**2. Risk factors for thyrotoxicosis following an iodine load**

#### **2.1 Normal adaptation to iodine intake**

Thyroid hormone secretion is regulated by two mechanisms: a central hypothalamic-pituitary and a local autoregulatory mechanism depending on the iodine content of the gland. The autoregulatory mechanism reduces the fluctuation of thyroid hormone secretion in the event of sudden changes in iodine supply. Iodine excess inhibits iodide accumulation, organogenesis, tyrosine binding, and thyroid hormone release. However, this inhibitory effect (Wolff-Chaikoff effect) lasts only 10–14 days, followed by the so-called escape phenomenon [6].

Iodine is a micronutrient that is present in foods (e.g., seaweed, seafood, dairyand grain products, eggs), added to processed foods as iodized salt, and available as a dietary supplement, but the iodine concentration of water and foods is highly variable. Studies of iodine balance, based on the assumption that a healthy subject on an adequate diet maintains equilibrium between iodine intake and losses, have provided highly variable results, thus, cannot be used for setting daily reference values [7]. When iodine losses exceed intake (negative balance), deposits are progressively depleted resulting in biological signs and in clinical symptoms of deficiency. The physiological response to iodine deficiency is the preferential synthesis of T3 instead of T4. Long-term follow-up suggests that chronic iodine deficiency may lead to insufficient thyroid function (hypothyroidism) associated with a compensatory thyroid hypertrophy/hyperplasia with goiter (enlarged thyroid gland). Myxedema, observed with severe iodine deficiency, also results from hormone deficiency and is associated with reduced metabolic rate, weight gain, swollen face, edemas, hypothermia, and mental slowness. In euthyroid subjects, the plasma concentration of iodine (inorganic and organic iodine) ranged from 40 to 80 μg/L. Concentrations between 80 and 250 μg/L are associated with hyperthyroidism, whereas concentrations above 250 μg/L usually result from iodine overload with iodinated drugs [8, 9]. The thyroid gland, being highly flexible, is able to concentrate iodine up to 80-fold, and in most healthy adults, no clinical signs will appear at an iodine intake of up to 2 g/day [10]. However, if the adaptation to high iodine intake fails, various diseases occur. Chronic excessive iodine supply can also lead to goiter [11] and may accelerate the development of subclinical thyroid disorders to overt hypothyroidism or hyperthyroidism, increase the incidence of autoimmune thyroiditis, and increase the risk of thyroid cancer [10, 12, 13]. Recently, high iodine intake (exceeding 160 μg daily) was suggested as a risk factor for type 2 diabetes [14].

#### **2.2 Iodine-induced thyrotoxicosis mechanisms**

Iodine-induced hyperthyroidism (thyrotoxicosis) or Jod-Basedow effect is most frequently observed following iodine supplementation in individuals who had previously experienced severe iodine deficiency [15, 16]. A plausible explanation of this phenomenon can be the thyroid stimulating hormone (TSH) hyperstimulation of the thyroid gland, which may occur as an adaptive response to the iodinedeficient conditions and results in autonomous growth and function of thyrocyte

**61**

**3.2 Dietary supplements**

*Prevention and Treatment of Iodine-Induced Thyrotoxicosis*

clusters. When iodine intake increases, these nodules may synthesize an excessive amount of thyroid hormones [10]. The mechanism consists of escape phenomenon when high doses of iodine are used for thyroid hormone synthesis, which can lead to severe thyrotoxicosis. The high iodine containing amiodarone and its metabolite N-desethylamiodarone (DEA) affects T cell function by increasing the number of both helper and cytotoxic T lymphocytes and induces destructive thyroiditis, resulting in transient thyrotoxicosis, as suggested by clinical, histological, and

High levels of organic iodide (thyroid hormones) also reduce the accumulation

The effects of iodine administration differ in patients with pre-existing thyroid pathology from those in healthy subjects and depend upon the underlying disease

**3. Major sources of increased iodine exposure: iodine supplementation, dietary iodine, iodine-containing contrast media, amiodarone, and** 

The assessment of iodine deficiency can be accomplished by assessing the prevalence and severity of goiter, by testing the excretion of iodine in urine, and by determining hormonal levels (e.g., TSH, FT4). When used alone, neither of these are sufficiently sensitive and specific to measure iodine deficiency of a population, but urinary iodine remains the index of choice in the monitoring of iodine supplementation programmes. The most successful method of intervention for iodine deficiency control is salt iodization, iodine being added to salt as potassium iodide (KI), potassium iodate (KIO3), or sodium iodide (NaI). Due to the high prevalence of hypertension and cardiovascular diseases, many countries proposed to promote the reduction of salt intake to 5 g/day (<2 g of sodium), so complementary measures are needed in order to tackle iodine deficiency [20]. But iodine also binds to fatty acids, so iodine oil can also be given orally or intravenously to severely iodine-deficient patients in the short term. Nascent iodine is like the precursor form of iodine, which converts into thyroid hormones. The human body can recognize and assimilate this form more easily than potassium salt. Lugol's solution is a widely used commercial iodine source, which contains elemental iodine and potassium iodide also. If someone consumes high quantities of iodine-rich foods (e.g., marine food, kelp), the use of iodized salt or iodinated water may increase iodine levels above the safe upper level as recommended by WHO. Individuals, who consume large amounts of seaweed regularly, are also exposed to the risk of iodine-induced hyperthyroidism [21, 22]. Several reports are available describing diet-induced thyrotoxicosis in patients consuming seaweed-containing foods or beverages [23]. Risk factors for iodineinduced hyperthyroidism include nontoxic or diffuse nodular

**the clinical forms of amiodarone-induced thyrotoxicosis**

goiter, latent Graves' disease, and long-standing iodine deficiency [24].

Most dietary supplements, as well as food and water, contains iodine as salts: sodium iodide, sodium iodate, potassium iodide, and potassium iodate. Different solid dosage forms of potassium iodide are available, but around 20% is assimilated from inorganic forms of iodine into the body [25]. Iodine is also present in most multivitamin/mineral supplements. Some case reports described that previously

of iodide ions in the thyroid gland inhibiting the TSH secretion.

*DOI: http://dx.doi.org/10.5772/intechopen.89615*

in vitro studies [17–19].

**3.1 Iodine supplementation**

process.

*Prevention and Treatment of Iodine-Induced Thyrotoxicosis DOI: http://dx.doi.org/10.5772/intechopen.89615*

*Goiter - Causes and Treatment*

women lowers thyroid hormone level [5].

**2.1 Normal adaptation to iodine intake**

gested as a risk factor for type 2 diabetes [14].

**2.2 Iodine-induced thyrotoxicosis mechanisms**

pregnant women confirmed that iodine intake in this population of Romania is insufficient [2]. Administration of supplemental iodine to subjects with iodine deficiency goiter can result in iodine-induced hyperthyroidism in nonpregnant persons [4], but iodine supplementation in mild and moderate iodine-deficient pregnant

Thyroid hormone secretion is regulated by two mechanisms: a central hypothalamic-pituitary and a local autoregulatory mechanism depending on the iodine content of the gland. The autoregulatory mechanism reduces the fluctuation of thyroid hormone secretion in the event of sudden changes in iodine supply. Iodine excess inhibits iodide accumulation, organogenesis, tyrosine binding, and thyroid hormone release. However, this inhibitory effect (Wolff-Chaikoff effect) lasts only

Iodine is a micronutrient that is present in foods (e.g., seaweed, seafood, dairyand grain products, eggs), added to processed foods as iodized salt, and available as a dietary supplement, but the iodine concentration of water and foods is highly variable. Studies of iodine balance, based on the assumption that a healthy subject on an adequate diet maintains equilibrium between iodine intake and losses, have provided highly variable results, thus, cannot be used for setting daily reference values [7]. When iodine losses exceed intake (negative balance), deposits are progressively depleted resulting in biological signs and in clinical symptoms of deficiency. The physiological response to iodine deficiency is the preferential synthesis of T3 instead of T4. Long-term follow-up suggests that chronic iodine deficiency may lead to insufficient thyroid function (hypothyroidism) associated with a compensatory thyroid hypertrophy/hyperplasia with goiter (enlarged thyroid gland). Myxedema, observed with severe iodine deficiency, also results from hormone deficiency and is associated with reduced metabolic rate, weight gain, swollen face, edemas, hypothermia, and mental slowness. In euthyroid subjects, the plasma concentration of iodine (inorganic and organic iodine) ranged from 40 to 80 μg/L. Concentrations between 80 and 250 μg/L are associated with hyperthyroidism, whereas concentrations above 250 μg/L usually result from iodine overload with iodinated drugs [8, 9]. The thyroid gland, being highly flexible, is able to concentrate iodine up to 80-fold, and in most healthy adults, no clinical signs will appear at an iodine intake of up to 2 g/day [10]. However, if the adaptation to high iodine intake fails, various diseases occur. Chronic excessive iodine supply can also lead to goiter [11] and may accelerate the development of subclinical thyroid disorders to overt hypothyroidism or hyperthyroidism, increase the incidence of autoimmune thyroiditis, and increase the risk of thyroid cancer [10, 12, 13]. Recently, high iodine intake (exceeding 160 μg daily) was sug-

Iodine-induced hyperthyroidism (thyrotoxicosis) or Jod-Basedow effect is most

frequently observed following iodine supplementation in individuals who had previously experienced severe iodine deficiency [15, 16]. A plausible explanation of this phenomenon can be the thyroid stimulating hormone (TSH) hyperstimulation of the thyroid gland, which may occur as an adaptive response to the iodinedeficient conditions and results in autonomous growth and function of thyrocyte

**2. Risk factors for thyrotoxicosis following an iodine load**

10–14 days, followed by the so-called escape phenomenon [6].

**60**

clusters. When iodine intake increases, these nodules may synthesize an excessive amount of thyroid hormones [10]. The mechanism consists of escape phenomenon when high doses of iodine are used for thyroid hormone synthesis, which can lead to severe thyrotoxicosis. The high iodine containing amiodarone and its metabolite N-desethylamiodarone (DEA) affects T cell function by increasing the number of both helper and cytotoxic T lymphocytes and induces destructive thyroiditis, resulting in transient thyrotoxicosis, as suggested by clinical, histological, and in vitro studies [17–19].

High levels of organic iodide (thyroid hormones) also reduce the accumulation of iodide ions in the thyroid gland inhibiting the TSH secretion.

The effects of iodine administration differ in patients with pre-existing thyroid pathology from those in healthy subjects and depend upon the underlying disease process.
