Source: Medicines Authority (MT) Revision Year: 2019 Publisher: BIAL – Portela & Cª, S.AÀ Av. da Siderurgia Nacional, 4745-457 S. Mamede do Coronado, Portugal
Pharmacotherapeutic group: iodotherapy
ATC code: H03CA
The main effects of iodine in humans have been characterized in experimental studies, clinical and epidemiological studies conducted in humans. Far from it, there are few useful animal models to demonstrate these mechanisms of action.
Iodine is an essential element for the synthesis of thyroid hormones, thyroxin (T4) and triiodothyronine (T3), constituting 65% and 59% of their molecular weights, respectively. Thyroid hormones have an important role in the metabolism of most cells, and in the initiation of growth and development of most organs, especially the brain that occurs during early foetal and postnatal age.
Iodine is not only the major substrate of the thyroid gland to synthesize thyroid hormones, but also influences directly on specific thyroid functions as well as cell proliferation. The daily intake of iodine in areas without deficiency ranges between 50 to 1000 micrograms daily and thyroid function remains normal, without changes in thyroid stimulating hormone (TSH). This phenomenon is explained by the presence of a self-regulation process, that is, the ability of the thyroid to regulate their own function and growth, depending on the availability of intrathyroidal iodine and the modulation of response to thyrotrophic factors.
Iodine acts as an endocrine modifier whose main direct outcomes in case of excessive iodine intake occur in the thyroid gland and on the regulation of production and secretion of thyroid hormones.
The iodine content of the thyroid gland is related generally to the intake of iodine. In those situations where iodine supplements have been abundant, the thyroid may contain 10-20 mg, but in situations of chronic iodine deficiency the thyroid may contain only quantities of 200 micrograms.
Therefore, a sufficiently severe iodine deficiency can affect thyroid hormone synthesis during this critical period and cause hypothyroidism and brain damage. The clinic consequence will be a mental retardation.
The anti-goitrogenic effect of potassium iodide is due to inhibition of thyroid protein biosynthesis. The effect is specific to the thyroid gland.
The effects of severe iodine deficiency on neurological development are well documented. Iodine is an essential element in the synthesis of T3 and T4 and that neurological sequelae owing to iodine deficiency are mediated by thyroid hormone deficiency, varying from a minimum effect on the brain function to a serious intellectual incapacity syndrome. In a meta-analysis published about neuromotor and cognitive functions in the presence of an iodine deficiency was conclusive that iodine deficiency entails a loss of 13-15 points in the intellectual coefficient in terms of the global population.
In a study carried out in a region of Papua New Guinea with serious iodine deficiency and they established the relationship between thyroid hormone levels during pregnancy and the consequent motor and cognitive performance of their children: the higher the iodine deficiency during pregnancy was, the lower the motor and cognitive performance of their children.
Another study carried out in Xinjiang by Cao et al. on pregnant women who were systematically administered iodine, revealed that treatment with iodine during the two first trimesters of pregnancy protects the brain of the foetus from the damages associated with the iodine deficiency and that, although treatment during the third trimester of pregnancy or after birth does not improve the neurological state of the children, it does slightly increase both cranial growth and the development coefficient thereof.
Another author studied the effects of iodine deficiency on mental and psychomotor skills in the population who did not show symptoms of cretinism, but who lived in an area with severe iodine deficiency where cretinism was an endemic illness. The author of the study observed that there was no major mental retardation in the non-cretin population group, whilst differences were observed between the two population groups (cretin and non-cretin) in terms of the number of perceptual or neuromotor skills or abilities.
Other authors have also studied the impact that iodine deficiency has on thyroid function in pregnancy and on the neonate, and the intellectual development of babies and children, state that the damage increases the greater the deficiency is, being endemic cretinism the most serious of the consequences. They also concluded that hypothyroxinemia during the start of pregnancy is a key factor in the development of neurological damage in the child affected by neurological cretinism and that iodine deficiency involves an overall loss of 10-15 points in terms of the intellectual coefficient, constituting one of the main preventable causes of brain damage and mental retardation.
Regarding safety of iodine intake, the World Health Organisation intakes up to 1000 µg of iodine per day are safe from a medical standpoint, presenting no problem to pregnant women and foetal development.
See section 4.2 for information on paediatric use.
Iodine is quickly absorbed, mainly in the small intestine.
Once absorbed is rapidly distributed across the extracellular fluid. Then it will be captured by thyroid cells as a substrate for thyroid hormones. Only 30 percent of the body’s iodine is concentrated in the thyroid tissue and thyroid hormones. The remaining nonhormonal iodine is found in a variety of tissues, including mammary tissue, eye, gastric mucosa, cervix, and salivary glands. Iodine crosses the placental barrier and is secreted in breast milk.
The main elimination is urinary and, lesser amount, faecal.
In animals, symptoms of acute iodine toxicity include diarrhea, alternating periods of hyperactivity, weakness, prostration, convulsions and death.
In sub-chronic toxicity studies there have been cases of weight gain and haemolysis. Also, it is postulated that the excess of iodine in the diet may promote autoimmune thyroiditis.
In a long term study where rats received potassium iodide in the drinking water for two years the development of squamous cell carcinomas in the salivary glands were observed. In a chronic toxicity study was identified a metaplasia manifestation. Both, iodine deficiency and an excess of it, may promote tumour formation in pre-treated animals with known carcinogens. The available data on genotoxicity suggest that stable iodine has no mutagenic potential.
The data of adverse effects on reproduction and foetal development are limited. A single high dose has been found to be teratogenic in rats. In another study in rats the administration of high daily iodine doses led to incomplete parturition, failure of lactation and reduced mothering activities. There are experimental studies that demonstrate the usefulness of potassium iodide to protect the foetal thyroid gland and to inhibit the transfer of radioactive iodine to milk.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
