Iodine deficiency disorder (IDD), is one of the most common cause of preventable mental retardation and brain damage in the world. Iodine deficiency can cause thyroid enlargement and goiter, hypothyroidism, and pregnancy-related problems such as miscarriages, stillbirth, preterm delivery, and congenital abnormalities in their babies. Even mild iodine deficiency during pregnancy maybe associated with low intelligence in children (ICCIDD, ATA).
Causes of IDD:
During pregnancy the hormonal change can affect the thyroid function and increases urinary iodide excretion. Accordingly, the requirement for T4 is increased by approximately 50% mainly due estrogen -induced rise of thyroxine-binding globulin and to increased peripheral T4 metabolism due to T4 placental deiodination. Therefore T4 level should be increased during gestation to 200-300 μg/d to sustain the augmented maternal T4 requirement and fetal thyroid function and to compensate for the enhanced urinary iodide excretion, otherwise IDD can be experienced and leads to maternal and fetal goiter, miscarriages, stillbirths, reduced fetal growth, neonatal hypothyroidisms, and damaged reproduction in adult life.
Iodine as iodide is widely but not evenly distributed in the earth's environment, most iodide found in the ocean and seawater oxidize into volatile element and evaporate into the atmosphere and then return to the soil through the rain. However, this cycle in many regions is slow and incomplete and so the soils and groundwater become deficient in iodine content. Thus, crops grown in these soils will be low in iodine concentration and man and animals consuming food grown in these soils become deficient in iodine which is the main cause of IDD.
Even with consumption of iodized salt, cases of IDD are detected. Consequently, this due to low iodine intake resulted from iodine loss from the salt, which caused by high humidity combined with porous packing. [4]
IDD may be caused by high intake of iodine, as many thyroid processes are inhibited when iodine intake becomes high. [3]
Health Consequences of IDD:
70-80 % of iodine is present in the thyroid gland. 90% of it is bound to thyroglobulin(TG).Iodide, in the thyroid gland, is oxidized by peroxidase to I2 then it reacts with the thyrosin residues of the glycoprotein Tg to monoiodotyrosin (MIT) or diiodotyrosin (DIT).MIT and DIT react further to active thyroid hormones thyroxine(T4) and triiodothyronin (T3)
During pregnancy, the maternal T4 level may decrease due to the hormonal changes which affect thyroid function status and the increase level of urinary iodide excretion so probably iodine deficiency can be experienced by both mother and fetus.
Severe Iodine deficiency during pregnancy causes the increase risk of stillbirth, spontaneous abortion and congenital abnormalities. The most severe of these abnormalities is cretinism, which is a state of mental retardation mostly in combination with dwarfism, deaf-mutism and spasticity. These conditions are largely irreversible. The reduction in maternal T4 transfer from mother to foetus can cause iodine deficiency in the foetus. During the first trimester, the feotus is completely dependent on maternal T4. This T4 is converted using type II deiodiase into the active form T3. Accordingly, T3 providing the developing foetal brain.Only at the second trimester,foetal thyroid function becomes active.in the case of mild-to-moderate iodine deficiency during pregnancy, the circulating level of T3 remain normal and circulating level of TSH doesn't increase as occure in hypothyroidism. Because mild-to-moderate hypothyroxinaemic mothers have normal levels of circulating TSH , they will be considered as euthyroid.However, the amount of maternal T4 available to the foetus would be insufficient fro its normal neurodevelopment. Thyroid hormones play an important role in various neurobiological processes, such as synaptogensis, neurogensis, neuronalmigtation axon and dendrite formation, myelination and neurotransmission.In utero , the effects of thyroid hormone deficiency are varying according to the pregnancy trimesters. During the first and second trimester of pregnancy, throid hormone deficiency will affect the visual attention, visual processing , visuospatial skills and fine motor skills. During the second and third trimester, gross motor skills, memory and motor function will be affected.Postnatal thyroid hormone deficiency would affect basically language and verbal development, as well as attention and memory skills. [13]
Iodine has an important role in thyroid metabolism. Thyroid hormones are required for normal metabolic function in humans, and regulate development, growth and differentiation in many systems and physiological processes. T4 is synthesized in thyroid gland using I2 as precursor.T4 is converted into the active hormoneT3 [13]. Thyroid enlargement (goiter) is the most visible effect of ID. Hence, iodine deficiency occur due to insufficient dietary iodine intake, the secretion of thyroid stimulating hormone ( TSH) increase in an effoet to maximize uptake of available iodine in order to synthesize more thyroid hormones. at the same time, TSH stimulate thyroid hypertrophy and hyperplasia [4]. Thyroid dysfunction occurs when the thyroid gland doesn't supply the proper amount of hormones needed by the body.The enlargement of thyroid gland occur and charcterised by diffuse, homogeneous enlagment and soft nodules that grow slowly within the thyroid gland. [14] & [4]. At the early stage of goiterogensis, goiters diffuse and over the time diffused goiters grow and become nodular and refer to as multinodular toxic goiter. Large goiter can obetract the trachea and esophagusand many damage the recurrent laryngeal nerves and cause hoarseness [4]. Concomitantly, thyroid gland becomes autonomous, that is, thyiod hormones secretion becomes independent of thyreotropin secretion. Therefore, the patient gradually develops subclinical hyperthyroidism and eventually overt hyperthyroidism. [13]
Thyroid gland secrete three type of hormones: thyroxine (T4), triiodothyronine(T3), and calcitonin. Calcitonin involves with parathyroid hormone and vitamin D in regulating the serum level of calcium, phosphorus and skeletal remodeling [16]. Unlike calcitonin, T4 and T3 hormones regulate the metabolic processes throughout the body , energy and heat production(1). T4 and T3 also facilitate healthy development of the central nrvous system,somatic growth, puberty and regulate synthesis of proteins important for hepatic,cardiac, neurological and muscular function[17]. Serum level of T4 and T3 hormones are controlled through a severfeedback mechanism mediated by hypothalamic-pituitary-thyroid axis. The secretion of thyroid -stimulating hormone(TSH) is regulated by the interaction of thyroid -releasing hormone(TRH) and inhibatory factor(somatostatin). T4 and T3 hormones act on both pituitary to inhibit the release of TSH and on the hypothalamic level to stimulate somatostatin release. As T3 is more potent than T4, T4 is converted to T3 in the liver, kidneys, heart and in the pituitary and hypothalamus. Many conditions can affect thyroid gland function such as drugs, illnesses, thyroid function and pituitary disorders. normally , thyrotropin -releasing hormone(TRH) is secreted by hypothalamus in response to many factors such as stress , illnesses, low levels of T4 and T3 hormones which in turn TRH stimulate the release of thyroid -stimulating hormone(TSH) from pituitary [16]. With insufficient dietary iodine intake, the serum level of T4 falls. Accordingly, the pituitary gland response to this low level of circulating T4 by releasing more TSH, in turn TSH stimulate each cell to increase iodine intake and thyroid hormones synthesis and secretion. Increased TSH level with reduction of iodine stores within the thyroid gland will result in increased T3 production relative to T4 production. Therefore, enlargement of the thyroid gland begins as an adaptive process to low iodine intake resulting in goiter. In some cases, goiter nodules become autonomous and secret thyroid hormones regardless of the TSH level. Autonomous nodules may cause hyperthyroidism [18]. Symptoms include palpations, heat intolerance, increased sweating, increased appetite, weight loss, insomnia, mood swings, frequent bowel movement, diarrhea, pruritus, nervousness, hand tremor, decrease tolerance to exercise, shortness of breath, eye symptoms, double vision and retoorbital pain [19].
Cretinism includes two syndromes: a more common neurological disorder with brain damage, deaf mutism, squint and spastic paresis of the leg and less common syndrome of severe hypothyroidism, growth retardation and less severe mental defect. Both conditions are due dietary iodine deficiency in which the thyroid gland is underactive during infancy and childhood. Clinical manifestations differ between neurological and hypothyroid cretinism. Neurological Cretins is common in areas of severe iodine deficiency. The obvious clinical features include mental retardation with the following neurological defects:
Defects of hearing and speech
Squint
Predominant neurological signs: impaired voluntary motor activity involving spastic diplegia or paresis of the lower limbs.
Characteristic disorders of stance and gait of verying degree, including spastic gait and ataxia with serious effect on standing and walking, so that affected children are dependent on the stick.
Hypothyroid Cretins: severe or long standing hypothyroidism is predominant in this type with the following features: dwarfism, myxoedema, dry swollen or thickened skin, sparseness of hair and nails, deep hoarse voice, sexual retardation, weak abdominal muscles, retarded maturation of body parts, skeletal retardation, inactive bowel function and delayed tendon reflexes. The typical feature is incomplete maturation of the face: wide- set eyes, saddle- nose deformity with retarded maturation of nose-orbital configurations, mandibular atrophy and thickened lips.
The mental deficiency in the neurological type is more severe than in the hypothyroid type. The prevalence of goiter in the hypothyroid cretins is much lower than in neurological type. [20]
Hyperthyroidism is the most common pathological hormone deficiency. Hypothyroidism is more common among women than men and its incidence increases with age, especially after the onset of middle life [21]. In moderate to severe iodine deficiency hypothyroidism occurs as a result of lacking the substrate (iodine) for thyroid hormones production (T4 and T3 [22]. Hypothyroidism is classified according to its time or onset (congenital or acquired), the level of endocrine dysfunction (primary or secondary) and its severity (overt [clinical] or mild [subclinical]). Worldwide, the most common cause of congenital hypothyroidism is endemic iodine deficiency [21]. Iodine deficiency causes thyroid hormones deficiency; because no thyroid hormones inhibit pituitary gland release TSH, thyroid is over stimulated and enlarges but function below normal (hypothyroidism) .Clinical symptoms and signs in adult with hypothyroidism include: myxedema-low metabolic rate, sensivity to cold, sluggishness, poor appetite, swollen tissue, weight gain, mental dullness. Hypothyroidism in infants can have other symptoms and signs which can include: cretinism-stunted growth, abnormal bone formation, mental retardation, low body temperature, sluggishness.
Sources of iodine:
The iodine content in fish is considered relatively high range 0.39-6.9 μg/g; nevertheless, the iodine concentration varies widely between fishes from same species, depending on the iodine concentration in water. Therefore, Marine fish has higher (5-10 time) iodine concentration than freshwater fish. [5]
Iodine is naturally present in seawater, and due to the ability of the seaweed to concentrate inorganic species from seawater like iodine, seaweed are one of the highest sources of iodine with a ranging from 55 to 2000 μg g−1 according to the seaweed specie and the season. Iodine present in seaweed as water-soluble iodine, soluble organic iodine, iodide (I−) and iodate (IO3−). Consequently, the percentage of water-soluble iodine is within 16-99% of the total iodine, while the organic soluble iodine varies from 5 to 37% in seaweed. [7], [8]
Milk and dairy products and eggs have high iodine concentration ranging from 0.15-2.1 μg/g. Milk is not naturally have high concentration of iodine, moreover, the main reason for it is the use of organic iodine compounds for the prevention and treatments of foot rot disease in dairy cattle. The high iodine concentration in milk is partly due to the iodination of cattle feed which is used in the dairy industry. Another reason is for high iodine concentration is through the disinfection of teats by iodine containing agent. Also iodine solution is used to sterilize the mechanical systems that used to extract milk from cows, and iodine residue may pass in to milk. As in milk iodine is past to egg through supplementing laying hens feed with iodine. [5], [6]
The cheese content of iodine doesn't reflect the iodine content in milk that it's produced from. When cheese is manufactured the curd is separated from whey and almost all the iodine in milk is in the whey which caused iodine loss. Nevertheless, iodinated salt is added during cheese manufacturing which effect the iodine concentration in cheese. [5]
Even though wheat grains did not derive much iodine from the soil, bakery products are now considered to be a high source of iodine, and that subsequent to the use of iodized salt in baking. Also potassium and calcium iodate are used as dough conditioners, in which it's improve the texture, appearance, and shelf-life of baked products, therefore some bread slice contain more than 300 μg . Another additive FD&C Red #3 (erythrosine), it's a dye used in ready-to-eat cereals and other foods, is 58% iodine by weight. [9] [12]
Iodized salt is major source of iodine. There are two forms in which iodine is added to salt potassium iodate or potassium iodide. Even though, in practice long term storage of iodized salt under adverse conditions cause in some loss of iodine, due to inverse disproportional reaction. An adequate iodine concentration in household salt should be range 15-40 mg iodine kg−1 . [10], [11].
The iodine concentration in plant varies from species to species, and within the same species depending in iodine concentration in soil. In general plant foods have low concentration of iodine about 0.002-0.7 μg/g, with the exception of herbs, leafy and nightshade vegetables. Also it's detected that Mushrooms have high iodine concentration, and fair amounts of iodine were also found in nuts. [5]
Mechanism to combat IDD:
The most effective way to combat IDD is salt iodization. Universal salt iodization (USI) is a term used to describe the iodization of all salts for human (food industry and household) and livestock feeds. More than two-thirds (68%) of households worldwide are using salt containing >15 mg iodine kg−1 salt, and out of 123 countries, only 34 countries have attained salt iodisation with the international goal of at least 90% of households consuming adequately iodised salt. Even though in country with successful salt iodization program, USI is rarely achieved and that because food industries are often reluctant to use iodized salt, and many countries do not iodize salt for livestock (low iodine in milk and eggs). WHO/UNICEF/ICCIDD recommends that iodine is added to salt at a level of 20-40 mg iodine /kg salt. Nevertheless, iodine fortification levels in salt differ substantially among countries. In European the iodine levels range from 8 to 69 mg iodine per kg salt, while in some African countries iodine levels go up to 100 mg iodine per kg salt. The level of iodine in salt is usually adjusted to provide 100 μg of iodine per day, taking in account iodine taken from natural sources. Iodine is added to salt either in the form of potassium iodide (KI) or potassium iodate (KIO3). Potassium iodate (KIO3) is more stable than potassium iodide (KI) in case of salt impurities, humidity, and porous packaging [41] L.L. Diosady, J.O. Alberti, M.G.V. Mannar and T.J. Stone, Stability of iodine in iodized salt used for correction of iodine-deficiency disorders, I, Food Nutr Bull 18 (1997), pp. 388-396. View Record in Scopus | Cited By in Scopus (21), therefore it is the recommended form to be used in tropical countries and those with low quality salt. Iodine is added to salt after the salt is dried, moreover, there is two techniques that used: first one is the wet method, where a solution of KIO3 is dripped or sprayed at a regular rate on to salt passing by on a conveyor belt; the second one is the dry method, where KI or KIO3 powder is sprinkled over the dry salt. Salt should be packaged in low-density polyethylene bags, as high humidity combined with porous packing cause about 90% losses of iodine in 1 year of storage in high-density polyethylene bags, compared to 10-15% low-density polyethylene bags. Salt iodization is the most cost effective way of delivering iodine and improving its consumption in iodinedeficient populations. Before the development of salt iodization program, the annual potential losses attributable to ID in the developing country have been estimated to be US$35.7 billion when the estimated for salt iodization is US$0.5 billion per year, i.e., a 70:1 benefit: cost ratio. [4], [9], [23]
In some regions, mostly remote areas where communications are poor or have small-scale salt producers, salt iodization may not be practical way to prevent iodine deficiency. Oil iodization is another way to provide the necessary iodine. Iodized oil is prepared by esterification of the unsaturated fatty acids in seed or vegetable oils, and then addition iodine to the double bonds. This oil can be given orally or by intramuscular injection, which is have longer duration of action, where as oral method is more common because its simpler. The regular dose is 200-400 mg of iodine/ year, which is often recommended for women of child-bearing age, pregnant women, and children. If iodized oil is given in first and second trimester of pregnancy, it will decrease the prevalence of neurological abnormalities, compared with admission of iodize oil later in pregnancy or treatment after birth. The disadvantages of iodize oil is an uneven level of iodine in the body over time and the need for direct contact with individuals with the accompanying increased costs.[4]
Iodine can be also given as KI or KIO3 drops or tablets. An oral dose of potassium iodide monthly is about 30 mg or biweekly is about 8 mg, which can provide adequate iodine for school-age children. Lugol's iodine provide ≈6 mg of iodine per drop, and similar preparations are also available as antiseptics in rural dispensaries in developing countries which is another simple way to deliver iodine locally. In IDD counters or weak salt iodization implementation, iodine supplement should be given to pregnant women, lactating women and infants. [4]
