340
Chapter 11
Figure 11–24
Goiter at an advanced stage.
Because thyroid diseases are among the most common of all
endocrine diseases, it is worth describing in detail the causes
and symptoms of hyposecretion of TH (hypothyroidism) and
hypersecretion of TH (hyperthyroidism).
Hypothyroidism and Hyperthyroidism
Any condition characterized by plasma levels of TH that are
chronically below normal is known as
hypothyroidism
.
Most
cases of hypothyroidism—about 95 percent—are primary
defects resulting from damage to or loss of functional thyroid
tissue, or to inadequate iodine consumption.
One form of hypothyroidism that exists around the
world is caused by iodine defi ciency. In such cases, the
synthesis of TH is compromised, leading to a decrease
in the plasma levels of those hormones. This, in turn,
releases negative feedback on the hypothalamus and
pituitary, and TRH levels become chronically elevated in
the portal circulation of the anterior pituitary. Plasma TSH
concentration is also elevated due to the increased TRH.
The resulting overstimulation of the thyroid can produce
goiters that can achieve astounding sizes if untreated
(
Figure 11–24
). This form of hypothyroidism is reversible
if iodine is added to the diet. It is extremely rare in the
United States because of the widespread use of iodized salt,
in which one in every 10,000 molecules of NaCl is replaced
with NaI.
The most common cause of hypothyroidism in the
U.S. is due to autoimmune destruction of the thyroid
ADDITIONAL CLINICAL EXAMPLES
gland
(
autoimmune thyroiditis
).
One such situation is
Hashimoto’s disease,
in which cells of the immune system
called T-cells attack and destroy thyroid tissue. Like many
other autoimmune diseases, Hashimoto’s disease is more
common in women and can slowly progress with age. As
thyroid hormones begin to decrease, TSH levels increase due
to the decreased negative feedback, and a goiter can develop.
The usual treatment for autoimmune thyroiditis is daily
replacement with pharmaceutical preparations of T
4
. This
restores the thyroid hormone levels in the blood and causes
the TSH levels to decrease to normal.
The signs and symptoms of hypothyroidism in adults
may be mild or severe, depending on the degree of hormone
defi ciency. These include an increased sensitivity to cold
(
cold intolerance
)
and a tendency toward weight gain. Both
of these symptoms are related to the decreased calorigenic
actions normally produced by thyroid hormone. Many of the
other symptoms appear to be diffuse and nonspecifi c, such as
fatigue, changes in skin tone, hair, appetite, gastrointestinal
function, and mental function (decreased concentration). The
basis of the last effect is uncertain, but it has been postulated
to be related in part to a decrease in cerebral blood fl ow,
which in turn may be secondary to a decrease in the pumping
activity of the heart. Recall that thyroid hormones are
permissive for the actions of epinephrine and norepinephrine,
and that these two catecholamines are responsible in part for
maintaining normal cardiac function.
In severe, untreated hypothyroidism, certain hydrophilic
polymers called glycosaminoglycans accumulate in the
interstitial space in scattered regions of the body. Normally,
thyroid hormones act to prevent overexpression of these
extracellular compounds that are secreted by connective tissue
cells. In the absence of TH, therefore, these hydrophilic
molecules accumulate, and water tends to be trapped with
them. This combination causes a characteristic puffi ness of
the face and other regions that is known as
myxedema
.
As in the case of hypothyroidism, there are a variety
of ways in which
hyperthyroidism,
or
thyrotoxicosis,
can
develop. Among these are hormone-secreting tumors of
the thyroid (very rare), but the most common form of
hyperthyroidism is an autoimmune disease called
Graves’
disease
.
Like Hashimoto’s disease, Graves’ disease is
more common in women and may have a gradual onset,
typically beginning between the ages of 20 and 40.
The plasma of patients with Graves’ disease contains
antibodies that recognize the TSH receptor. Unlike
other autoimmune diseases in which a receptor protein
is attacked (e.g., myasthenia gravis, Chapter 9), the anti-
TSH receptor antibodies actually stimulate the receptor.
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