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<!-- Definition and symptoms -->
'''Iodine deficiency''' is a lack of the [[trace element]] [[iodine]]. It may result in [[goiter]] (so-called [[endemic goiter]]), as well as [[cretinism]], which results in developmental delays and other health problems. Iodine deficiency is an important [[public health]] issue as it is a preventable cause of [[intellectual disability]].

<!-- Cause and diagnosis-->
[[Iodine]] is an essential [[trace element]]; the [[thyroid hormone]]s [[thyroxine]] and [[triiodothyronine]] contain iodine. In areas where there is little iodine in the diet—typically remote inland
[[Iodine]] is an essential [[trace element]]; the [[thyroid hormone]]s [[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''' gives rise to [[goiter]] (so-called [[endemic goiter]]), as well as [[cretinism]], which results in developmental delays and other health problems.
areas where no marine foods are eaten. Iodine deficiency is more common in mountainous regions of the world where food is grown in iodine-poor soil.


<!-- Prevention and treatment -->
Iodine deficiency is considered to be of particular relevance to [[public health]] because it is a preventable cause of [[intellectual disability]].
⚫
Prevention includes by 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.<ref>{{cite web |title=The Iodine Deficiency Disorders |url=http://www.thyroidmanager.org/Chapter20/20-frame.htm |work=Thyroid Disease Manager |author=François Delange, Basil Hetzel}}</ref> [[Seafood]] is also a well known source of iodine.<ref>[http://seaweed.ucg.ie/Nutrition/ Iodine in Seaweed<!-- Bot generated title -->]</ref>


<!-- Epidemiology -->
⚫
In some such areas, this is now combated by the addition of small amounts of iodine to table salt in form of [[sodium iodide]], [[sodium iodate]], [[potassium iodide]], and/or [[potassium iodate]]—this product is known as ''[[iodized salt]]''. Iodine compounds have also been added to other foodstuffs, such as flour, water and milk in areas of deficiency.<ref>{{cite web |title=The Iodine Deficiency Disorders |url=http://www.thyroidmanager.org/Chapter20/20-frame.htm |work=Thyroid Disease Manager |author=François Delange, Basil Hetzel}}</ref> [[Seafood]] is also a well known source of iodine.<ref>[http://seaweed.ucg.ie/Nutrition/ Iodine in Seaweed<!-- Bot generated title -->]</ref> Thus, iodine deficiency is more common in mountainous regions of the world where food is grown in iodine-poor soil.
Iodine deficiency resulting in goiter occurs 187&nbsp;million people globally as of 2010 (2.7% of the population).<ref name=LancetEpi2012>{{cite journal|last=Vos|first=T|title=Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010|journal=Lancet|date=Dec 15, 2012|volume=380|issue=9859|pages=2163–96|pmid=23245607|doi=10.1016/S0140-6736(12)61729-2|last2=Flaxman|first2=A. D.|last3=Naghavi|first3=M|last4=Lozano|first4=R|last5=Michaud|first5=C|last6=Ezzati|first6=M|last7=Shibuya|first7=K|last8=Salomon|first8=J. A.|last9=Abdalla|first9=S|last10=Aboyans|first10=V|last11=Abraham|first11=J|last12=Ackerman|first12=I|last13=Aggarwal|first13=R|last14=Ahn|first14=S. Y.|last15=Ali|first15=M. K.|last16=Alvarado|first16=M|last17=Anderson|first17=H. R.|last18=Anderson|first18=L. M.|last19=Andrews|first19=K. G.|last20=Atkinson|first20=C|last21=Baddour|first21=L. M.|last22=Bahalim|first22=A. N.|last23=Barker-Collo|first23=S|last24=Barrero|first24=L. H.|last25=Bartels|first25=D. H.|last26=Basáñez|first26=M. G.|last27=Baxter|first27=A|last28=Bell|first28=M. L.|last29=Benjamin|first29=E. J.|last30=Bennett|first30=D|display-authors=29}}</ref> It resulted in 2700 deaths in 2013 up from 2100 deaths in 1990.<ref name=GDB2013>{{cite journal|last1=GBD 2013 Mortality and Causes of Death|first1=Collaborators|title=Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.|journal=Lancet|date=17 December 2014|pmid=25530442|doi=10.1016/S0140-6736(14)61682-2}}</ref>


==Signs and symptoms==
==Signs and symptoms==
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Iodine deficiency resulting in goiter occurs 187&nbsp;million people globally as of 2010 (2.7% of the population).<ref name=LancetEpi2012>{{cite journal|last=Vos|first=T|title=Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010|journal=Lancet|date=Dec 15, 2012|volume=380|issue=9859|pages=2163–96|pmid=23245607|doi=10.1016/S0140-6736(12)61729-2|last2=Flaxman|first2=A. D.|last3=Naghavi|first3=M|last4=Lozano|first4=R|last5=Michaud|first5=C|last6=Ezzati|first6=M|last7=Shibuya|first7=K|last8=Salomon|first8=J. A.|last9=Abdalla|first9=S|last10=Aboyans|first10=V|last11=Abraham|first11=J|last12=Ackerman|first12=I|last13=Aggarwal|first13=R|last14=Ahn|first14=S. Y.|last15=Ali|first15=M. K.|last16=Alvarado|first16=M|last17=Anderson|first17=H. R.|last18=Anderson|first18=L. M.|last19=Andrews|first19=K. G.|last20=Atkinson|first20=C|last21=Baddour|first21=L. M.|last22=Bahalim|first22=A. N.|last23=Barker-Collo|first23=S|last24=Barrero|first24=L. H.|last25=Bartels|first25=D. H.|last26=Basáñez|first26=M. G.|last27=Baxter|first27=A|last28=Bell|first28=M. L.|last29=Benjamin|first29=E. J.|last30=Bennett|first30=D|display-authors=29}}</ref> 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 [[Pacific Ocean|Western Pacific]], [[South-East Asia]] and [[Africa]]. Among other nations affected by iodine deficiency, [[Peoples Republic of China|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."<ref name="mcneill">[http://www.nytimes.com/2006/12/16/health/16iodine.html "In Raising the World’s I.Q., the Secret's in the Salt"], article by Donald G. McNeil, Jr., ''[[The New York Times]]'', December&nbsp;16, 2006.</ref>
Iodine deficiency resulting in goiter occurs 187&nbsp;million people globally as of 2010 (2.7% of the population).<ref name=LancetEpi2012/> 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 [[Pacific Ocean|Western Pacific]], [[South-East Asia]] and [[Africa]]. Among other nations affected by iodine deficiency, [[Peoples Republic of China|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."<ref name="mcneill">[http://www.nytimes.com/2006/12/16/health/16iodine.html "In Raising the World’s I.Q., the Secret's in the Salt"], article by Donald G. McNeil, Jr., ''[[The New York Times]]'', December&nbsp;16, 2006.</ref>


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 there in October, 2009.<ref>[http://www.foodstandards.gov.au/scienceandeducation/factsheets/factsheets/iodinefortification/ l "Iodine Fortification"], article appearing on March 5, 2013 from ''Food Standards''.</ref> In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient.<ref name="UKdeficiency">{{cite journal|pmid=21640375|title=Iodine status of UK schoolgirls: a cross-sectional survey|journal=[[The Lancet]]|date=11 June 2011|doi=10.1016/S0140-6736(11)60693-4|volume=377|issue=9782|pages=2007–12|author1=Vanderpump|first1=M. P.|last2=Lazarus|first2=J. H.|last3=Smyth|first3=P. P.|last4=Laurberg|first4=P|last5=Holder|first5=R. L.|last6=Boelaert|first6=K|last7=Franklyn|first7=J. A.|author8=British Thyroid Association UK Iodine Survey Group}}</ref> The study's authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation".<ref name="UKdeficiency" />
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 there in October, 2009.<ref>[http://www.foodstandards.gov.au/scienceandeducation/factsheets/factsheets/iodinefortification/ l "Iodine Fortification"], article appearing on March 5, 2013 from ''Food Standards''.</ref> In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient.<ref name="UKdeficiency">{{cite journal|pmid=21640375|title=Iodine status of UK schoolgirls: a cross-sectional survey|journal=[[The Lancet]]|date=11 June 2011|doi=10.1016/S0140-6736(11)60693-4|volume=377|issue=9782|pages=2007–12|author1=Vanderpump|first1=M. P.|last2=Lazarus|first2=J. H.|last3=Smyth|first3=P. P.|last4=Laurberg|first4=P|last5=Holder|first5=R. L.|last6=Boelaert|first6=K|last7=Franklyn|first7=J. A.|author8=British Thyroid Association UK Iodine Survey Group}}</ref> The study's authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation".<ref name="UKdeficiency" />

Revision as of 21:47, 7 March 2015

Iodine deficiency

Iodine deficiency is a lack of the trace element iodine. It may result in goiter (so-called endemic goiter), as well as cretinism, which results in developmental delays and other health problems. Iodine deficiency is an important public health issue as it is a preventable cause of intellectual disability.

Iodine is an essential trace element; 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 more common in mountainous regions of the world where food is grown in iodine-poor soil.

Prevention includes by 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.[1] Seafood is also a well known source of iodine.[2]

Iodine deficiency resulting in goiter occurs 187 million people globally as of 2010 (2.7% of the population).[3] It resulted in 2700 deaths in 2013 up from 2100 deaths in 1990.[4]

Signs and symptoms

Goiter

Main article: 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 triiodiothyronine (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.[5] It is more common in third-world nations. 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.

Cretinism

Main article: Cretinism

Iodine deficiency is one of the leading causes of preventable mental handicaps worldwide, producing typical reductions in IQ of 10 to 15 IQ points. It has been speculated that deficiency of iodine and other micronutrients may be a possible factor in observed differences in IQ between ethnic groups: see race and intelligence for a further discussion of this controversial issue.

Cretinism is a condition associated with iodine deficiency and goiter, commonly characterised by mental deficiency, deaf-mutism, squint, disorders of stance and gait, stunted growth and hypothyroidism. Paracelsus was the first to point out the relation between goitrous parents and mentally retarded children.[6]

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 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. ... Thus iodine deficiency, as the single greatest preventable cause of mental retardation [sic], is an important public-health problem."[7] (In this context it is noted that the term "mental retardation" has been widely replaced by "intellectual disability".)

Fibrocystic breast changes

Main article: Fibrocystic breast changes

There is preliminary evidence that iodine deficiency enhances the sensitivity of breast tissue to estrogen.[8][9] In rats treated with estrodiol, iodine deficiency has been shown to lead to changes similar to benign breast changes that are reversible by increased iodine in the diet.[8][9] 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.[8][10][11][12][13]

Protective effects of iodine on breast cancer have been postulated from epidemiologic evidence and described in animal models.[12][14][15][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.[15]

Deficiency

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.[17]

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.[18] 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]

Iodine may also help prevent diseases of the oral and salivary glands.[19]

Risk factors

Following is a list of potential risk factors that may lead to iodine deficiency:[20]

  1. Low dietary iodine
  2. Selenium deficiency
  3. Pregnancy
  4. Exposure to radiation
  5. Increased intake/plasma levels of goitrogens, such as calcium
  6. Gender (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)

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.[21] 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[22] such as bromide.[23]

Pathophysiology

Iodine accounts for 65% of the molecular weight of T4 and 59% of the T3. 15–20 mg of iodine is concentrated in thyroid tissue and hormones, but 70% of the body's iodine is distributed in other tissues, including mammary glands, eyes, gastric mucosa, arterial walls, the cervix, and salivary glands. In the cells of these tissues, iodide enters directly by sodium-iodide symporter (NIS).

  • Venturi S, Guidi A, Venturi M (1996). "[Extrathyroid iodine deficiency disorders: what is the real iodine requirement?]"". Le Basi Razionali della Terapia. 16: 267–275.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Pellerin P (1961). "La tecnique d'autoradiographie anatomique a la temperature de l'azote liquide". Path Biol. 232 (9): 233–252.
  • Byeong-Cheol Ahn (2011). "Physiologic and False Positive Pathologic Uptakes on Radioiodine Whole Body Scan".

Diagnosis

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.[24] 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 urin 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.[25]

If a 24-hour urine collection is not practical, a random urine iodine-to-creatinine ratio can alternatively be used.[24] However, the 24-hour test is found to be more reliable.[26]

A general idea of whether a deficiency exists can be determined through a functional iodine test in fom 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 disappeance 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.[25]

Treatment

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.[24]

The recommended daily intake of iodine for adult women is 150–300 µg for maintenance of normal thyroid function; for men it is somewhat less at 150 µg.[24]

However, too high iodine intake, for example due to overdosage of iodine supplements, can have toxic side effects. It can lead to hyperthyroidism and consequently high blood levels of thyroid hormones (hyperthyroxinemia). In case of extremely high single-dose iodine intake, typically a short-term suppression of thyroid function (Wolff–Chaikoff effect) occurs.[27] Persons with pre-existing thyroid disease, elderly persons, fetuses and neonates, and patients with other risk factors are at a higher risk of experiencing iodine-induced thyroid abnormalities.[28] In particular, in persons with goiter due to iodine deficiency or with altered thyroid function, a form of hyperthyroidism called Jod-Basedow phenomenon can be triggered even at small or single iodine dosages, for example as a side effect of administration of iodine-containing contrast agents. In some cases, excessive iodine contributes to a risk of autoimmune thyroid diseases (Hashimoto's thyroiditis[29] and Graves' disease[30]).

Epidemiology

Disability-adjusted life year for iodine deficiency per 100,000 inhabitants in 2004.[31]
  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 resulting in goiter occurs 187 million people globally as of 2010 (2.7% of the population).[3] 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."[32]

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 there in October, 2009.[33] In a study of the United Kingdom published in 2011, almost 70% of test subjects were found to be iodine deficient.[34] The study's authors suggested an investigation regarding "evidence-based recommendations for iodine supplementation".[34]

It is well known that micronutrient deficiencies change the development of intelligence and iodine is no exception. Lacking in iodine during human development causes a fall, in average, of 12 IQ points in China.[35]

Scientists James Feyrer, Dimitra Politi, and David N. Weil have found in the U.S. that the proliferation of iodized salt increased IQ by 15 points in some areas. Journalist Max Nisen has stated that, with this type of salt becoming popular, that "the aggregate effect has been extremely positive."[36]

In iodine deficient or mildly iodine deficient areas in Europe, iodine deficiency is frequent during pregnancy despite the widespread use of iodised salt, posing risks to the neurodevelopment of foetuses.[37] In study performed in a midly 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.[38] 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."[39]

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.[24] Following the adaption of iodised salt in the United States in 1924 there was a gradual increase in average intelligence of 1 standard deviation, 15 points in iodine-deficient areas, 3.5 points nationally, but also an increase in deaths of older people in iodine-deficient areas due to hyperthyroidism.[40]

Research

In view of large-scale epidemiological studies of iodine levels in populations, a method of capillary electrophoresis with UV detection of iodine has been proposed.[41]

See also

References

  1. ^ François Delange, Basil Hetzel. "The Iodine Deficiency Disorders". Thyroid Disease Manager.
  2. ^ Iodine in Seaweed
  3. ^ a b Vos, T; Flaxman, A. D.; Naghavi, M; Lozano, R; Michaud, C; Ezzati, M; Shibuya, K; Salomon, J. A.; Abdalla, S; Aboyans, V; Abraham, J; Ackerman, I; Aggarwal, R; Ahn, S. Y.; Ali, M. K.; Alvarado, M; Anderson, H. R.; Anderson, L. M.; Andrews, K. G.; Atkinson, C; Baddour, L. M.; Bahalim, A. N.; Barker-Collo, S; Barrero, L. H.; Bartels, D. H.; Basáñez, M. G.; Baxter, A; Bell, M. L.; Benjamin, E. J.; et al. (Dec 15, 2012). "Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010". Lancet. 380 (9859): 2163–96. doi:10.1016/S0140-6736(12)61729-2. PMID 23245607.
  4. ^ GBD 2013 Mortality and Causes of Death, Collaborators (17 December 2014). "Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. doi:10.1016/S0140-6736(14)61682-2. PMID 25530442. {{cite journal}}: |first1= has generic name (help)CS1 maint: numeric names: authors list (link)
  5. ^ Andersson M, Takkouche B, Egli I, Allen HE, de Benoist B (2005). "Current global iodine status and progress over the last decade towards the elimination of iodine deficiency". Bull. World Health Organ. 83 (7): 518–25. PMC 2626287. PMID 16175826.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ T. E. C. Jr. M.D. (August 1, 1974). "Paracelsus on What the Physician Should Know". Pediatrics. 54 (2). American Academy of Pediatrics: 141. Retrieved 2008-12-05. {{cite journal}}: Italic or bold markup not allowed in: |journal= (help)
  7. ^ The Lancet (12 July 2008). "Iodine deficiency—way to go yet". The Lancet. 372 (9633): 88. doi:10.1016/S0140-6736(08)61009-0. PMID 18620930. Retrieved 2008-12-05.
  8. ^ a b c Cann, Stephen A.; van Netten, Johannes P.; van Netten, Christiaan (2000). "Hypothesis: iodine, selenium and the development of breast cancer". Cancer Causes and Control (review). 11 (2): 121–127. doi:10.1023/A:1008925301459. ISSN 0957-5243. PMID 10710195.
  9. ^ a b Joseph E. Pizzorno; Michael T. Murray (14 September 2012). Textbook of Natural Medicine. Elsevier Health Sciences. p. 1371. ISBN 1-4377-2333-0.
  10. ^ Ghent WR, Eskin BA, Low DA, Hill LP (October 1993). "Iodine replacement in fibrocystic disease of the breast". Canadian Journal of Surgery. Journal Canadien De Chirurgie (Comparative study). 36 (5): 453–60. PMID 8221402.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ Kessler JH (2004). "The effect of supraphysiologic levels of iodine on patients with cyclic mastalgia". The Breast Journal. 10 (4): 328–36. doi:10.1111/j.1075-122X.2004.21341.x. PMID 15239792.
  12. ^ a b "Iodine Monograph" (PDF). Alternative Medecine Review. 15 (3): 273–278. 2010.
  13. ^ a b Patrick L (2008). "Iodine: deficiency and therapeutic considerations". Altern Med Rev. 13 (2): 116–27. PMID 18590348.
  14. ^ Venturi S (October 2001). "Is there a role for iodine in breast diseases?". Breast (Edinburgh, Scotland). 10 (5): 379–82. doi:10.1054/brst.2000.0267. PMID 14965610.
  15. ^ a b Aceves C, Anguiano B, Delgado G (April 2005). "Is iodine a gatekeeper of the integrity of the mammary gland?". Journal of Mammary Gland Biology and Neoplasia (review). 10 (2): 189–96. doi:10.1007/s10911-005-5401-5. PMID 16025225.{{cite journal}}: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid16025225" was defined multiple times with different content (see the help page).
  16. ^ Stoddard FR, Brooks AD, Eskin BA, Johannes GJ (2008). "Iodine alters gene expression in the MCF7 breast cancer cell line: evidence for an anti-estrogen effect of iodine". International Journal of Medical Sciences. 5 (4): 189–96. doi:10.7150/ijms.5.189. PMC 2452979. PMID 18645607.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Felig, Philip; Frohman, Lawrence A. (2001). "Endemic Goiter". Endocrinology & metabolism. McGraw-Hill Professional. ISBN 978-0-07-022001-0.
  18. ^ "Micronutrients — Iodine, Iron and Vitamin A". UNICEF.
  19. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 19835108, please use {{cite journal}} with |pmid= 19835108 instead.
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