The Endocrine System
341
Thus, circulating antibodies are produced that bind to and
activate the TSH receptor. The thyroid gland responds
to these antibodies as if TSH itself were binding to the
receptor. This response causes hypertrophy of the thyroid
and increased TH production, because there is no way
for thyroid hormones to turn off antibody production by
negative feedback. T
3
and T
4
do, however, feed back on the
hypothalamus and pituitary gland, as usual. Thus, Graves’
disease is characterized by elevated thyroid hormone levels
despite suppressed TSH. The hypertrophy produced by
the constant stimulation of the gland results in a goiter.
This is an important point: The presence of a goiter in and
of itself does not distinguish between hypothyroidism and
hyperthyroidism, because both types of disease can result in
thyroid hypertrophy.
The signs and symptoms of thyrotoxicosis can be
predicted in part from the previous discussion about
hypothyroidism. Hyperthyroid patients tend to have
heat
intolerance,
weight loss, increased appetite, and often
show signs of increased sympathetic nervous system activity
(anxiety, tremors, jumpiness, increased heart rate).
Hyperthyroidism can be very serious, particularly
because of its effects on the cardiovascular system (largely
secondary to its permissive actions on catecholamines). It may
be treated with drugs that inhibit thyroid hormone synthesis,
by surgical removal of the thyroid gland, or by destroying a
portion of the thyroid using radioactive iodine. In the last
case, the radioactive iodine is ingested. Because the thyroid
is the chief region of iodine uptake in the body, most of the
radioactivity appears within the gland, where its high-energy
gamma rays partly destroy the tissue. Following treatment,
patients may need to take thyroid replacement pills each day
to maintain their TSH and T
3
/T
4
levels, unless suffi cient
functional thyroid tissue remains after radiotherapy.
SECTION C SUMMARY
Synthesis of Thyroid Hormones
I. T
3
and T
4
are synthesized by sequential iodinations of
thyroglobulin in the thyroid follicle lumen, or colloid. Iodinated
tyrosines on thyroglobulin are coupled to produce either T
3
or T
4
.
II. The enzyme responsible for T
3
/T
4
synthesis is thyroid peroxidase.
Control of Thyroid Function
I. All of the synthetic steps involved in T
3
/T
4
synthesis are
stimulated by TSH. TSH also stimulates uptake of iodide,
where it is trapped in the follicle.
II. TSH causes growth (hypertrophy) of thyroid tissue. Excessive
exposure of the thyroid to TSH can cause goiter.
Actions of Thyroid Hormones
I. T
3
/T
4
increase the metabolic rate, and thus promote
consumption of calories (calorigenic effect). This results in
heat production.
II. The actions of the sympathetic nervous system are potentiated
by T
3
/T
4
. This is called the permissive action of T
3
/T
4
.
III. Thyroid hormones are essential for normal growth and
development—particularly of the nervous system—during fetal
life and childhood.
Additional Clinical Examples
I. Hypothyroidism most commonly results from autoimmune
destruction of all or part of the thyroid. It is characterized by
weight gain, fatigue, cold intolerance, and changes in skin tone
and mentation. It may also result in goiter.
II. Hyperthyroidism is also typically the result of an autoimmune
disorder. It is characterized by weight loss, heat intolerance,
irritability and anxiety, and often goiter.
calorigenic
339
colloid
337
diiodotyrosine (DIT)
337
follicle
337
hypertrophy
338
iodide trapping
337
iodine
337
monoiodotyrosine (MIT)
337
thyroglobulin
337
thyroid peroxidase
337
thyroxine (T
4
)
337
triiodothyronine (T
3
)
337
SECTION C CLINICAL TERMS
autoimmune thyroiditis
340
cold intolerance
340
cretinism
339
goiter
338
Graves’ disease
340
Hashimoto’s disease
340
heat intolerance
341
hyperthyroidism
340
hypothyroidism
340
myxedema
340
thyrotoxicosis
340
SECTION C REVIEW QUESTIONS
1. Describe the steps leading to T
3
and T
4
production, beginning
with the transport of iodide into the thyroid follicular cell.
2. What are the major actions of TSH on thyroid function and
growth?
3. What is the major way in which the TRH/TSH/TH pathway
is regulated?
4. Explain why the symptoms of hyperthyroidism may be
confused with a disorder of the autonomic nervous system.
5. Explain how both hypothyroidism and hyperthyroidism can
result in the appearance of a goiter.
SECTION C KEY TERMS
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