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