Iodine is a halogen element that is the essential raw material for the synthesis of the thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) — the hormones that regulate basal metabolic rate, thermogenesis, heart rate, cardiac output, and brain development, and that are essential for normal growth and cognitive function. Iodine is taken up by the thyroid follicular cells from the blood via the sodium iodide symporter (NIS) and is oxidised by thyroid peroxidase (TPO) to iodine, which is then covalently attached to the tyrosine residues on thyroglobulin (the precursor protein of T3 and T4) in a reaction called iodination. The iodinated tyrosine residues are then coupled to form T3 and T4, which are stored in the colloid of the thyroid follicle as part of the thyroglobulin molecule and released into the blood upon stimulation by thyroid-stimulating hormone (TSH). The iodine-dependent synthesis of thyroid hormones is one of the most important metabolic pathways in human physiology, and its dysregulation is implicated in some of the most common diseases of endocrinology, including hypothyroidism, hyperthyroidism, goitre, and the cognitive impairment that is associated with iodine deficiency.
Global Iodine Deficiency
Iodine deficiency is the most common nutritional deficiency in the world — it affects approximately 2 billion people, primarily in the mountainous regions of South Asia, Sub-Saharan Africa, and Latin America where the soil is iodine-deficient and where the diet is low in iodine-rich foods. The clinical manifestations of iodine deficiency range from mild (subtle cognitive impairment, reduced energy, cold intolerance) to severe (goitre, cretinism, intellectual disability, growth retardation). The most severe form of iodine deficiency is cretinism — a condition of irreversible intellectual disability and physical stunting that occurs when iodine deficiency is severe and prolonged during pregnancy and early childhood. Cretinism is characterised by severe hypothyroidism, growth retardation, deafness, and in the neurological form, by the spasticity, the strabismus, and the other neurological signs that result from brain damage during development. The prevention of cretinism and of the other manifestations of iodine deficiency through salt iodisation and through the supplementation of the diet with iodine is one of the most successful public health interventions in history — it has virtually eliminated cretinism and has dramatically reduced the prevalence of goitre in the countries that have implemented universal salt iodisation programmes.
The goitre (enlargement of the thyroid gland) that is associated with iodine deficiency is the direct result of the feedback regulation of TSH secretion by T3 and T4. When iodine is deficient and T3/T4 synthesis is impaired, the reduced negative feedback of T3/T4 on the pituitary leads to an increase in TSH secretion, and the elevated TSH stimulates the proliferation of the thyroid follicular cells (the goitrogenic effect of TSH). This TSH-driven proliferation of the thyroid gland produces the glandular enlargement that is the hallmark of goitre, and it can progress to the multinodular goitre that is associated with the compression of the trachea and oesophagus that produces the symptoms of tracheal and oesophageal compression in long-standing goitre.
The Iodine Deficiency Disorders
The spectrum of clinical manifestations that results from iodine deficiency is collectively called the iodine deficiency disorders (IDD) and includes goitre, hypothyroidism, cretinism (both neurological and myxoedematous forms), the increased risk of stillbirth and miscarriage, the increased risk of infant mortality, and the cognitive impairment that is associated with even mild iodine deficiency during pregnancy and lactation. The cognitive impairment that is associated with mild iodine deficiency is one of the most important and least appreciated aspects of IDD — even in the absence of the overt cretinism that is associated with severe deficiency, mild-to-moderate iodine deficiency during pregnancy and early childhood is associated with a reduction in IQ of approximately 10-15 points and with the cognitive deficits that affect attention, memory, and executive function. The prevention of IDD through universal salt iodisation is one of the most cost-effective public health interventions available — it costs approximately /usr/bin/bash.05 per person per year and has been estimated to prevent the loss of approximately 1.5 billion IQ points globally.
Practical Application
For general iodine supplementation (for the prevention and treatment of iodine deficiency), the evidence-based approach is to ensure adequate iodine intake from iodised salt (which should contain 20-40mg of iodine per kg of salt, which is the level that is recommended by the WHO for universal salt iodisation programmes) and from dietary sources (seafood, fish, shellfish, seaweed, and the dairy products from iodine-supplemented cattle). The RDA for iodine is 150mcg daily for adults, 220mcg daily for pregnant women, and 290mcg daily for lactating women. The tolerable upper intake level (UL) for iodine is 1,100mcg daily for adults, and chronic intake above this level should be avoided because it can produce the iodine-induced hyperthyroidism (the Jod-Basedow phenomenon) and the iodine-induced hypothyroidism (the Wolff-Chaikoff effect) that are associated with excessive iodine intake. For comprehensive thyroid support, iodine pairs well with selenium (which is required for the deiodinase enzymes that convert T4 to T3 and which protects the thyroid from oxidative damage), with tyrosine (which is the amino acid backbone of the thyroid hormones and which is the substrate for the TPO-catalysed iodination reaction), with zinc (which is required for the synthesis of TSH and for the function of the thyroid hormone receptor), and with iron (which is required for the activity of thyroid peroxidase and which is often deficient in people with hypothyroidism).
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