A thin thread of DNA is strong enough to connect diseases

[Guest guest]

All in the Family by Ross-Flanigan

Arthritis Today, NOVEMBER 2005

A thin thread of DNA is strong enough to connect autoimmune diseases

like lupus and rheumatoid arthritis to a common thyroid disease. Is

your family affected?

Some people live by the clock; for years, Diane Dupuis lived by her

alarm. " It took an enormous amount of effort just to get out of bed

in the morning, but at some point I'd have to. I had two little

ones – my daughter was turning eight, and my son was five – and I

had to get them to school or to swimming lessons in the summer. But

then I'd come home and nap and set the alarm for when it was time to

pick them up. When they got home, they'd play together, and I would

just lie on the couch. Then the alarm would ring, and either I'd go

make dinner or hope my husband was bringing dinner with him. "

It wasn't much of a life, and it wasn't the way she was used to

living. Before fatigue took her hostage, Dupuis was a dynamo,

putting in long hours as an executive at a Detroit-area publishing

company and still having energy to backpack, bicycle, kayak and ice

skate with her husband, play oboe in a summer concert band and

occasionally pitch at company softball games. What had changed her

into a lethargic homebody with no more get-up-and-go than one of her

couch cushions?

" Depression, " said the doctors she consulted. But the

antidepressants they prescribed didn't help. Dupuis suspected a

thyroid problem, but the doctors ran standard tests and interpreted

the results as perfectly fine.

Everything wasn't fine, though. Exhaustion shaded her whole

existence and eroded her self worth.

" I was very emotionally low and drained, " says Dupuis, 46. " I looked

with envy at what other women with children were accomplishing in

their lives and wondered what made me so incapable. " Finally, on a

friend's advice, Dupuis consulted another doctor who ordered more

informative tests and came up with a diagnosis that made sense:

Hashimoto's thyroiditis, an autoimmune disease, like rheumatoid

arthritis (RA) or lupus, that can shut down thyroid hormone

production, causing sluggishness and other symptoms.

Dupuis started on a treatment regimen that replaced the hormones she

lacked; almost immediately she began feeling better, she recalls. " I

felt so much better that after about four weeks, when I heard about

an appealing job opening, I had the energy and desire to pursue it. "

Taking that job when it was offered, however, involved a lot more

than just slipping into a suit and pumps and marching back into the

work force, which would have been impressive enough at that point.

It was in a different field – public relations instead of

publishing – and it required not a daily bus ride downtown, but a

move of more than 500 miles to northern Michigan. " My husband, kids

and I redid our whole lives and started over, " she says, and no one

was more amazed than Dupuis that she had the vigor for the

undertaking.

With her physical and mental health on the upswing, Dupuis still had

to wonder how she ended up with a hormone imbalance caused by an

autoimmune thyroid disease and what it meant for her continued

wellness. She started to remember relatives with suspiciously

similar health complaints – a grandfather who was turned down for

military service because of a goiter (a swollen neck caused by an

enlarged thyroid gland) and others with severe allergies and

arthritis, possible signs of immune systems gone haywire. Had her

family history set her up for thyroid problems? Could she also be at

risk for other autoimmune diseases like RA and lupus?

Connections Among Kin

A lot of patients wonder about patterns they see in their own

families. Like Dupuis, they're curious about connections between

hormonal problems, such as low thyroid hormone levels, and

autoimmune diseases, such as RA, and they want to know if those

conditions can be passed from one generation to the next. Medical

researchers are interested in the same kinds of questions, and

they're continuously learning about the interplay between hormones

and autoimmunity. It's a two-way street, they'll tell you.

Researchers have found autoimmune diseases can affect specific

hormones, as in thyroid disease, and various hormones – cortisol and

prolactin, for example – seem to be involved in a range of

autoimmune diseases, including RA and lupus. As for family

connections, Dupuis and other patients are right in thinking they

see patterns. Half the children, parents and siblings of people with

thyroid disease are susceptible to it, and there are strong genetic

links between thyroid disease and other autoimmune disorders,

including RA, type 1 diabetes and pernicious anemia. It's also not

unusual for more than one autoimmune condition to surface in the

same person.

" They tend to cluster in twos, " says Noel R. Rose, MD, PhD, director

of the Center for Autoimmune Disease Research at s Hopkins

University Schools of Medicine and Public Health, Baltimore. " When

you have one [autoimmune disease], then your chance of having

another is greater than in the general population. "

Researchers may be well aware of such connections, but the

information doesn't always trickle down to patients or their

doctors, found a 2002 survey by the American Association of Clinical

Endocrinologists (AACE). The survey showed more than three-fourths

of Americans were unaware that thyroid disease runs in families.

Almost 80 percent of respondents didn't realize there's a connection

between diabetes and thyroid disease, and 90 percent didn't know

that people with RA have an increased risk for thyroid trouble.

What does this mean if you or a relative has one of these

conditions? It's not a cause for alarm, says Dr. Rose, but it's a

reason to be aware of your family medical history and get informed

about conditions to which you may be susceptible. (See " Family

Affairs. " ) Learning a little about autoimmune thyroid disease is a

good place to start. It's the most common and best-studied organ-

specific autoimmune disorder, and its association with several other

autoimmune diseases is clear. If you or someone in your family has a

thyroid problem, chances are it has an autoimmune basis.

Balancing Act

You probably have at least a rough idea of where your butterfly-

shaped thyroid gland is – in your neck just above your collarbone.

But you may be surprised to learn just how essential a healthy

thyroid gland is to every organ, tissue and cell in your body. If

it's off kilter, you probably are, too.

Like all glands, the thyroid secretes hormones – chemical messengers

that travel through the bloodstream to carry out duties in other

parts of the body. The thyroid hormones triiodothyronine (T3) and

thyroxine (T4) influence all sorts of processes, from body

temperature regulation to metabolism and mental functioning. But the

thyroid gland doesn't just churn out hormones at a constant rate; it

operates as part of a finely tuned feedback loop that involves the

pituitary and the hypothalamus – glands in the brain that work

together to monitor and adjust levels of all hormones in the blood.

The way the system works is something like what happens when a

neighborhood volunteer group pitches in to make casseroles for

someone who's just had surgery. The group's president hears about

the operation and alerts the secretary; the secretary spreads the

word to the rest of the neighbors, who get busy in their kitchens. A

few days later, the secretary checks in with the recuperating

neighbor and finds out she's overrun with tuna casseroles and short

on freezer space, so word goes out to stop the flow of one-dish

dinners until her supply starts to dwindle. In the hypothalamus-

pituitary-thyroid loop, think of the hypothalamus as president, the

pituitary as secretary and the thyroid as a cluster of concerned

neighbors cooking up T3 and T4.

Problems with the thyroid gland itself or with the messages sent by

the hypothalamus or pituitary glands can make a mess of that

intricate regulatory system, resulting in too little or too much

thyroid hormone coursing through the bloodstream. With too little,

the whole body seems to be in slow motion: metabolism lags, leading

to weight gain; the brain works more slowly, affecting concentration

and memory; the gut gets sluggish, resulting in constipation.

Without treatment, low levels of thyroid hormones can lead to even

more serious problems, such as infertility, depression, high

cholesterol and subsequent heart disease.

Too much thyroid hormone isn't good either. Overproduction of

thyroid hormone, which can result from another autoimmune disorder –

Graves' disease – puts the body into overdrive, causing symptoms

like restlessness, speedy heart rate, insomnia and weight loss.

Causes That Concern

While autoimmune disease isn't the only cause of thyroid

malfunctions – radiation treatments, viral infections and certain

drugs can also affect the thyroid temporarily or permanently – it is

the most common. In the case of low thyroid function, there are two

main types of autoimmune disease, both classified as thyroiditis – a

condition in which the thyroid gland becomes inflamed and the immune

system turns against it – similar to what happens in the joints of

people affected by RA.

The more common type, Hashimoto's thyroiditis, sometimes runs in

families, says Dr. Rose. People with the disease may develop other

autoimmune disorders, particularly type 1 diabetes, which targets

the islet cells of the pancreas; 's disease, which targets

the cortex of the adrenal glands; pernicious anemia, which targets

the lining of the stomach; or RA and lupus, which target the immune

system itself, major organs and joints, he says.

No one knows for sure what sets the autoimmune process in motion,

why some genetically susceptible people get the disease and others

don't. One idea is that the trouble all starts with a viral or

bacterial infection, says R. Hamilton, Jr., MD, a professor

of medicine at the University of Texas Health Science Center in

Houston and president of AACE. The bug that causes the infection

contains proteins that are similar in some way to thyroid proteins,

the theory goes, and when the immune system goes on the attack, it

can't tell the difference, so healthy thyroid tissue is wiped out

along with the invaders.

For some women, though, the trigger is not a bug, but a baby. After

having her first baby 10 years ago, Kulick, 35, of

Winchester, Va., developed postpartum thyroiditis, the other main

type of autoimmune hypothyroidism, but it took six years until

doctors diagnosed it.

The condition appears in women two to six months after giving birth,

and sometimes is misdiagnosed as postpartum depression. Initially,

thyroid activity surges, resulting in temporarily high thyroid

hormone levels; after a few months, the thyroid gland becomes

underactive, and hormone levels drop too low. Levels usually even

out within a year, but after that initial recovery, about 25 percent

of women who've had postpartum thyroiditis develop permanent

hypothyroidism as much as four or more years later.

Kulick, who like Dupuis had always been active and fit, was

perplexed and frustrated when she could no longer muster enough

energy for a workout. Her emotions were at an all-time low, too.

" I wasn't my happy-go-lucky self; I wasn't interested in things I

normally would get very excited about, " she remembers. " I was very

detached from my friends and family. When stressed, I'd get that

lump-in-your-throat feeling you get if you're about to cry. "

To add to her stress, she had to consult several doctors before she

finally learned a diagnosis. " After several years of not feeling

right and trips to different doctors who said, `You're just tired

from being a new mom' or `You're depressed,' my true quest started

in an emergency room with a headache that woke me from my sleep, "

Kulick recalls. " They looked for a brain tumor or an aneurysm, so I

was told to follow up with a neurologist. He ran blood tests that

showed the autoimmune thyroid disease, and an endocrinologist

confirmed it. But along the way, I don't recall any doctor I saw

making the connection between my symptoms and my family history,

which includes a maternal grandmother with RA and a mother with

diabetes, " Kulick says.

Circling a Correct Diagnosis

The circuitous paths that Kulick and Dupuis had to navigate before

arriving at a diagnosis are typical, suggests a 2001 study by the

American Autoimmune Related Diseases Association. The organization

compiled survey responses from 500 women with one or more serious

autoimmune diseases and found that respondents visited an average of

four doctors in as many years before getting a correct diagnosis.

What's more, almost 45 percent of the women had been told at some

point during their quests that they were " chronic complainers "

or " too concerned about their health. " Those results were a little

better than in 1996, when a similar study revealed that women

typically visited six physicians over a five-year period before

getting an accurate diagnosis, and that 64 percent were labeled as

hypochondriacs.

Part of the problem is that many autoimmune diseases, including

autoimmune thyroiditis, affect more women than men and share some

symptoms with premenstrual syndrome, menopause and depression.

Frustrated, some women may half-heartedly accept those explanations

for their problems. Those who don't give up as easily often have to

press their doctors to check for other causes of their complaints.

It's not surprising then that autoimmune thyroid disease is grossly

underdiagnosed, especially in women. Though thyroid diseases of all

types affect more than 13 million Americans, more than half the

population has never been tested, according to AACE. But an analysis

of more than 17,000 people shows 17.4 percent of women older than 75

have hypothyroidism, as do 6.2 percent of men older than 65.

Ironically, hypothyroidism is one of the easiest conditions to

diagnose and treat. The first – and sometimes only – step is a

simple, inexpensive test called the sensitive thyroid-stimulating

hormone (TSH) test. Unlike older tests, which didn't detect problems

until the disease was fairly advanced, the TSH test detects thyroid

imbalances at early stages, sometimes before patients even notice

symptoms. About three years ago, AACE revised the guidelines for

interpreting TSH test results to help doctors identify which

patients need treatment. Previously, the range from 0.5 to 5.0 was

considered a normal TSH level. The range has shifted down; now 0.3

to 3.0 is considered normal. Patients whose TSH levels fall outside

that range should have their TSH levels monitored regularly, and

AACE encourages doctors to consider treating even mild thyroid

imbalances that would have been deemed normal in the past.

Doctors may also order other tests, such as the free T4 estimate

test and the thyroid-releasing hormone (TRH) stimulation test, which

some doctors feel can reveal underactive thyroid in patients whose

TSH tests are normal. The thyroid peroxidase test, which confirms a

patient's thyroid problem has an autoimmune basis by detecting

antibodies showing that the thyroid is under attack, also can

provide a diagnosis when the standard TSH, T3 and T4 tests and

physical exam are normal.

During a physical exam, your doctor may feel the front of your neck

to check the size of your thyroid gland. An enlarged thyroid gland

means it's growing tissue to try to meet production demands for the

important thyroid hormones. You can do a simple self-exam called the

Neck Check that helps you see if your thyroid gland is enlarged.

(See " Check Your Neck. " ) Enlargement of the thyroid gland is common,

but it's not always the rule. You'll want to see your doctor for

further testing if your thyroid gland is enlarged, advises the AACE,

but don't give up seeking a diagnosis if it's normal size but you

have a family history of autoimmune disorders and are experiencing

symptoms.

Living on Easy Treat

When it comes to correcting imbalances, hypothyroidism

is " completely treatable, simply by giving back the missing

hormones, " says Monach, MD, PhD, a postdoctoral fellow in the

immunology and immunogenetics research section at Joslin Diabetes

Center in Boston. As far as most doctors are concerned, that means

prescribing a synthetic version of T4 called levothyroxine

(Synthroid).

In the early stages of treatment, it's important to have your blood

tested as often as your doctor recommends, to make sure that your

dosage raises your thyroid hormone levels enough, but not too much.

You also need to let your doctor know if your symptoms don't improve

once you've reached the normal range – you may need slightly higher

or lower levels to feel normal. And be sure your physician knows

about other medications you're taking, because some drugs, including

corticosteroids, dopamine, calcium supplements, some antacids and

aspirin, can either interfere with levothyroxine absorption or

affect the results of thyroid function tests.