224 Introduction to Human Nutrition
organifi cation of iodide. The concentration of iodine
in the thyroid gland also affects the uptake of iodide
into the follicle, the ratio of T 3 to T 4 , and the rate
of release of these hormones into the circulation.
This process is also under hormonal control by the
hypothalamus of the brain, which produces thyroid-
releasing hormone, which then stimulates the pitu-
itary gland to secrete thyroid-stimulating hormone
(TSH), which, in turn, acts on the thyroid gland to
produce more thyroid hormones.
Almost all of the thyroid hormones released from
the thyroid are bound to transport proteins, mainly
thyroxine-binding globulin. The longer half-life of T 4
ensures that there is a reservoir for conversion to the
more active T 3 with a much shorter half-life of 1 day.
The deiodination of T 4 to T 3 takes place in extra-
thyroidal tissues (mainly the liver). Excretion of
iodine is predominantly in the urine.
Defi ciency symptoms
A defi ciency of iodine causes a wide spectrum of
disorders from mild goiter (a larger thyroid gland
than normal) to the most severe forms of endemic
congenital hypothyroidism (cretinism) (severe, irre-
versible mental, and growth retardation). Collectively,
these manifestations of iodine defi ciency are termed
iodine defi ciency disorders (IDDs) and symptoms
differ depending on the life stage at which iodine
defi ciency occurs. The most severe disorders (con-
genital hypothyroidism) arise if the fetus suffers from
iodine defi ciency. The clinical features of endemic
congenital hypothyroidism are either a predominant
neurological syndrome with severe to profound
mental retardation, including defects of hearing and
speech (often deaf–mutism), squint, and disorders of
stance and gait of varying degrees (neurological con-
genital hypothyroidism), or predominant features of
hypothyroidism and stunted growth with less severe
mental retardation (myxedematous congenital hypo-
thyroidism). Profound hypothyroidism is biochemi-
cally defi ned as high serum TSH and very low T 4 and
T 3 , and is accompanied by a low basal metabolic rate,
apathy, slow refl ex relaxation time with slow move-
ments, cold intolerance, and myxedema (skin and
subcutaneous tissue are thickened because of an accu-
mulation of mucin, and become dry and swollen).
Although congenital hypothyroidism is the severest
form of IDD, varying degrees of intellectual or growth
retardation are apparent when iodine defi ciency
occurs in the fetus, infancy or childhood and adoles-
cence. In adulthood, the consequences of iodine defi -
ciency are more serious in women, especially during
pregnancy, than in men.
The mildest form of IDD, goiters, range from those
only detectable by touch (palpation) to very large
goiters that can cause breathing problems. The enlarge-
ment of the thyroid gland to produce goiter arises from
stimulation of the thyroid cells by TSH and, without
the ability to increase hormone production owing to
iodine defi ciency, the gland becomes hyperplastic.
Apart from congenital hypothyroidism, hypothy-
roidism, and goiter, other features linked to IDDs are
decreased fertility rates, increased stillbirth and spon-
taneous abortion rates, and increased perinatal and
infant mortality. The public health signifi cance of
iodine defi ciency cannot be underestimated, with
over 1 billion people (worldwide, but mostly in Asia
and Africa) estimated to be living in iodine-defi cient
areas and, therefore, at risk of IDDs. Estimates of
those with IDDs demonstrate the scale of the problem,
with 200–300 million goitrous people, over 40 million
affected by some degree of mental impairment and
some 7 million people with congenital hypothyroid-
ism. Fortunately, these fi gures should decrease as
public health programs using preventive interven-
tions with iodized oil (oral or intramuscular injec-
tion) salt, bread, water, or even sugar have an impact.
Treatment with iodine supplementation in older chil-
dren and adults can reverse many of the clinical mani-
festations of IDDs, including mental defi ciency,
hypothyroidism and goiter. Although iodine defi -
ciency is the primary cause of IDDs, goitrogenic
factors limiting bioavailability appear to be superim-
posed on the primary cause. In addition, genetic
variation, immunological factors, sex, age, and growth
factors seem to modify expression of the conditions,
producing a wide range of symptoms and severity of
IDDs with similar iodine intakes.Toxicity
A wide range of iodine intakes is tolerated by most
individuals, owing to the ability of the thyroid to
regulate total body iodine. Over 2 mg iodine/day for
long periods should be regarded as excessive or poten-
tially harmful to most people. Such high intakes are
unlikely to arise from natural foods, except for diets
that are very high in seafood and/or seaweed or com-
prising foods contaminated with iodine. In contrast