Congenital iodine deficiency syndrome

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Congenital iodine deficiency syndrome
Other namesEndemic Cretinism [1]
Joseph le cretin - Fonds Trutat - MHNT.PHa.912.PR34 cropped.jpg
A man with congenital iodine deficiency syndrome
Specialty Endocrinology
Symptoms Goiter, mental impairment, poor growth, infertility, hair loss

Congenital iodine deficiency syndrome (CIDS), also called cretinism, [2] is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone production (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It is one cause of underactive thyroid function at birth, called congenital hypothyroidism. [3] 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, mental deterioration, neurological impairment, impeded ovulation, and infertility in adults. [4]

Contents

In developed countries, thyroid function testing of newborns has assured that in those affected, treatment with the thyroid hormone thyroxine is begun promptly. This screening and treatment successfully cures the disease. [5]

Signs and symptoms

Group of male and female patients of various ages with CIDS Cretin group.jpg
Group of male and female patients of various ages with CIDS

Iodine deficiency causes gradual enlargement of the thyroid gland, referred to as a goiter. Poor length growth is apparent as early as the first year of life. Adult stature without treatment ranges from 100 to 160 cm (3 ft 3 in to 5 ft 3 in), depending on severity, sex, and other genetic factors. Other signs include thickened skin, hair loss, enlarged tongue, and a protruding abdomen. [6] In children, bone maturation and puberty are severely delayed. In adults, ovulation is impeded and infertility is common. [7] [8]

Mental deterioration is common. Neurological impairment may be mild, with reduced muscle tone and motor coordination, or so severe that the person cannot stand or walk. Cognitive impairment may also range from mild to so severe that the person is nonverbal and dependent on others for basic care. Thought and reflexes are slower. [9] [10]

Cause

Disability-adjusted life years (DALY) lost from iodine deficiency in 2012 in proportion to a million people .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{} 52-163 181-217 221-221 222-310 320-505 512-610 626-626 653-976 984-1,242 1,251-3,159 Iodine deficiency world map-DALYs per million persons-WHO2012.svg
Disability-adjusted life years (DALY) lost from iodine deficiency in 2012 in proportion to a million people
  52–163
  181–217
  221–221
  222–310
  320–505
  512–610
  626–626
  653–976
  984–1,242
  1,251–3,159

Around the world, the most common cause of congenital iodine deficiency syndrome (endemic cretinism) [1] is dietary iodine deficiency.

Iodine is an essential trace element, necessary for the synthesis of thyroid hormones. Iodine deficiency is the most common preventable cause of neonatal and childhood brain damage worldwide. [11] Although iodine is found in many foods, it is not universally present in all soils in adequate amounts. Most iodine, in iodide form, is in the oceans, where the iodide ions are reduced to elemental iodine, which then enters the atmosphere and falls to earth in rain, introducing iodine to soils. Soil deficient in iodine is most common inland, in mountainous areas, and in areas of frequent flooding. It can also occur in coastal regions, where iodine might have been removed from the soil by glaciation, as well as leaching by snow, water and heavy rainfall. [12] Plants and animals grown in iodine-deficient soils are correspondingly deficient. Populations living in those areas without outside food sources are most at risk of iodine deficiency diseases. [13]

Diagnosis

Differential diagnosis

Dwarfism may also be caused by malnutrition or other hormonal deficiencies, such as insufficient growth hormone secretion, hypopituitarism, decreased secretion of growth hormone-releasing hormone, deficient growth hormone receptor activity and downstream causes, such as insulin-like growth factor 1 (IGF-1) deficiency. [14]

Prevention

There are public health campaigns in many countries which involve iodine administration. As of December 2019, 122 countries have mandatory iodine food fortification programs. [15]

Treatment

Congenital iodine deficiency has been almost eliminated in developed countries through iodine supplementation of food and by newborn screening utilizing a blood test for thyroid function. [5]

Treatment consists of lifelong administration of thyroxine (T4). Thyroxine must be dosed as tablets only, even to newborns, as the liquid oral suspensions and compounded forms cannot be depended on for reliable dosing. For infants, the T4 tablets are generally crushed and mixed with breast milk, formula milk or water. If the medication is mixed with formulas containing iron or soya products, larger doses may be required, as these substances may alter the absorption of thyroid hormone from the gut. [16] Monitoring TSH blood levels every 2–3 weeks during the first months of life is recommended to ensure that affected infants are at the high end of normal range. [17]

History

Cretinism (Styria), copper engraving, 1815 Cretinnen aus Steiermark, 1819 gez. Loder, gest. Leopold Muller.jpg
Cretinism (Styria), copper engraving, 1815

A goiter is the most specific clinical marker of either the direct or indirect insufficient intake of iodine in the human body. There is evidence of goiter, and its medical treatment with iodine-rich algae and burnt sponges, in Chinese, Egyptian, and Roman ancient medical texts. In 1848, King Carlo Alberto of Sardinia commissioned the first epidemiological study of congenital iodine deficiency syndrome, in northern Savoy where it was frequent. In past centuries, the well reported social diseases prevalent among the poorer social classes and farmers, caused by dietary and agricultural monocultures, were: pellagra, rickets, beriberi, scurvy in long-term sailors, and the endemic goiter caused by iodine deficiency. However, this disease was less mentioned in medical books because it was erroneously considered to be an aesthetic rather than a clinical disorder. [18]

Congenital iodine-deficiency syndrome was especially common in areas of southern Europe around the Alps and was often described by ancient Roman writers and depicted by artists. The earliest Alpine mountain climbers sometimes came upon whole villages affected by it. [19] The prevalence of the condition was described from a medical perspective by several travellers and physicians in the late 18th and early 19th centuries. [20] At that time the cause was not known and it was often attributed to "stagnant air" in mountain valleys or "bad water". The proportion of people affected varied markedly throughout southern Europe and even within very small areas; it might be common in one valley and not another. The number of severely affected persons was always a minority, and most persons were only affected to the extent of having a goitre and some degree of reduced cognition and growth. The majority of such cases were still socially functional in their pastoral villages. [21]

More mildly affected areas of Europe and North America in the 19th century were referred to as "goitre belts". The degree of iodine deficiency was milder and manifested primarily as thyroid enlargement rather than severe mental and physical impairment. In Switzerland, for example, where soil does not contain a large amount of iodine, cases of congenital iodine deficiency syndrome were very abundant and even considered genetically caused. As the variety of food sources dramatically increased in Europe and North America and the populations became less completely dependent on locally grown food, the prevalence of endemic goitre diminished. This is supported by a 1979 WHO publication which concluded that "changes in the origin of food supplies may account for the otherwise unexplained disappearance of endemic goitre from a number of localities during the past 50 years". [22]

The early 20th century saw the discovery of the relationships of neurological impairment with hypothyroidism due to iodine deficiency. Both have been largely eliminated in the developed world. [23]

Terminology

The term cretin was originally used to describe a person affected by this condition, but, as with words such as spastic and lunatic , it underwent pejoration and is now considered derogatory and inappropriate. [24] Cretin became a medical term in the 18th century, from an Occitan and an Alpine French expression, prevalent in a region where persons with such a condition were especially common (see below); it saw wide medical use in the 19th and early 20th centuries, and was a "tick box" category on Victorian-era census forms in the UK. The term spread more widely in popular English as a markedly derogatory term for a person who behaves stupidly. Because of its pejorative connotations in popular speech, current usage among health care professionals has abandoned the noun "cretin" referring to a person. The noun cretinism, referring to the condition, still occurs in medical literature and textbooks but its use is waning.[ citation needed ]

The etymology of cretin is uncertain. Several hypotheses exist. The most common derivation provided in English dictionaries is from the Alpine French dialect pronunciation of the word Chrétien ("(a) Christian"), which was a greeting there. According to the Oxford English Dictionary , the translation of the French term into "human creature" implies that the label "Christian" is a reminder of the humanity of the affected, in contrast to brute beasts. [25] Other sources suggest that Christian describes the person's "Christ-like" inability to sin, stemming, in such cases, from an incapacity to distinguish right from wrong. [26] [27]

Other speculative etymologies have been offered:

See also

Related Research Articles

<span class="mw-page-title-main">Goitre</span> Neck swelling due to enlarged thyroid gland

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> Clinical syndrome caused by excessive thyroid hormone

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 or Basedow’s disease, 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> Insufficient production of thyroid hormones by the thyroid gland

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, extreme fatigue, muscle aches, 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">Endemic goitre</span> Medical condition

Endemic goitre is a type of goitre that is associated with dietary iodine deficiency.

<span class="mw-page-title-main">Congenital hypothyroidism</span> Thyroid hormone deficiency present at birth

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.

Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body. It is a glycoprotein hormone produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.

<span class="mw-page-title-main">Myxedema</span> Extreme hypothyroidism

Myxedema is a term used synonymously with severe hypothyroidism. However, the term is also used to describe a dermatological change that can occur in hypothyroidism and (rare) paradoxical cases of hyperthyroidism. In this latter sense, myxedema refers to deposition of mucopolysaccharides in the dermis, which results in swelling of the affected area. One manifestation of myxedema occurring in the lower limb is pretibial myxedema, a hallmark of Graves disease, an autoimmune form of hyperthyroidism. Myxedema can also occur in Hashimoto thyroiditis and other long-standing forms of hypothyroidism.

<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">Pendred syndrome</span> Medical condition

Pendred syndrome is a genetic disorder leading to congenital bilateral sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism. There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone supplementation in case of hypothyroidism. It is named after Vaughan Pendred (1869–1946), the British doctor who first described the condition in an Irish family living in Durham in 1896. It accounts for 7.5% to 15% of all cases of congenital deafness.

<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.

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.

<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> Enlarged thyroid gland, causing symptoms of hyperthyroidism

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">Goitrogen</span> Substances that disrupt the production of thyroid hormones

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.

<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.

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.

Gabriella Morreale de Escobar was an Italian-born Spanish chemist who specialised in the thyroid. She and her husband Francisco Escobar del Rey showed that thyroid hormones cross the placenta during pregnancy and are essential for fetal brain development. She established a national newborn screening program for congenital hypothyroidism in Spain and helped to introduce iodised salt to prevent thyroid problems caused by iodine deficiency.

<span class="mw-page-title-main">Hypothyroidism in dogs</span> Medical condition

Hypothyroidism is an endocrine disorder in which the thyroid gland fails to produce sufficient thyroid hormones. Hypothyroidism is one of the most common endocrinopathies in dogs. It is either acquired or congenital.

References

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  20. ↑ See, for example, William Coxe, "Account of the Vallais, and of the Goiters and Idiots of that Country," Universal Magazine of Knowledge & Pleasure, vol. 67, Dec. 2, 1780.
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  22. ↑ De Maeyer, Lowenstein, Thilly (1979). The Control of Endemic Goitre. Geneva, Switzerland: WORLD HEALTH ORGANIZATION. pp. 9–10. ISBN   92-4-156060-6.{{cite book}}: CS1 maint: multiple names: authors list (link)
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  28. ↑ Medvei, VC (1993). The History of Clinical Endocrinology. Pearl River, New York: Parthenon Publishing Group.

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