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ficient (hypothyroid) state, the BMR can fall to 2025 kcal/ m2/hr, whereas in instances of hormone excess (thyrotoxicosis or hyperthyroidism) it may rise as high as 60-65 kcal/m2/hr.

B. Iodine Metabolism

The principal hormones produced by the thyroid are thyroxine (T4) and triiodothyronine (T3), which contain, respectively, four and three atoms of organically bound iodine (see Section III). Accordingly, the normal functioning of the thyroid is dependent upon adequate and regular dietary intake of iodine.

Iodine is a rare element; although it is present in ocean water, it is distributed unevenly in the soils of the various land masses of the world. For adults the recommended daily allowance (RDA) of iodine established by the U.S. National Research Council is 150 fig/day. In the United States, the average daily intake of iodine by adults is in the range of 250700 fjig/day, largely as iodide. The main dietary sources of iodine are iodized salt and iodate, which is used as a bread preservative. Present-day iodized salt contains 100 mg of Kl/kg of salt (0.01% KI).

In the absence of adequate dietary access to iodine, an individual will adaptively develop iodine deficiency or endemic goiter. The definition of endemic goiter can be described in statistical terms and exists when 10-20% or more of preadolescent children in a given geographic or population grouping have enlarged, mildly hypertrophied thyroid glands. In most adults with endemic goiter, iodine intake will be below 50-75 /¿g/day and urinary excretion can fall to 20-50 /¿g/day. Endemic goiter does not exist in the United States. However, endemic goiter can be found in areas of the world in which there is a suboptimal level of iodine in the soil and in food crops grown thereon, e.g., large areas of central Africa, central Asia, the Andes of South America, and Indonesia. It has been clearly demonstrated that endemic goiter can be prevented by the oral administration of potassium iodide at 6-month intervals.

C. Metabolic Effects of Thyroid Hormones

The thyroid hormones, depending upon whether they are present at elevated or reduced levels, have a wide range of effects in humans that are evident at many different levels of organization; these effects range from behavioral changes, growth effects, changes in cardiac output, gastrointestinal function, and tissue oxygen consumption, muscle myopathy

(weakness), to perturbations of the immune mechanism.

In instances of thyroid hormone excess, the subject has an accelerated BMR and an elevated cardiac output associated with high body temperature, warm skin, and inappropriate sweating for the ambient temperature. Because the muscle mass of the body constitutes 50% of body weight, and because muscle tissue has a high rate of oxygen consumption, the increased muscular metabolic activity substantially contributes to the higher BMR. Although hyperthyroid subjects often increase their food intake, there is usually a concomitant weight loss related to the greater gastrointestinal activity and associated diarrhea. Such an individual is often hyperactive, with rapid movements and exaggerated reflexes, and often exhibits short attention spans. The muscle myopathy is attributable to both abnormal protein catabolism with negative nitrogen balance and abnormal neuromuscular transmission. A prominent external physical feature of hyperthyroidism is exophthalmos or bulging of the eyeball.

In many respects, the symptoms of a hypothyroid subject are the inverse of these described earlier for thyroid hormone excess. The BMR is reduced, with an associated enlarged heart that has reduced cardiac output. Accordingly, the body temperature is lowered, the skin is "cool," and sweating is reduced in relation to the ambient temperature. Also, the hypothyroid's appetite is poor and there is reduced gastrointestinal activity. Although the skeletal muscles are somewhat enlarged, there is an obvious myopathy. The principal external clinical features of hypothyroidism include a "myexdemic appearance." This describes the accumulation under the skin of mucoproteins and fluids, which result in the subject having a "puffy" appearance as a consequence of alterations in electrolyte and water balances.

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