The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (16 page)

A complete blood count (CBC) and metabolic profile are needed to rule out anemia, abnormal liver function, excess calcium in the blood (
hypercalcemia
), and other possible causes of symptoms.

Thyroid stimulating hormone (TSH)
levels are the best indicator of thyroid function. TSH is increased in women with hypothyroidism and is low or undetectable in women with hyperthyroidism, says Dr. Rose. The most sensitive test, capable of detecting very low levels of TSH, is called a third generation assay. The normal range for TSH is 0.4 to 5.5 micro international units per milliliter of blood (
µ
IU/ml), but ideally a young, healthy person should have a TSH below 3.0. A woman with hyperthyroidism usually has a TSH below 0.1
µ
IU/ml; in hypothyroidism, TSH is elevated above 5
µ
IU/ml.

Total and free thyroxine (T4)
are measured separately. A test for total T4 measures all of the circulating thyroxine; a test for free T4 measures only the biologically active thyroxine (the amount that is not bound up by serum-binding proteins and can attach to hormone receptors in cells). The normal reference range for free T4 in nonpregnant women is 0.8 to 2.7 nanograms per deciliter of blood (ng/dl). The normal range for total serum T4 is 4.5 to 12.5 micrograms per deciliter of blood (mcg/dl). A woman with Graves’ disease would have a total T4 above 12 mcg/dl; a hypothyroid woman would have a T4 below 5 mcg/dl.

Total triiodothyronine (T3)
measures the amount of circulating T3, which can be influenced by factors that change levels of thyroxine-binding globulin, including estrogen. Normal levels of T3 range from 0.4 to 4.2
µ
IU/ml. This blood test may only be done if additional information is needed about thyroid function.

Thyroid antibody blood tests
look for autoantibodies to components of the thyroid cells (thyroid antibodies), such as antibodies to
thyroglobulin (TG)
and
thyroperoxidase (TPO)
. “More than 80 percent of women with Hashimoto’s disease also have antibodies to thyroid peroxidase,” says Dr. Rose. “Since they are not overlapping almost all Hashimoto patients have antibodies to one or the other, or both thyroid specific antigens.”

Antibodies against the TSH receptor (TRAbs)
are found in the blood of almost everyone with untreated Graves’. Serum TRAbs, along with elevated TSH and signs of Graves’ ophthalmopathy, can confirm a diagnosis.
²

Radioactive iodine uptake (RAIU)
may normally be ordered if a woman has thyroid nodules or a goiter (and may be done in conjunction with a thyroid scan). The iodine that we take in from food is absorbed by the thyroid gland and is a key building block of thyroid hormones. The test involves
giving a small amount of oral radioactive iodine and measuring the amount absorbed by the thyroid gland; the normal range of absorption is 8 to 30 percent after 24 hours.
²
Radioactive iodine will be elevated above 30 percent in women with Graves’ disease. It will also be elevated in postpartum thyroiditis, and in women taking replacement thyroid hormone.

A thyroid scan
uses a special detector that’s able to see how much radioactive iodine has been taken up by the thyroid and how evenly it’s dispersed in thyroid cells. If the radioactive iodine is taken up by the entire thyroid, it rules out the possibility that overactive nodules are causing hyperthyroidism. A benign nodule producing too much thyroid hormone will be “hot” on the scan, in contrast to a “cold,” hypofunctioning nodule, which can be benign or malignant.
²

Ultrasound examination of the thyroid
may be done if your doctor feels nodules when examining your thyroid. Ultrasound uses sound waves to create pictures of thyroid nodules felt on examination to determine whether they are solid or fluid-filled (it can also show nodules that can’t be felt).

Needle aspiration biopsy may be performed if a nodule looks suspicious. In this procedure, a small needle is inserted into the nodule to withdraw a small amount of fluid or cells for analysis. This test is 90 percent accurate in detecting cancer. Most of the time, these nodules turn out to be benign. A recent study found that, during five years of follow-up, cancer was found in only 0.3 percent of thyroid nodules.
⁷

Anne Marie’s story continues:

After I was diagnosed with Graves’ disease, they gave me drugs to slow down my thyroid. I would go through periods of feeling very tired and periods of feeling very awake, hyper-awake. Then they ablated my thyroid with radioactive iodine. You go into a hospital, down to nuclear medicine, and they give you this tablet. It looks like an ordinary pill, but it’s radioactive. And it made me feel very strange. It makes you feel like you’re sweating out of your pores, you feel lethargic, kind of out of it. At least that’s how I felt. I had some thyroid tissue left over after the ablation, and it was very hard to regulate my thyroid. I needed blood tests every few weeks. But I take my thyroid pill religiously every day. Sometimes my numbers are out of whack and they have to give me less, and sometimes they have to up the dose. It’s been a long process.

Hypothyroidism is treated with synthetic
levothyroxine sodium (synthetic T4)
to normalize levels of thyroid hormone. The goal of treatment is not only euthyroid blood levels of thyroid hormones but also the resolution of signs and symptoms. You want to feel “well.” According to 2014 treatment guidelines from the American Thyroid Association (ATA), “steady-state” levels of thyroid hormones in your body are generally reached about six weeks after you start therapy. The goal is to be within the “reference ranges” (average blood levels) of TSH.
⁸

It may take some time to find the right dose for you. If the dose isn’t high enough, hypothyroid symptoms may persist and your cholesterol may rise. If the dose is too high, you may develop symptoms of an overactive thyroid, as well as heart rhythm problems or even bone loss. This may be more pronounced in older women.
⁸
So, generally doses are gradually increased until blood levels of TSH are in the normal, euthyroid, range and your symptoms resolve.

One may not always accompany the other, the ATA acknowledges; some women may not notice differences between dose levels while others may not feel “well” on a dose that produces thyroid hormone levels within the normal range. Since symptoms like cold sensitivity and sluggishness and signs such as dry skin can’t be measured as hormone levels can, blood tests play a key role in determining your dose.
⁸
There are also physiological signs such as heart rate, as well as symptoms like depression or anxiety levels, that can be monitored. But you’ll have to work closely with your endocrinologist to achieve the best quality of life. Annual physical exams and blood tests are needed to make sure thyroid hormone levels stay in the normal range and symptoms haven’t returned.

Hashimoto’s goiters may shrink by almost a third over a two-year period with T4 supplementation. Around 10 percent of women may have a spontaneous remission four to eight years after starting treatment. But in some cases thyroid failure is progressive, and levothyroxine doses may need to be increased as the thyroid continues to slow down.

Levothyroxine is sold by prescription under a number of brand names, including
Synthroid
,
Levothroid
, and
Levoxyl
. According to the ATA, if you start on a brand name and are doing well, you should stick to that brand. As for generics, given changing drug formularies within the same insurance company, there’s no way to assure that you’ll get the same formulation each time. “Bioequivalence is not therapeutic equivalence” and “switching of products could lead to perturbations in serum TSH,” the ATA guidelines state. If a change in product is made, thyroid function tests should be rechecked, the treatment guidelines advise.
⁸

The ATA also recommends that levothyroxine be taken an hour before breakfast or at bedtime (three hours after any evening snack) to ensure the best absorption. Fiber and soy may impair absorption, as can that morning cup of coffee (another reason to take it at bedtime).
⁸

The absorption of levothyroxine be impaired by other drugs, including male hormones (
androgens
); antacids containing
aluminum hydroxide
(such as
Rolaids
); acid reducers called proton pump inhibitors (PPIs) such as Nexium; antidepressants like
fluoxetine (Prozac)
,
amitriptyline (Elavil)
, and
phenelzine sulfate (Nardil)
; blood thinners such as
warfarin (Coumadin)
; insulin; digitalis-type drugs such as
digoxin (Lanoxin)
; iron supplements;
cholestyramine (Colestid, Questran)
; calcium supplements; and multivitamins containing calcium and iron. So take your thyroid hormones separately, the ATA advises.
⁸

Postmenopausal women taking hormone therapy (HT) may need higher doses of thyroid hormone (see
page 122
).

You’ll need periodic bone scans after menopause to check for bone loss, and because mild thyroid hormone excess over many years may increase the risk for heart rhythm problems, you may also need periodic electrocardiograms.

Both the ATA and the American Association of Clinical Endocrinologists (AACE) recommend against taking dietary supplements that claim to enhance thyroid function.
⁹

In Graves’ disease, the overactive thyroid gland must be calmed down or destroyed, and then replacement thyroid hormone is given.

Antithyroid drugs
, including
propylthiouracil (PTU)
and
methimazole (Tapazole)
, make it harder for the thyroid to use iodine to make thyroid
hormone, which lowers secretion of thyroxine. PTU and methimazole are typically used in mild Graves’ disease (or when Graves’ occurs in children or young adults) and are often prescribed for elderly women who also have heart disease.
¹⁰
Women over age 65 who have chest pain or irregular heart rhythms may suffer heart damage if they become more hyperthyroid. PTU is given three times a day, methimazole is given once a day.
¹⁰

Treatment with radioiodine (
page 113
) may temporarily boost levels of thyroid hormone; giving antithyroid drugs prevents this increase.
¹⁰
Between 20 and 30 percent of women with early, mild Graves’ disease will experience a prolonged remission after 12 to 18 months of treatment with antithyroid drugs. As many as 40 percent of patients may have a permanent remission.

However, PTU and similar drugs sometimes provoke allergic reactions. About 5 percent of women may develop skin rashes, hives, or, less commonly, fever and joint pain. In some cases, these drugs may cause a decrease in certain white blood cells (neutrophils), which may increase the risk of infections. In rare instances, white cells may actually disappear entirely, causing
agranulocytosis
, which can be fatal if you get a serious infection. If you’re taking an antithyroid drug and develop an infection (such as strep throat), call your doctor immediately and ask if you need to get a white blood cell count. If white blood cells have been decreased, stopping the drug can return the neutrophil count to normal. During therapy you should also avoid immunizations with live virus vaccines,
¹¹
as methimazole can lower the body’s resistance and may lead to the very infections vaccines are designed to prevent.

These drugs may also cause liver problems. Signs of trouble can include jaundice (skin and white of eyes turn yellow and urine turns darker), joint pain, fever, nausea, and abdominal pain. PTU and MMI can also cause an itchy rash or sore throat (pharyngitis).
¹⁰

If you go into remission, antithyroid drugs will be continued for another year or two. Signs of a remission include a decrease in the size of the thyroid and a near-normal or higher TSH. But neither is a reliable predictor, and more than half of patients will develop a recurrence within five years. You’ll need to be monitored by your doctor every three months for the first year of treatment and annually after that.

Radioiodine/radioactive iodine (or iodide)
accumulates in the thyroid and damages thyroid cells, reducing the amount of hormone-producing tissue. Radioactive iodine emits two types of radiation:
gamma rays
, which travel
through tissue and can be seen with a special detector (as in thyroid scans); and
beta rays,
which travel only a few millimeters and are absorbed by thyroid cells. The beta rays don’t kill the thyroid cells but cause enough inflammation and DNA damage to prevent them from producing too much thyroxine and from reproducing. The dose is determined by how much radioactive iodine is absorbed by the thyroid during an uptake test.

Radioactive iodine is given in capsule form (taken with lots of water). Within 24 to 48 hours, most of the radioactive iodine will be taken up by the thyroid, and the remainder is excreted in urine (or decays into a nonradioactive state). The level of radioactivity of the iodide left in the thyroid declines by 50 percent every five to seven days. It’s not going to be harmful to family members, but it might be wise to limit contact with infants and pregnant women for the first week after taking the radioisotopes, just to be safe.

Because of increased inflammation (and possibly increased autoantibodies) in the thyroid caused by radioactive iodine, secretion of thyroxine will be greater for a few weeks, and may heighten symptoms, especially in older women and those with heart disease (for that reason, antithyroid drugs are given beforehand). You’ll likely begin to improve in three to six months, but there’s a chance you may remain hyperthyroid and need a second or third dose.
¹⁰
A majority of women become hypothyroid after treatment and need replacement thyroid hormone.

The word
radioactive
may sound scary, but no serious complications from treatment have been seen in 50 years of using the drug. In fact, more than 70 percent of American adults with hyperthyroidism are treated with radioactive iodine, with no increased risk of cancer.

If you plan to become pregnant, you must wait three to six months after treatment before trying to conceive.
¹⁰
This is to ensure your baby will not be exposed to radioactive iodine, which can cause developmental problems and destroy the baby’s thyroid.

Thyroidectomy
, surgical removal of the thyroid, may be advised if you’re allergic to antithyroid drugs, don’t wish to take radioactive iodine, have a large goiter, or are pregnant.
¹⁰
First, hyperthyroid symptoms need to be brought under control with an antithyroid drug or a beta-blocker (which controls the effects of too much thyroid hormone), so that there is not an abrupt increase in hormones. The drugs are usually given a week or two prior to surgery. Surgery cures hyperthyroidism, but you still can become hypothyroid
afterward and will need yearly blood tests to measure thyroid function and levothyroxine.

Beta-blockers may be needed if you’re undergoing any of these treatments to reduce symptoms until the therapy takes full effect. These drugs—including
propranolol (Inderal)
,
atenolol (Tenormin)
, or
metoprolol (Lopressor)
block the effects of circulating thyroid hormone in the body, helping to slow heart rate and lessen anxiety and nervousness. Patients who can’t take beta-blockers include women with asthma and heart failure (which may be worsened by beta-blockers) and people with diabetes who take insulin (because symptoms of low blood sugar may be masked while on these drugs).

Most of the time, Graves’ ophthalmopathy is a mild problem that does not damage the cornea or impair vision. However, if your lids do not completely close, your eyes can dry out at night. Special adhesive tapes normally used for first aid can be used to tape the lids closed while you sleep, or you can wear an eye patch. Artificial tears can also be used during the day for added lubrication (see
pages 184
to
185
), side panels for glasses lessen air flow around the eyes to prevent dry eye, and tinted glasses can ease light sensitivity.

Surgery
to remove swollen tissue and decrease the opening of the eyes can lessen the appearance of a prominent stare. You’ll need to consult an ophthalmologist to determine the type of surgery and its timing.

Corticosteroids
are used to reduce inflammation and lessen swelling of tissue around the eye in cases of severe congestive ophthalmopathy. Oral steroids such as
prednisone (Deltasone)
and
methylprednisolone (Medrol)
can be used for short periods of time, or in low doses for longer periods to relieve redness, swelling, and eye pain. Side effects include weight gain, muscle weakness, and, with long-term treatment, an increased risk of osteoporosis, bone fractures, diabetes, high blood pressure, and infection (discussed on
pages 42
to
43
).

Radiation therapy
, which directs low doses of radiation to the area around the eyeball, has been widely used for decades, but the actual benefits of the procedure are still uncertain.
¹²
In recent years it has been used less frequently and may be done only when corticosteroids are no longer effective.

Corrective eye surgery
removes or repairs swollen muscles around the eye that can cause pressure on the optic nerve and double vision. The surgery should be performed by an ophthalmic surgeon only after ophthalmopathy has been stable for three to six months.

Orbital decompression surgery
, which enlarges the bony opening around the eyes to provide more space for the eye and eye muscles, is done only when other treatments fail.

Risk factors for Graves’ ophthalmopathy include smoking, radioiodine therapy for hyperthyroidism, and hypothyroidism following radioiodine treatment.
¹⁰