Chapter 528

Hypothyroidism can develop at any age among previously healthy children, although it is more common among girls. Growth retardation is an early sign. Iodine deficiency remains a major cause of hypothyroidism, but the worldwide incidence is decreasing. A high proportion of patients have circulating antithyroid antibodies characterizing an autoimmune process (Hashimoto thyroiditis). Among others, acquired juvenile hypothyroidism can be caused by exposure to goitrogenic agents, thyroid dysgenesis, late onset of hypothyroidism caused by an inborn error of thyroidal biosynthesis, acquired hypothalamic or pituitary hypothyroidism, or endemic factors.1-6 As part of the clinical history, the physician should inquire about potential intake, or contact through environmental or familial occupational” sources, with the known potential goitrogens listed in Table 527-2.

Iodine deficiency remains the leading cause of hypothyroidism worldwide.7-16 During the past 40 years, major efforts to supplement iodine intake in endemic deficiency areas have been highly successful, and the geographic distribution of severe endemic iodine deficiency has been markedly reduced. Residual areas of deficiency include Africa; Southeast Asia; the Western Pacific; and some areas of Europe, the Eastern Mediterranean, and the more isolated mountainous areas of the Americas. It is estimated that some 2 billion individuals remain at risk, with 740 million affected by iodine-deficient goiter and 43 million believed to be mentally disabled as the result of iodine deficiency.16

In Europe from 1989 to 1995, clinically euthyroid schoolchildren in iodine-deficient areas were reported to have subtle or overt neuropsychointellectual deficits compared to iodine-sufficient children in the same areas. This is believed to result from transient hypothyroidism during the critical fetal-postnatal period of brain development. Similar studies have not been conducted in the Americas. Cretinism and severe iodine deficiency are now largely restricted to remote areas of developing countries. However, some 40 million individuals in the Americas and 130 million in Europe are exposed to mild-moderate iodine deficiency, largely in more isolated mountainous areas.

Environmental iodine deficiency leads to a series of thyroid system abnormalities, including increased thyroid-stimulating hormone (TSH) secretion, increased iodide uptake, reduced thyroglobulin iodination, increased thyroglobulin production and turnover, thyroid colloid depletion, and thyroid gland hypertrophy and hyperplasia.16Iodine deficiency results in poorly iodinated tyrosine and iodothyronine residueswithin stored thyroglobulin, resulting in increased (MIT/DIT) and T3/T4 ratios. As a result, the thyroid T3/T4 secretion ratio is increased and serum T3 levels are relatively increased while serum T4 concentrations fall. T4-to-T3 conversion within the thyroid gland and in peripheral tissues also increases. The result of these changes is a circumstance of compensated euthyroidism manifest by a modest increase in serum TSH, a high normal or increased serum T3 level, a low normal or decreased serum T4 concentration, and thyroidal hyperplasia and hyperactivity.

The increased T3/T4 secretion ratio allows a degree of adaptation to iodine deficiency because T3 possesses four times the metabolic potency ...

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