the follicular cells.

Each follicle is surrounded by basement membrane, between the follicles are the
parafollicular cells containing the calcitonin-secreting C cells.
Te metabolism of virtually all nucleated cells of most
tissues is controlled by the thyroid hormones. Te thyroid
synthesizes two hormones: (1) Triiodothyronine (T3), which
is the active hormone that acts at the cellular level and (2)
L-thyroxine (T4), which is the prohormone. Iodine is an essential requirement for thyroid hormone synthesis.
Inorganic
iodide (obtained from dietary sources) is trapped by the gland
by an enzyme-dependent system, oxidized, and incorporated into the glycoprotein thyroglobulin to form mono-
and
diiodotyrosine and then T4 and T3. Globally, dietary iodine
defciency is a major cause of thyroid disease. Te recommended daily intake of iodine is at least 140 µg. Dietary
supplementation of salt and bread has limited the regions where
endemic goiter still occurs, but surprisingly, iodine defciency
is again a concern in Western countries, because adventitious
iodine in dairy products is declining, with noniodoform disinfectants used in milk production, and non-iodized
rock salt
in place of iodized salt in cooking has become popular. In the
US, iodine intakes have fallen, and it is uncertain that the iodine status for most pregnant woman is satisfactory,
leading to
calls for systematic iodine supplementation.41,42
Hypothyroidism
Underactivity of the thyroid gland is usually primary, but can
be secondary to diseases of the hypothalamic-pituitary axis,
resulting in reduced TSH production and/or release. Hypothyroidism is one of the commonest endocrine
disorders.
Hypothyroidism can be either subclinical, or overt, with one
large US population-based survey fnding the prevalence
of subclinical disease to be 4.3% and that of overt disease
0.3%.43 Te overall UK prevalence for primary hypothyroidism is over 2% in women, but under 0.1% in men.
Lifetime
prevalence for an individual is higher, perhaps as high as 9%
for women and 1% for men, with a mean age at diagnosis
around 60 years. Te worldwide prevalence of subclinical
hypothyroidism varies from 1% to 10%.
TSH levels can usually accurately discriminate between
hyperthyroidism, hypothyroidism, and euthyroidism (normal thyroid gland function). Exceptions are
hypopituitarism
and “sick euthyroid” syndrome when low levels (which normally imply hyperthyroidism) occur in the presence
of low
or normal T4 and T3 levels. As a single test of thyroid function TSH is sufciently sensitive in most
circumstances, but
for an accurate diagnosis of hypothyroidism, TSH plus the
serum free T4 levels should be tested. When hyperthyroidism is suspected, the TSH as well as the free T4 and
free T3
need to be checked.
Antithyroid antibodies are common and may be destructive or stimulating or both. Destructive antibodies are
directed against the microsomes or against the thyroglobulin.
Te antigen for thyroid microsomal antibodies is the thyroid
peroxidase (TPO) enzyme. TPO antibodies are found in up
to 20% of the normal population, especially older women,
but only 10–20% of these develop overt hypothyroidism.
TSH receptor IgG antibodies (TRAb) typically stimulate,
but occasionally block, the receptor.
Primary Hypothyroidism: Etiology
Atrophic (autoimmune) hypothyroidism is the most common cause of hypothyroidism. Te pathophysiology
involves
the development of antithyroid autoantibodies, leading to
lymphoid infltration of the gland and eventual atrophy
and fbrosis. It is far more common in women (with a 6:1
female-to-male ratio), and the incidence increases with age.
Te condition is associated with other autoimmune disease
such as pernicious anemia, vitiligo, and other endocrinopathies. Hashimoto’s thyroiditis is another form of
autoimmune
thyroiditis, more common in women and most commonly
presenting in late middle age, that produces atrophic changes
with regeneration, leading to goiter formation. TPO antibodies are present, often in very high titers (>1000
IU/L),
and patients can be hypothyroid or euthyroid, although they
may go through an initial toxic phase. Postpartum thyroiditis
is usually a transient phenomenon following pregnancy, but
such postpartum thyroiditis may be misdiagnosed as postnatal depression, emphasizing the need for thyroid
function
tests in this context.
Dietary defciency of iodine is still common and in some
areas endemic goiter is still a frequent occurrence. Efforts
to prevent defciency by providing iodine in salt continue
worldwide, but often with incomplete success. In India some
500 million have iodine defciency and about 2 million have
cretinism. Cretinism (the preferred term is congenital hypothyroidism) is a condition of severely impaired
physical and
mental development and growth due to untreated congenital
defciency of the thyroid hormones. Te most common cause
is maternal hypothyroidism, which occurs as a consequence
of dietary defciency of iodine. It has affected many people
worldwide and continues to be a major public health problem in many countries. Iodine defciency remains the
most
common preventable cause of intellectual impairment and
disability worldwide.44
Hypothyroidism may also result from the loss of
the TSH-producing cells of the pituitary gland (secondary hypothyroidism). Although less common, it can be
caused indirectly by a large, nonfunctioning pituitary
adenoma.
Clinical Features
Hypothyroidism produces many symptoms. Te alternative
term myxoedema refers to the accumulation of mucopolysaccharide in the subcutaneous tissues. Te hypothyroid
patient is the mirror image of the hyperthyroid patient.73
Patients are chronically fatigued, cold when others are comfortable, gaining weight without eating more,
constipated,
and bradycardic, with slowed reflexes. A slowed relaxation
phase of the Achilles tendon reflex is an accurate physical