the thyroid in women. This condition can have a profound effect during pregnancy and on the child. It also is called Hashimoto's thyroiditis (theye-royd-EYET-uhss). During pregnancy, the infant may be seriously affected and have a variety of birth defects. Many women with Hashimoto's disease develop an underactive thyroid. They may have mild or no symptoms at first, but symptoms tend to worsen over time. If a woman is pregnant and has symptoms of Hashimoto's disease, the clinician will do an exam and order one or more tests.

References

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  24. ↑ Medeiros-Neto, Geraldo; Rubio, Ileana G.S. (2016). "Iodine-Deficiency Disorders". Endocrinology: Adult and Pediatric. p. 1597. doi:10.1016/B978-0-323-18907-1.00091-3.
  25. ↑ Chorazy PA, Himelhoch S, Hopwood NJ, Greger NG, Postellon DC (July 1995). "Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature". Pediatrics . 96 (1 Pt 1): 148–50. PMID   7596704.
  26. ↑ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002.
  27. ↑ "In Raising the World's I.Q., the Secret's in the Salt", article by Donald G. McNeil, Jr., The New York Times , December 16, 2006.
  28. ↑ l "Iodine Fortification" Archived 2013-04-10 at the Wayback Machine , article appearing on March 5, 2013, from Food Standards.
  29. 1 2 Vanderpump, M. P.; Lazarus, J. H.; Smyth, P. P.; Laurberg, P; Holder, R. L.; Boelaert, K; Franklyn, J. A.; British Thyroid Association UK Iodine Survey Group (11 June 2011). "Iodine status of UK schoolgirls: a cross-sectional survey". The Lancet . 377 (9782): 2007–12. doi:10.1016/S0140-6736(11)60693-4. PMID   21640375. S2CID   2234051.
  30. ↑ Qian M, Wang D, Watkins WE, et al. (2005). "The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China". Asia Pacific Journal of Clinical Nutrition. 14 (1): 32–42. PMID   15734706.
  31. 1 2 James Feyrer; Dimitra Politi; David N. Weil (April 2017). "The Cognitive Effects of Micronutrient Deficiency: Evidence from Salt Iodization in the United States". Journal of the European Economic Association. 15 (2): 355–387. doi:10.1093/jeea/jvw002. PMC   6919660 . PMID   31853231.{{cite journal}}: CS1 maint: date and year (link)
  32. ↑ Trumpff, Caroline; De Schepper, Jean; Tafforeau, Jean; Van Oyen, Herman; Vanderfaeillie, Johan; Vandevijvere, Stefanie (2013). "Mild iodine deficiency in pregnancy in Europe and its consequences for cognitive and psychomotor development of children: A review" (PDF). Journal of Trace Elements in Medicine and Biology . 27 (3): 174–183. doi:10.1016/j.jtemb.2013.01.002. PMID   23395294.
  33. ↑ Yaman AK, Demirel F, Ermiş B, Pişkin IE (2013). "Maternal and neonatal urinary iodine status and its effect on neonatal TSH levels in a mildly iodine-deficient area". Journal of Clinical Research in Pediatric Endocrinology. 5 (2): 90–4. doi:10.4274/Jcrpe.997. PMC   3701928 . PMID   23748060.
  34. ↑ Taylor PN, Okosieme OE, Dayan CM, Lazarus JH (January 2014). "Therapy of endocrine disease: Impact of iodine supplementation in mild-to-moderate iodine deficiency: systematic review and meta-analysis". European Journal of Endocrinology (review). 170 (1): R1–R15. doi: 10.1530/EJE-13-0651 . PMID   24088547.
  35. ↑ Felig, Philip; Frohman, Lawrence A. (2001). "Endemic Goiter". Endocrinology & metabolism. McGraw-Hill Professional. ISBN   978-0-07-022001-0.
  36. ↑ "Micronutrients — Iodine, Iron and Vitamin A". UNICEF.
  37. ↑ Monahan, Mark; Boelaert, Kristien; Jolly, Kate; Chan, Shiao; Barton, Pelham; Roberts, Tracy E (2015-01-01). "Costs and benefits of iodine supplementation for pregnant women in a mildly to moderately iodine-deficient population: a modelling analysis" (PDF). The Lancet Diabetes & Endocrinology. 3 (9): 715–722. doi:10.1016/s2213-8587(15)00212-0. PMID   26268911.
  38. 1 2 "Fakta om jod" [Facts about iodine]. Folkehelseinstituttet (in Norwegian). Retrieved 2018-07-11.

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