686
Chapter 19
Why is the serum glucose sample obtained in the
fasted state (see Figure 16–8)? Does the serum glucose
concentration rule out diabetes mellitus as a factor in
this patient’s illness?
Diagnosis
The most likely explanation for the fi ndings is an increase in
thyroid hormone in the patient’s blood. When elevated thyroid
hormone causes signifi cant symptoms, it is part of a condition
called
hyperthyroidism,
which, when severe enough, can lead
to
thyrotoxicosis.
The enlarged organ in the neck is likely the
thyroid gland, although large thyroid glands (
goiters
) also oc-
cur in hypothyroidism (see Figure 11–24 for an extreme ex-
ample). In order to interpret the thyroid function tests shown
in Table 19–1, fi rst review the control of thyroid hormone syn-
thesis and release (see Figure 11–23).
There are two circulating thyroid hormones—thyroxine
(T
4
) and triiodothyronine (T
3
). Whereas T
4
is the principal
hormone released by the thyroid gland, T
3
is actually more po-
tent and is actively produced in target tissues by the removal of
one iodine molecule from T
4
. The release of T
4
by the thyroid
gland is normally controlled by thyroid-stimulating hormone
(TSH) secreted by the anterior pituitary gland. Binding of
TSH to its G-protein-coupled plasma membrane receptor acti-
vates adenylyl cyclase and cAMP formation, which then stim-
ulates cAMP-dependent protein kinase (see Figure 5–6). Like
most anterior pituitary tropic/trophic hormones, TSH not
only stimulates the activity of the thyroid gland, it also stimu-
lates its growth. As with most other pituitary-target hormone
systems, the target gland hormone (T
4
) inhibits the release
of the anterior pituitary hormone controlling it (in this case,
TSH) via negative feedback (see Figures 11–20 and 11–23).
There are several reasons why the thyroid gland in this
patient could be producing too much thyroid hormone, lead-
ing to thyrotoxicosis. The most common condition to focus on
here is called
Graves’ disease.
In this condition, the thyroid
gland is stimulated by antibodies that activate the receptor
for TSH on the follicular cell of the thyroid (
Figure 19–2
).
Therefore, these TSH receptor-stimulating antibodies mim-
ic the action of TSH, but are distinct from authentic TSH
from the anterior pituitary gland. These
thyroid-stimulating
immunoglobulins
(
TSIs
)
are characteristic of an autoimmune
disorder in which the patient makes antibodies that bind to
one or more proteins expressed in his or her own tissues (see
Table 18–11). TSIs are produced by B-lymphocytes that, in
addition to residing in lymph nodes, can actually infi ltrate the
thyroid gland in Graves’ disease. In Chapter 9, you learned
about a disease called myasthenia gravis, in which autoanti-
bodies bind to and destroy the nicotinic acetylcholine recep-
White blood cells,
antibodies,
and cytokines cause
eye symptoms
TSI release in blood +
within thyroid gland
Serum TSH
Anterior pituitary
TSH secretion
White blood cells in
lymph nodes + infiltrating
thyroid gland
TRH
(in hypothalamo-pituitary
portal vessels)
Target cells for thyroid hormones
Symptoms of thyrotoxicosis
Serum T
4
+ T
3
Thyroid follicle cell
Autoimmune
response
TSH
receptor
Begin
Hypothalamus
TRH secretion
White blood cells
infiltrate eye muscles
T
4
+ T
3
synthesis
I
uptake
Figure 19–2
Stimulation of thyroid hormone (T
4
and T
3
) release
by autoimmune production of thyroid-stimulating
immunoglobulins (TSIs) and resultant suppression of TSH
release via negative feedback inhibition. Notice that the eye
symptoms are caused by autoimmune response rather than by
the increase in thyroid hormones.
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