common cause of hyperthyroidism, Graves’s dis-
ease affects seven times as many women as men
and is most frequent among women between the
ages of 30 and 60. Graves’s disease is more likely
to occur among people who have other AUTOIM-
MUNE DISORDERS, notably type 1 DIABETES, SYSTEMIC
LUPUS ERYTHEMATOSUS(SLE), and POLYGLANDULAR DEFI-
CIENCY SYNDROME.
In health the HYPOTHALAMUS, PITUITARY GLAND,
and thyroid gland work in synchronization to
maintain an appropriate balance of thyroid hor-
mones, which regulate METABOLISM, in the BLOOD
circulation. Low blood levels of the major thyroid
hormones TRIIODOTHYRONINE(T 3 ) andTHYROXINE(T 4 )
signal the hypothalamus to produce THYROTROPIN-
RELEASING HORMONE(TRH). TRH in turn stimulates
the pituitary gland to secrete THYROID-STIMULATING
HORMONE(TSH). TSH binds with TSH receptors on
the cells of the thyroid gland, activating synthesis
of T 3 and T 4. When T 3 and T 4 reach appropriate
levels in the bloodstream, the hypothalamus stops
producing TRH and the thyroid hormone cascade
ends.
The antibodies the IMMUNE SYSTEM produces
in Graves’s disease, called thyroid-stimulating
immunoglobulins (TSIs), continuously stimulate
the TSH receptors in the thyroid gland, falsely sig-
naling that blood T 3 and T 4 levels are too low. The
thyroid gland responds by increasing synthesis of
these hormones. It is an overproduction, however.
TSH and TRH levels fall as they should but thyroid
hormone production continues in the thyroid
gland, resulting in hyperthyroidism. Graves’s dis-
ease accounts for about 70 percent of hyperthy-
roidism in the United States.
A serious corollary condition is GRAVES’S OPH-
THALMOPATHY, in which the excessive thyroid hor-
mones cause swelling in and around the
structures of the eyes. Graves’s ophthalmopathy is
often the earliest indication of Graves’s disease
and can result in permanent damage to the eyes,
including loss of vision. The characteristic symp-
tom of Graves’s ophthalmopathy is EXOPHTHALMOS
(bulging eyes, also called poptosis). Some endocri-
nologists believe Graves’s ophthalmopathy is a dis-
tinct autoimmune disease process separate from
Graves’s disease, as it may exist without apparent
hyperthyroidism or develop years to decades
before or after hyperthyroidism manifests.
Symptoms and Diagnostic Path
The symptoms of Graves’s disease are those of
hyperthyroidism and may include symptoms of
Graves’s ophthalmopathy as well. These symp-
toms are- PALPITATIONS
- weight loss
- heat intolerance
- difficulty concentrating
- irritability, anxiety, and insomnia (difficulty
sleeping) - bulging eyes (poptosis), “lid lag” (delay in the
eyelid’s movement when the EYEmoves down-
ward), and vision disturbances (Graves’s oph-
thalmopathy)
The diagnostic path includes blood tests to
measure thyroid hormones (typically T 3 , T 4 , and
TSH) and the presence of TSIs. The former estab-
lish hyperthyroidism; the latter confirms the diag-
nosis of Graves’s disease.Treatment Options and Outlook
Treatment targets disabling the thyroid gland’s
ability to synthesize thyroid hormones. Because
Graves’s disease is a progressive autoimmune dis-
order, endocrinologists tend to opt for permanent
therapies such as radioactive iodine (^131 I) to
destroy thyroid tissue so it cannot produce thyroid
hormones. One consequence of this approach is
that the destruction of the thyroid gland results in
permanent hypothyroidism and makes necessary
lifelong HORMONE THERAPYwith thyroid hormone
supplements. Thyrotoxic medications such as
methimazole and propylthiouracil (PTU), though
effective in other forms of hyperthyroidism, are
less successful because the autoimmune response
continues.Risk Factors and Preventive Measures
Women who have other autoimmune disorders
have increased risk for Graves’s disease. For them,
regular blood tests to measure thyroid hormones
can help detect the condition early. Routine oph-
thalmologic examinations can detect Graves’s
ophthalmopathy, which may develop even with
treatment for Graves’s disease, before it causes130 The Endocrine System