Goitre

Last updated

Goitre
Other namesGoiter
Thyroid, Diffuse Hyperplasia.jpg
Diffuse hyperplasia of the thyroid
Specialty Endocrinology

A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. [1] [2] A goitre can be associated with a thyroid that is not functioning properly.

Contents

Worldwide, over 90% of goitre cases are caused by iodine deficiency. [3] The term is from the Latin gutturia, meaning throat. Most goitres are not cancerous (benign), though they may be potentially harmful.

Signs and symptoms

A goitre can present as a palpable or visible enlargement of the thyroid gland at the base of the neck. A goitre, if associated with hypothyroidism or hyperthyroidism, may be present with symptoms of the underlying disorder. For hyperthyroidism, the most common symptoms are associated with adrenergic stimulation: tachycardia (increased heart rate), palpitations, nervousness, tremor, increased blood pressure and heat intolerance. Clinical manifestations are often related to hypermetabolism (increased metabolism), excessive thyroid hormone, an increase in oxygen consumption, metabolic changes in protein metabolism, immunologic stimulation of diffuse goitre, and ocular changes (exophthalmos). [4] Hypothyroid people commonly have poor appetite, cold intolerance, constipation, lethargy and may undergo weight gain. However, these symptoms are often non-specific and make diagnosis difficult.[ citation needed ]

According to the WHO classification of goitre by palpation, the severity of goitre is currently graded as grade 0, grade 1, grade 2. [5]

Causes

Worldwide, the most common cause for goitre is iodine deficiency, commonly seen in countries that scarcely use iodized salt. Selenium deficiency is also considered a contributing factor. In countries that use iodized salt, Hashimoto's thyroiditis is the most common cause. [6] Goitre can also result from cyanide poisoning, which is particularly common in tropical countries where people eat the cyanide-rich cassava root as the staple food. [7]

CausePathophysiologyResultant thyroid activityGrowth patternTreatmentIncidence and prevalencePrognosis
Iodine deficiency Hyperplasia of thyroid to compensate for decreased efficacyCan cause hypothyroidism DiffuseIodineConstitutes over 90% cases of goitre worldwide [3] Increased size of thyroid may be permanent if untreated for around five years
Congenital hypothyroidism Inborn errors of thyroid hormone synthesis Hypothyroidism
Goitrogen ingestion
Adverse drug reactions
Hashimoto's thyroiditis Autoimmune disease in which the thyroid gland is gradually destroyed. Infiltration of lymphocytes.HypothyroidismDiffuse and lobulated [8] Thyroid hormone replacement Prevalence: 1 to 1.5 in a 1000Remission with treatment
Pituitary disease Hypersecretion of thyroid stimulating hormone, almost always by a pituitary adenoma [9] DiffusePituitary surgeryVery rare [9]
Graves' disease—also called Basedow syndrome Autoantibodies (TSHR-Ab) that activate the TSH-receptor (TSHR) Hyperthyroidism Diffuse Antithyroid agents, radioiodine, surgeryWill develop in about 0.5% of males and 3% of femalesRemission with treatment, but still lower quality of life for 14 to 21 years after treatment, with lower mood and lower vitality, regardless of the choice of treatment [10]
Thyroiditis Acute or chronic inflammation Can be hyperthyroidism initially, but progress to hypothyroidism
Thyroid cancer Usually uninodularOverall relative 5-year survival rate of 85% for females and 74% for males [11]
Benign thyroid neoplasms Usually hyperthyroidismUsually uninodularMostly harmless [12]
Thyroid hormone insensitivity Secretional hyperthyroidism,
Symptomatic hypothyroidism		Diffuse

Diagnosis

Goitre with toxic adenoma Struma 004.jpg
Goitre with toxic adenoma

Goitre may be diagnosed via a thyroid function test in an individual suspected of having it. [13]

Types

A goitre may be classified either as nodular or diffuse. Nodular goitres are either of one nodule (uninodular) or of multiple nodules (multinodular). [14] Multinodular goiter (MNG) is the most common disorder of the thyroid gland. [15]

Growth pattern
Size

Treatment

Goitre is treated according to the cause. If the thyroid gland is producing an excess of thyroid hormones (T3 and T4), radioactive iodine is given to the patient to shrink the gland. If goitre is caused by iodine deficiency, small doses of iodide in the form of Lugol's iodine or KI solution are given. If the goitre is associated with an underactive thyroid, thyroid supplements are used as treatment. Sometimes a partial or complete thyroidectomy is required. [19]

Epidemiology

Disability-adjusted life year for iodine deficiency per 100,000 inhabitants in 2002. .mw-parser-output .div-col{margin-top:0.3em;column-width:30em}.mw-parser-output .div-col-small{font-size:90%}.mw-parser-output .div-col-rules{column-rule:1px solid #aaa}.mw-parser-output .div-col dl,.mw-parser-output .div-col ol,.mw-parser-output .div-col ul{margin-top:0}.mw-parser-output .div-col li,.mw-parser-output .div-col dd{page-break-inside:avoid;break-inside:avoid-column} .mw-parser-output .legend{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .legend-color{display:inline-block;min-width:1.25em;height:1.25em;line-height:1.25;margin:1px 0;text-align:center;border:1px solid black;background-color:transparent;color:black}.mw-parser-output .legend-text{} no data fewer than 50 50-100 100-150 150-200 200-250 250-300 300-350 350-400 400-450 450-500 500-800 more than 800 Iodine deficiency world map - DALY - WHO2002.svg
Disability-adjusted life year for iodine deficiency per 100,000 inhabitants in 2002.
  no data
  fewer than 50
  50–100
  100–150
  150–200
  200–250
  250–300
  300–350
  350–400
  400–450
  450–500
  500–800
  more than 800

Goitre is more common among women, but this includes the many types of goitre caused by autoimmune problems, and not only those caused by simple lack of iodine. [21]

Iodine mainly accumulates in the sea and in the topsoil. Before iodine enrichment programs, goiters was common in areas with repeated flooding or glacial activities, which erodes the topsoil. It is endemic in populations where the intake of iodine is less than 10 µg per day. [22]

Examples of such regions include the alpine regions of Southern Europe (such as Switzerland), the Himalayans, the Great Lakes basin, etc. As reported in 1923, all the domestic animals have goiter in some of the glacial valleys of Southern Alaska. It was so severe in Pemberton Meadows that it was difficult to raise young animals there. [23]

History

Goitre and congenital iodine deficiency syndrome in Styria, copper engraving, 1815 Cretinnen aus Steiermark, 1819 gez. Loder, gest. Leopold Muller.jpg
Goitre and congenital iodine deficiency syndrome in Styria, copper engraving, 1815
Woman in Miesbacher Tracht wearing a goitre choker Miesbacher gebirgstracht frau.jpg
Woman in Miesbacher Tracht wearing a goitre choker

Chinese physicians of the Tang dynasty (618–907) were the first to successfully treat patients with goitre by using the iodine-rich thyroid gland of animals such as sheep and pigs—in raw, pill, or powdered form. [24] This was outlined in Zhen Quan's (d. 643 AD) book, as well as several others. [24] One Chinese book, The Pharmacopoeia of the Heavenly Husbandman, asserted that iodine-rich sargassum was used to treat goitre patients by the 1st century BC, but this book was written much later. [24]

In the 12th century, Zayn al-Din al-Jurjani, a Persian physician, provided the first description of Graves' disease after noting the association of goitre and a displacement of the eye known as exophthalmos in his Thesaurus of the Shah of Khwarazm, the major medical dictionary of its time. [25] [26] The disease was later named after Irish doctor Robert James Graves, who described a case of goitre with exophthalmos in 1835. The German Karl Adolph von Basedow also independently reported the same constellation of symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively, [27] and by the English physician Caleb Hillier Parry (a friend of Edward Jenner) in the late 18th century. [28]

Paracelsus (1493–1541) was the first person to propose a relationship between goitre and minerals (particularly lead) in drinking water. [29] Iodine was later discovered by Bernard Courtois in 1811 from seaweed ash. [30]

Goitre was previously common in many areas that were deficient in iodine in the soil. For example, in the English Midlands, the condition was known as Derbyshire Neck. In the United States, goitre was found in the Appalachian, [31] [32] Great Lakes, Midwest, and Intermountain regions. The condition is now practically absent in affluent nations, where table salt is supplemented with iodine. However, it is still prevalent in India, China, [33] Central Asia, and Central Africa.

Goitre had been prevalent in the alpine countries for a long time. Switzerland reduced the condition by introducing iodized salt in 1922. The Bavarian tracht in the Miesbach and Salzburg regions, which appeared in the 19th century, includes a choker, dubbed Kropfband (struma band) which was used to hide either the goitre or the remnants of goitre surgery. [34]

Society and culture

In the 1920s wearing bottles of iodine around the neck was believed to prevent goitre. [35]

Notable cases

Heraldry

The coat of arms and crest of Die Kröpfner, of Tyrol showed a man "afflicted with a large goitre", an apparent pun on the German for the word ("Kropf"). [39]

See also

Related Research Articles

<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">Graves' disease</span> Autoimmune endocrine disease

Graves' disease, also known as toxic diffuse goiter, is an autoimmune disease that affects the thyroid. It frequently results in and is the most common cause of hyperthyroidism. It also often results in an enlarged thyroid. Signs and symptoms of hyperthyroidism may include irritability, muscle weakness, sleeping problems, a fast heartbeat, poor tolerance of heat, diarrhea and unintentional weight loss. Other symptoms may include thickening of the skin on the shins, known as pretibial myxedema, and eye bulging, a condition caused by Graves' ophthalmopathy. About 25 to 30% of people with the condition develop eye problems.

<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">Thyroidectomy</span> Surgical procedure involving partial or complete removal of the thyroid

A thyroidectomy is an operation that involves the surgical removal of all or part of the thyroid gland. In general surgery, endocrine or head and neck surgeons often perform a thyroidectomy when a patient has thyroid cancer or some other condition of the thyroid gland or goiter. Other indications for surgery include cosmetic, or symptomatic obstruction. Thyroidectomy is a common surgical procedure that has several potential complications or sequelae including: temporary or permanent change in voice, temporary or permanently low calcium, need for lifelong thyroid hormone replacement, bleeding, infection, and the remote possibility of airway obstruction due to bilateral vocal cord paralysis. Complications are uncommon when the procedure is performed by an experienced surgeon.

<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">Propylthiouracil</span> Medication used to treat hyperthyroidism

Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is typically only used when methimazole, surgery, and radioactive iodine is not possible. It is taken by mouth.

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.

The Jod-Basedow effect is hyperthyroidism following administration of iodine or iodide, either as a dietary supplement, for iodinated contrast medical imaging, or as a medication.

<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.

<span class="mw-page-title-main">Toxic multinodular goitre</span> Medical condition

Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism.

<span class="mw-page-title-main">De Quervain's thyroiditis</span> Medical condition

De Quervain's thyroiditis, also known as subacute granulomatous thyroiditis or giant cell thyroiditis, is a member of the group of thyroiditis conditions known as resolving thyroiditis. People of all ages and genders may be affected.

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

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

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

A thyroid adenoma is a benign tumor of the thyroid gland, that may be inactive or active as a toxic adenoma.

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

Thyroid nodules are nodules which commonly arise within an otherwise normal thyroid gland. They may be hyperplastic or tumorous, but only a small percentage of thyroid tumors are malignant. Small, asymptomatic nodules are common, and often go unnoticed. Nodules that grow larger or produce symptoms may eventually need medical care. A goitre may have one nodule – uninodular, multiple nodules – multinodular, or be diffuse.

Thyrotoxic myopathy (TM) is a neuromuscular disorder that develops due to the overproduction of the thyroid hormone thyroxine. Also known as hyperthyroid myopathy, TM is one of many myopathies that lead to muscle weakness and muscle tissue breakdown. Evidence indicates the onset may be caused by hyperthyroidism. Physical symptoms of TM may include muscle weakness, the breakdown of muscle tissue, fatigue, and heat intolerance. Physical acts such as lifting objects and climbing stairs may become increasingly difficult. If untreated, TM can be an extremely debilitating disorder that can, in extreme rare cases, lead to death. If diagnosed and treated properly the effects can be controlled and in most cases reversed leaving no lasting effects.

<span class="mw-page-title-main">Thyrotoxic periodic paralysis</span> Human disease

Thyrotoxic periodic paralysis (TPP) is a rare condition featuring attacks of muscle weakness in the presence of hyperthyroidism. Hypokalemia is usually present during attacks. The condition may be life-threatening if weakness of the breathing muscles leads to respiratory failure, or if the low potassium levels lead to abnormal heart rhythms. If untreated, it is typically recurrent in nature.

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.

<span class="mw-page-title-main">Amiodarone induced thyrotoxicosis</span> Form of hyperthyroidism

Amiodarone induced thyrotoxicosis (AIT) is a form of hyperthyroidism due to treatment with antiarrhythmic drug, amiodarone.

References

  1. ↑ "Thyroid Nodules and Swellings". British Thyroid Foundation. 11 September 2019.
  2. ↑ "Goitre - NHS Choices". NHS Choices. 19 October 2017.
  3. 1 2 Hörmann R (2005). Schilddrüsenkrankheiten Leitfaden für Praxis und Klinik (4., aktualisierte und erw. Aufl ed.). Berlin. pp. 15–37. ISBN   3-936072-27-2.{{cite book}}: CS1 maint: location missing publisher (link)
  4. ↑ Porth CM, Gaspard KJ, Noble KA (2011). Essentials of pathophysiology: Concepts of altered health states (3rd ed.). Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins.
  5. ↑ "Goitre as a determinant of the prevalence and severity of iodine deficiency disorders in populations". World Health Organization. 2014.
  6. ↑ Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN   978-1-4160-2973-1.
  7. ↑ "Toxicological Profile For Cyanide" (PDF). Atsdr.cdc.gov. Archived (PDF) from the original on 28 July 2004. Retrieved 16 March 2017.
  8. ↑ Babademez MA, Tuncay KS, Zaim M, Acar B, Karaşen RM (November 2010). "Hashimoto thyroiditis and thyroid gland anomalies". The Journal of Craniofacial Surgery. 21 (6): 1807–9. doi:10.1097/SCS.0b013e3181f43e32. PMID   21119426.
  9. 1 2 Thyrotropin (TSH)-secreting pituitary adenomas. By Roy E Weiss and Samuel Refetoff. Last literature review version 19.1: January 2011. This topic last updated: July 2, 2009
  10. ↑ Abraham-Nordling M, Törring O, Hamberger B, Lundell G, Tallstedt L, Calissendorff J, Wallin G (November 2005). "Graves' disease: a long-term quality-of-life follow up of patients randomized to treatment with antithyroid drugs, radioiodine, or surgery". Thyroid. 15 (11): 1279–86. doi:10.1089/thy.2005.15.1279. PMID   16356093.
  11. ↑ Numbers from EUROCARE, from Page 10 in: Grünwald F, Biersack HJ (2005). Thyroid cancer. Berlin: Springer. ISBN   978-3-540-22309-2.
  12. ↑ Bukvic BR, Zivaljevic VR, Sipetic SB, Diklic AD, Tausanovic KM, Paunovic IR (August 2014). "Improvement of quality of life in patients with benign goiter after surgical treatment". Langenbeck's Archives of Surgery. 399 (6): 755–64. doi:10.1007/s00423-014-1221-7. PMID   25002182. S2CID   34137703.
  13. ↑ "Goitre". nhs.uk. 19 October 2017. Retrieved 27 March 2019.
  14. ↑ "Nodular Goiter - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 6 March 2022.
  15. ↑ Feingold, K. R.; et al. (2000). "Multinodular Goiter". MDText.com. PMID   25905424.
  16. ↑ Frilling A, Liu C, Weber F (2004). "Benign multinodular goiter". Scandinavian Journal of Surgery. 93 (4): 278–81. doi:10.1177/145749690409300405. PMID   15658668. S2CID   38834260.
  17. ↑ "Toxic multinodular goitre - Symptoms, diagnosis and treatment | BMJ Best Practice". bestpractice.bmj.com.
  18. ↑ Gandolfi PP, Frisina A, Raffa M, Renda F, Rocchetti O, Ruggeri C, Tombolini A (August 2004). "The incidence of thyroid carcinoma in multinodular goiter: retrospective analysis". Acta Bio-Medica. 75 (2): 114–7. PMID   15481700.
  19. ↑ "Goiter – Simple". The New York Times.
  20. ↑ "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002.
  21. ↑ 1
  22. ↑ Goitre as a determinant of the prevalence and severity of iodine deficiency disorders in populations, World Health Organization - 2014
  23. ↑ Kimball, O. P. (February 1923). "The Prevention of Simple Goiter". American Journal of Public Health. 13 (2): 81–87. doi:10.2105/ajph.13.2.81-a. ISSN   0271-4353. PMC   1354367 . PMID   18010882.
  24. 1 2 3 Temple R (1986). The Genius of China: 3,000 Years of Science, Discovery, and Invention. New York: Simon and Schuster, Inc. pp. 134–5. ISBN   0-671-62028-2.
  25. ↑ Basedow's syndrome or disease at Who Named It? – the history and naming of the disease
  26. ↑ Ljunggren JG (August 1983). "[Who was the man behind the syndrome: Ismail al-Jurjani, Testa, Flagani, Parry, Graves or Basedow? Use the term hyperthyreosis instead]". Läkartidningen. 80 (32–33): 2902. PMID   6355710.
  27. ↑ Giuseppe Flajani at Who Named It?
  28. ↑ Hull G (June 1998). "Caleb Hillier Parry 1755-1822: a notable provincial physician". Journal of the Royal Society of Medicine. 91 (6): 335–8. doi:10.1177/014107689809100618. PMC   1296785 . PMID   9771526.
  29. ↑ "Paracelsus" Britannica
  30. ↑ Davy, Humphry (1 January 1814). "VI. Some experiments and observations on a new substance which becomes a violet coloured gas by heat". Philosophical Transactions of the Royal Society of London. 104: 74–93. doi:10.1098/rstl.1814.0007. S2CID   109845199.
  31. ↑ "Iodine Deficiency".
  32. ↑ Hollingsworth, Dorothy R. (1977). "Kentucky Appalachian Goiter Without Iodine Deficiency". American Journal of Diseases of Children. 131 (8): 866–869. doi:10.1001/archpedi.1977.02120210044010. PMID   888801.
  33. ↑ "In Raising the World's I.Q., the Secret's in the Salt", article by Donald G. McNeil, Jr., December 16, 2006, The New York Times
  34. ↑ Wissen, Planet (16 March 2017). "Planet Wissen".
  35. ↑ "ARCHIVED – Why take iodine?". Nrc-cnrc.gc.ca. 30 September 2011. Retrieved 1 November 2012.
  36. ↑ Lahita RG, Yalof I (20 July 2004). Women and Autoimmune Disease. HarperCollins. p. 158. ISBN   978-0-06-008149-2.
  37. ↑ Altman LK (14 September 1991). "A White House Puzzle: Immunity Ailments". The New York Times. Doctors Say Bush Is in Good Health
  38. ↑ Altman LK (28 May 1991). "The Doctor's World; A White House Puzzle: Immunity Ailments". The New York Times.
  39. ↑ Fox-Davies AC (1904). The Art of Heraldry: An Encyclopædia of Armory. New York and London: Benjamin Blom, Inc. p. 413.
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