fected by deranged thyroid function (Goodman 2003), making it among the most prevalent of endocrine diseases (Larsen et al. 2002). The prevalence of subclinical thyroid dysfunction in various populations is 1.3-17.5% for subclinical hypothyroidism and 0.6-16% for subclinical hyperthyroidism; the reported rates depend on age, sex, iodine intake, sensitivity of measurements, and definition used (Biondi et al. 2002). Normal thyroid function requires sufficient intake of iodine (at least 100 micrograms/day [µg/d]), and areas of endemic iodine deficiency are associated with disorders such as endemic goiter and cretinism (Larsen et al. 2002; Larsen and Davies 2002; Goodman 2003). Iodine intake in the United States (where iodine is added to table salt) is decreasing (CDC 2002d; Larsen et al. 2002), and an estimated 12% of the population has low concentrations of urinary iodine (Larsen et al. 2002).

The principal regulator of thyroid function is the pituitary hormone thyroid-stimulating hormone (TSH), which in turn is controlled by positive input from the hypothalamic hormone thyrotropin-releasing hormone (TRH) and by negative input from T4 and T3. TSH binds to G-protein-coupled receptors in the surface membranes of thyroid follicular cells (Goodman 2003), which leads to increases in both the cyclic adenosine monophosphate (cAMP) and diacylglycerol/inositol trisphosphate second messenger pathways (Goodman 2003). T3, rather than T4, probably is responsible for the feedback response for TSH production (Schneider et al. 2001). Some T3, the active form of thyroid hormone, is secreted directly by the thyroid along with T4, but most T3 is produced from T4 by one of two deiodinases (Types I and II1) in the peripheral tissue (Schneider et al. 2001; Larsen et al. 2002; Goodman 2003). T3 enters the nucleus of the target cells and binds to specific receptors, which activate specific genes.


An effect of fluoride exposure on the thyroid was first reported approximately 150 years ago (Maumené 1854, 1866; as cited in various reports). In 1923, the director of the Idaho Public Health Service, in a letter to the Surgeon General, reported enlarged thyroids in many children between the ages of 12 and 15 using city water in the village of Oakley, Idaho (Almond 1923); in addition, the children using city water had severe enamel deficiencies in their permanent teeth. The dental problems were eventually attributed to the presence in the city water of 6 mg/L fluoride, and children born after a change in water supply (to water with <0.5 mg/L fluoride) were not


Type I deiodinase, along with Type III, is also responsible for deactivating T4 and T3 by removing the iodine atoms (Schneider et al. 2001; Larsen et al. 2002; Goodman 2003).

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