Unmasking Thyroid Disease
With symptoms that masquerade as myriad medical and mental disorders, thyroid disease
often eludes diagnosis.
By Alana Mikkelsen
Latasha Pettis had always been a good student, but during her sophomore year of high
school her grades plummeted and her personality changed dramatically.
The normally mild-mannered 15-year-old cursed at her French teacher and stormed out of
a classroom because of a minor misunderstanding. Routine reminders to do homework or
chores sent her into screaming and crying fits. In the winter, when her family nudged up
the thermostat in their East Palo Alto home, Pettis found the temperature so unbearable
that she rigged a makeshift sleeping place in the back yard.
"I thought Latasha was losing her mind," says her grandmother, Minnie Pettis.
A visit to a psychiatrist, however, would not have solved her problem.
Eventually, a swelling in Pettis' neck betrayed the cause of her bizarre behavior. Her
thyroid, a butterfly-shaped gland just below the Adam's apple, was five times larger than
normal and pumping out unusually high quantities of hormones.
Thyroid disease, which afflicts nearly 20 million people in the United States, often
masquerades as a variety of med-
ical problems. Consequently, underactive and overactive thyroid conditions may go
undiagnosed for months or even years, specialists say. The symptoms can be so subtle they
are missed. Or, like those of Pettis, they can be striking but confusingly similar to
other mental or physical disorders.
But when physicians recognize that another face may be lurking behind the mask, they
can help patients avoid extreme consequences of the disease -- ranging from digestive and
nervous system complications to heart failure and death. A simple blood test can detect
the disorder, and treatment is easy and effective, says I. Ross McDougall, MD, PhD, chief
of Stanford University Hospital's thyroid clinic.
"Thyroid disease is very common," says McDougall, professor of radiology and
medicine. "But suspected thyroid disease is even more common. Part of our job is to
show patients with suspected thyroid disease that they are normal rather than abnormal,
and if they are abnormal, prove that to the patients and determine the best
treatment."
"A high index of suspicion" toward any symptoms suggestive of thyroid disease
is very important, says McDougall, who runs the thyroid clinic within the division of
nuclear medicine. The clinic offers diagnostic testing and several forms of treatment for
overactive and underactive thyroid conditions and for thyroid cancer. McDougall works
closely with adult and pediatric endocrinologists, as well as surgeons, radiation
oncologists and ophthalmologists at the medical center.
Laura Bachrach, MD, a Stanford pediatric endocrinologist, referred Pettis to McDougall
for treatment of her condition: Graves' disease, the most common cause of an overactive
thyroid. Graves' disease, an autoimmune disorder, gained notoriety when physicians
diagnosed former President George Bush and Mrs. Barbara Bush with the disease.
The condition arises when antibodies produced by immune cells attach to receptors on
the surface of thyroid cells and mimic thyroid-stimulating hormone (TSH), the thyroid's
primary activator. Thyroid hormones, which influence metabolic processes and trigger cells
to consume energy and oxygen, aid the growth and development of nearly every tissue in the
body.
In the hyperthyroid condition, excess thyroid hormone produces a metabolic overdrive.
People with an overactive thyroid may appear nervous or anxious and have a racing heart,
warm and sweaty skin or diarrhea. They commonly feel hot in cool temperatures, lose weight
despite eating a lot and suffer from hair loss, muscle tremors and fatigue. Extreme
hyperthyroidism can put patients at risk of heart failure and incapacitation due to
dehydration.
A more common condition, an underactive thyroid gland or hypothyroidism, is
comparatively silent. Cases of hypothyroidism are considerably more common than those of
hyperthyroiditis, says Bachrach.
As in the overactive condition, the most common cause of an underactive thyroid is an
autoimmune disorder-- called Hashimoto's disease. Also called chronic lymphocytic
thyroiditis, Hashimoto's disease results when antibodies latch on to proteins in the
thyroid tissue. The binding is a call to action to the rest of the immune system, and the
thyroid is subsequently invaded by numerous immune cells, or lymphocytes, which
progressively destroy the hormone-producing thyroid tissue in an errant attempt to rid the
body of what it thinks is an invader.
The resulting hormone deficiency slows metabolism and causes people to lose their
appetite, become lethargic, gain weight and suffer from constipation. Dry skin and hair,
brittle nails, a puffy face and muscle cramps are common. Prolonged hypothyroidism can
make adults forgetful and can lead to hypertension and organ damage.
Children, who may be oblivious to some of the disease's subtle symptoms, are more
likely to progress to longstanding hypothyroidism than adults.
"Children don't focus on their weight as much [as adults]. They may not notice
subtle changes in energy. Their mood may be attributed to a stage they're going through,
and they don't get as frantic if they get constipated as older people do," says
Bachrach. "I've seen children who have profound hypothyroidism that's gone on for six
or seven years who've never complained."
Growth in hypothyroid children typically stops "right in its tracks," says
Bachrach. For instance, a hypothyroid child whose height is in the 50th percentile for his
age one year may measure as tall or taller than only 20 percent of his peers the next
year. Taken at face value, the child's height for both years would be plotted within
average ranges of stature. But Bachrach warns against the misconception that as long as
children's absolute heights are normal, their underlying health is fine.
"That kind of change in growth percentiles is very abnormal," she notes.
From the age of two until puberty, a child should remain at roughly the same place on a
growth curve, Bachrach says. Any significant change in growth rate -- the crucial
indicator of normal development -- should be taken seriously. Bachrach notes that
physicians should make sure their young patients' heights are plotted on growth curves and
compared with measurements from previous years. And parents should be suspicious if their
child rarely changes shoe or clothing size.
Spotting hypothyroidism in adults can require an even more critical eye. Like all
autoimmune disorders (including Graves'), hypothyroidism preferentially attacks females.
And, because it most commonly occurs after mid-life, it is often mistaken for menopause.
In addition, about one in 20 women will be afflicted by a short-term change in thyroid
function immediately following pregnancy. The disorder -- in which the thyroid usually
becomes overactive then underactive with consequent changes in mood -- can easily be
mistaken for postpartum depression. Women with insulin-independent diabetes have a higher
risk for this transient disorder, which usually returns to normal after several months.
In both Graves' and Hashimoto's diseases, lymphocyte infiltration -- in which immune
cells home to and penetrate a site of immune attack -- can lead to a goiter, or swelling,
of the thyroid gland. Few goiters are as large as Pettis' plum-sized swelling, but they
are often a cause of concern.
"A lot of parents notice the swelling, and they get anxious because they think it
is a tumor," says Bachrach. Thyroid cancer is rare, however, and most enlarged
thyroids are benign, she notes.
In 90 percent of Hashimoto's cases, for example, the thyroid gland is not damaged
enough to produce a hormonal imbalance. This condition, called euthyroidism, does not
require treatment. Some of these goiters disappear without therapy, but physicians should
monitor patients with Hashimoto's thyroiditis because they are at greater risk of
developing hypothyroidism later in life, McDougall says.
When a goiter or other symptoms lead physicians to suspect a thyroid condition, they
typically use blood tests to measure thyroxine and TSH levels in the blood. Thyroxine
comes in two forms: free and bound to protein. Only the free form of the hormone is
metabolically active, and McDougall cautions that total thyroxine measures can give an
inaccurate result and may lead physicians to prescribe unnecessary treatment.
McDougall also warns physicians to be alert to coincidental conditions that can throw
the tests off -- for example, acute psychiatric conditions and some medications for heart
arrhythmias, as well as narcotics like cocaine. In the early 1980s, McDougall and the late
Joseph P. Kriss, MD, (McDougall's predecessor in the thyroid clinic), found in patients
they studied that up to half of patients with psychiatric and severe physical illnesses
had abnormal thyroid tests. When these illnesses subsided, the tests returned to normal.
After making the thyroid disease diagnosis, physicians can usually cure the patient.
The simplest form of thyroid disease to treat is hypothyroidism. Synthetic hormone
replaces the natural insufficiency, and patients usually take substitute pills daily at a
cost of between $60 and $80 a year.
An overactive thyroid gland is more challenging to treat. Drug therapy, which consists
of pills that must be taken up to three times a day, is inconvenient and may have
undesirable side effects such as a rash. For that reason, many patients -- including
Pettis -- opt for radioactive iodine therapy, which destroys the overactive gland.
Surgical removal of the thyroid is an alternative means to permanently "cure"
hyperthyroidism.
"Most patients who hear about treatment with radioactive iodine get a little
anxious," McDougall says, "but it's the safest, simplest, cheapest and best
approach to treating hyperthyroidism."
Patients take the treatment in the form of a tasteless, odorless drink, and one
treatment is usually all it takes. The thyroid gland needs iodine to make its hormones and
is one of the few places in the body where iodine is metabolized, so most of the
radioactive iodine homes to the gland. Because patients are mildly radioactive for a few
days following treatment, they are usually required to sleep alone, wash their personal
clothes and bed sheets separately from family members and use disposable plates and eating
utensils.
McDougall says the risk of damage to others from exposure to radioactivity is extremely
small. "If you sat three feet from a patient for one hour, you would be exposed to
about the amount of radiation that you would get from two days of background [from the sun
and earth]," McDougall says. "If you slept beside someone for eight hours, you
would get about eight times that. That's still a very small amount of radiation."
After a few days, the radiation given off from the patient is virtually imperceptible,
he adds.
Because radioactive iodine eventually destroys the thyroid gland, most patients who
take the treatment become hypothyroid after several months. Like those with naturally
underactive thyroid glands, they require hormone replacement for the rest of their lives.
McDougall says most patients find trading hyperthyroidism for hypothyroidism definitely
worthwhile.
"It's quite dramatic," he says. "In about six weeks, patients can be
made normal. About three months later they go on a replacement pill and can pretty much
get away from doctors once the dose of thyroxine is adjusted, although a blood test every
year or two is recommended."
Indeed, Pettis has bounced back after her radioactive iodine treatment. Her grade point
average has jumped from last year's 1.8 up to 3.0, and in June she was inducted into the
National Honor Society. This summer she'll become hypothyroid and begin taking replacement
hormone.
She says the lifelong treatment is a small trade-off for the possible dire consequences
of staying hyperthyroid.
"I feel great," Pettis says. "I feel better, I act better and my
attitude is positive."
Pettis' turnaround is satisfying to McDougall, as well.
"There are very few areas in medicine where you can actually cure patients,"
he says. "... but with thyroid disease you frequently can."
Graves' consequences
Itchy, watery, sandy-feeling eyes. Swollen eyelids. Allergy medication won't cure these
irritating symptoms if the underlying problem is a mysterious eye disease called Graves'
ophthalmopathy, which can spontaneously appear or insidiously progress toward Eyelid
swelling, double vision and varying degrees of sight loss.
Although it usually accompanies Graves' disease (see main story), Graves'
ophthalmopathy may appear immediately before or decades after a patient has been treated
for hyperthyroidism. The eye condition may also be associated with an underactive thyroid
or no thyroid condition at all.
Some researchers suspect the disease is caused when antibodies already present against
the thyroid gland migrate toward the eye and attack the connective tissue and muscles of
the orbit -- the bony socket in the skull that houses the eyeball and eye muscles.
Inflamed by the immune attack, the muscles can become stiff. Often the eye muscles swell
so much that they push the eyeballs out toward the front of the face. The resulting
bulginess can dry out and damage the cornea -- the eye's protective surface -- and can
severely affect a person's appearance as well as self-image. Sometimes patients have
difficulty closing the eyelids, which causes a characteristic stare.
"The eye socket is surrounded by bone, so there's no place for the swollen tissues
to go but forward," explains Peter Levin, MD, chief of ophthalmic and orbital surgery
in Stanford's department of ophthalmology.
In severe cases, the swollen muscles press on the optic nerve and endanger a person's
sight. Such serious cases are uncommon and can be treated with an operation called
surgical decompression. During the procedure, the surgeon removes one or more of the bones
that separate the orbital cavity from the sinuses. The swollen membranes can then expand
inward and the eyes sink back to their proper place in the face.
Other symptoms of Graves' ophthalmopathy, including double vision or cross-eye, can be
surgically corrected by cutting the muscles on either side of the eye and reconnecting
them at a position that pulls the eyeballs back to center. The operation is difficult,
Levin says, because the muscles must be precisely aligned and the patients are asleep at
surgery. However, an "adjustable suture" used by Stanford eye surgeon Deborah
Alcorn, MD, gives doctors a second chance. The stitch -- effectively a slipknot -- allows
the doctor to reposition the muscle's connection to the eye in the office on the day
following surgery, Levin says.
At Stanford, physicians most commonly treat progressive Graves' ophthalmopathy by
aiming a fine X-ray beam at the eye muscles. The technique, which was developed at
Stanford for treating cancer, uses a medical linear accelerator -- a compact version of
the huge "atom-smashers" physicists use to study atomic particles. The medical
version of the machine uses pulses of microwave energy to excite electrons to near-light
speed, then aims them against a gold-plated target. The resulting collision produces
highly penetrative X-rays, which are emitted from the machine and targeted to the
patient's orbital muscles.
The lymphocytes that create the inflammation are particularly sensitive to radiation
and are preferentially killed by the low dose of X-rays. Once the culprit cells have been
killed, the swelling in the connective tissues usually regresses.
"There are several good places in the country that can do the same [eye]
treatment, but we remain ... the one with the longest history and the largest number of
treated patients," says Sarah Donaldson, MD, Stanford professor of radiation oncology
and past president of the American Society for Therapeutic Radiology and Oncology.
Donaldson conducted the first study to follow the effectiveness of radiation treatment
for Graves' ophthalmopathy, which began in the late 1950s under the direction of Malcolm
Bagshaw, MD, former director of Stanford's radiation oncology department, and the late
Joseph P. Kriss, MD, professor of nuclear medicine and a specialist in thyroid disease.
The interdepartmental cooperation continues today. Donaldson, Levin and thyroid
specialist I. Ross McDougall, MD, PhD, collaborate on the diagnosis and treatment of each
Graves' disease patient who comes under their care. The teamwork has contributed to the
success of more than 400 patients who have undergone radiation therapy for Graves'
ophthalmopathy at Stanford, Donaldson says.
"Our opinion has always been that we should treat ophthalmopathy if it's
progressive -- not if it's stable, but if it continues to get worse and there are signs
and symptoms that ... a functional impairment may affect the patients' ability to perform
a job, take care of themselves or live independently," Donaldson says.
"By using the treatment selectively," she says, "80 to 90 percent of our
patients have their worrisome, troublesome problems go away."
-- Alana Mikkelsen
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