Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (17 page)
While the ratio of males to females is about equal in juvenile thyroiditis, after puberty it’s more common in females, suggesting that female hormones play a role in thyroid disease.
Estrogen and progesterone both exacerbate thyroid inflammation, and thyroiditis can be reversed with testosterone, as shown in experiments with mice bred to have an animal model called
experimental autoimmune thyroiditis (EAT).
“When the testes were removed in the mice and we gave them estrogen, they became more susceptible to thyroiditis. When we removed the ovaries of the female mice and gave them testosterone, they became less susceptible to thyroiditis,” says Dr. Rose.
During pregnancy autoimmune thyroiditis gets better, but in the year after giving birth it worsens. Some studies show that in women with mild thyroid inflammation, the increased immune response after pregnancy (remember, the immune system has modulated its responses to tolerate and protect the growing fetus)
13
tips the balance and may cause thyroid dysfunction (
postpartum thyroiditis
). And up to 25 percent of women may develop a permanent autoimmune hypothyroidism within 10 years after delivery. There’s also an increased risk of developing Graves’ disease in the postpartum period. However, estrogen is not the whole story. There are other hormonal influences, such as stress hormones, that may come into play.
Fetal cells that enter the maternal circulation during pregnancy may contribute to autoimmune thyroid disease, says Terry F. Davies, MD, the Florence and Theodore Baumritter Professor of Medicine at the Mount Sinai School of Medicine in New York and Director of their Division of Endocrinology and Metabolism at the James J. Peters VA Medical Center. In one study of mice, Dr. Davies’s research team found fetal cells in the thyroid glands of mice with EAT during pregnancy and the postpartum period but none in mice without EAT. Dr. Davies and other researchers have also isolated cells containing the male chromosome in thyroid tissue from women undergoing thyroid surgery who had previously given birth to boys.
“The theory is that during pregnancy the fetal cells actually suppress thyroid disease, in the same way that the immune system is suppressed and doesn’t attack the fetus. And that may be why the thyroid disease improves during pregnancy,” explains Dr. Davies. “Once the placenta and the baby are gone, then the number of fetal cells starts to fall rapidly and their ability to suppress the thyroid disease decreases, and you get a recurrence.”
The fetal cells may be attracted to the thyroid by inflammation. “The inflammation would be organ specific. If you start off with thyroid inflammation, thyroiditis, fetal cells may accumulate in the thyroid. If you start out with beta cell destruction in diabetes, then fetal cells may be attracted to the pancreas,” he adds.
However, the exact relationship between fetal cells and autoimmune thyroid disease is still unknown, as is the relationship between environmental factors such as stress or infections and female hormones.
It wasn’t until years after I was diagnosed with Hashimoto’s that I found out I had a strong family history of thyroid disease. My father had a goiter, one of his first cousins had Graves’ disease, and another has Hashimoto’s. Their children also had thyroid disease; one of them also has lupus. But until I asked questions, no one had ever mentioned it. It wasn’t regarded as important, not like if someone had cancer. I got my period late, around age 14, and maybe that was the beginning of it. My mother took me to a gynecologist, who couldn’t find anything wrong. Back then, and we’re talking maybe 50 years ago, no one even thought to look. Now I know Hashimoto’s can occur when you are a teenager.
L
YNNE
, 67
Menstruation and Fertility
Women with Hashimoto’s thyroiditis often have heavier periods that last for longer than a week. They may also have bleeding between periods because of a failure to ovulate (
anovulation
). Normally, the ovaries are stimulated to produce an egg in the first part of the menstrual cycle, the follicular phase. After ovulation, in the luteal phase, the uterine lining builds up an extra layer of blood vessels in preparation for a fertilized egg. If pregnancy doesn’t occur, the lining is shed as menstrual flow. In Hashimoto’s, the normal hormonal feedback between the ovaries, the pituitary, and the hypothalamus is disrupted. So a woman may fail to ovulate, but the uterine lining will continue to be stimulated, so bleeding can occur outside the normal cycle. Anovulation is common in hypothyroidism.
Hashimoto’s is also associated with primary ovarian insufficiency (POI), (formerly called premature ovarian failure, see
pages 231
to
233
). In women with Graves’ disease, an increase in metabolism causes a decrease in menstrual flow and a shorter cycle. A woman whose period normally lasted four or five days may see it decrease to two or three days. In severe hyperthyroidism, some women stop having periods altogether.
Taking oral contraceptives containing estrogen can also increase the amount of
serum thyroxine binding globulin
, which makes T4 less available to cells. Women with normal thyroid function will secrete more thyroxine to compensate, but women with Hashimoto’s can’t produce the extra T4, remarks Dr. Rose. This also occurs during pregnancy, mainly due to increased estrogen levels, and in women taking estrogen therapy (ET) after menopause (see
page 122
).
Pregnancy has a number of effects on the thyroid gland due to hormones (especially the pregnancy hormone hCG) and the body’s increased metabolic needs.
The thyroid actually expands in size by 10 percent during pregnancy, even in women with sufficient dietary iodine intake. Iodine reserves keep levels stable during pregnancy, but some women may need supplements. Circulating T4, freeT4, and thyroid-binding globulin (TBG) increase between six and eight weeks after conception.
14
As a consequence, women have lower serum TSH concentrations during pregnancy, especially during the first trimester. This is usually temporary and may be related to hCG levels. Serum TSH and the reference range gradually rise in the second and third trimesters. So the “reference ranges” used to judge test results are different during each trimester.
11
Until the fetal thyroid gland is developed, at approximately 12 weeks’ gestation, the mother’s thyroid is the only source of thyroid hormone for the baby (transferred through the placenta and amniotic fluid). If you were diagnosed with thyroid disease before you conceived, you’ll need to be monitored closely during pregnancy. If you’re hypothyroid, you’ll probably need to have your thyroid hormone dose increased by an average of 45 percent to normalize TSH. “I recommend that pregnant women with thyroiditis have their TSH checked once every six weeks,” says Mount Sinai’s Dr. Terry F. Davies.
Women being treated for hypothyroidism usually require a higher dose of levothyroxine early in the first trimester of pregnancy. An extra dose may be recommended as soon as a woman knows she’s pregnant.
11
However, TSH can also
increase
in up to 3 percent of women, so pregnancy can trigger temporary hypothyroidism and, in some cases, Hashimoto’s. Hypothyroidism during pregnancy is associated with complications including premature birth, low birthweight babies, possible miscarriage, and even later fertility problems.
11
Persistently low TSH can lead to gestational hyperthyroidism. Preexisting Graves’ may also be diagnosed for the first time during pregnancy.
So if you’re thinking of getting pregnant, thyroid hormones must be monitored. The optimal time to conceive is when you’re euthyroid.
The U.S. Preventive Services Task Force (USPSTF) and the Endocrine Society recommend that all women who are “high risk” for thyroid disease should be tested for elevated TSH, including women currently taking levothyroxine and women with a goiter or known thyroid antibodies.
15
The recommendations include not only all women over age 30 with a family history of autoimmune thyroid disease or hypothyroidism, but also women with type 1 diabetes, infertility, or a prior history of preterm delivery. Women who’ve had prior radiation therapy to the head or neck or prior thyroid surgery should also be tested.
If you’re being treated for hypothyroidism, you’ll probably need to have your thyroid hormone dose increased by an average of 45 percent to normalize TSH. According to the ATA, you may need testing every four weeks during the first half of pregnancy and at least once during weeks 26 and 32 of your pregnancy. Once you deliver, your dose of levothyroxine will be reduced to your prepregnancy level, with TSH testing done every six weeks.
11
If you have Graves’ disease and are being treated with the antithyroid drug PTU, this will continue during pregnancy. Exposure to methimazole has been associated with birth defects during the first trimester,
16
so switching to PTU is recommended.
11
Until the fetal thyroid gland is developed, at approximately 12 weeks’ gestation, the mother’s thyroid is the only source of thyroid hormone for the baby (transferred through the placenta and amniotic fluid). If you were diagnosed with thyroid disease before you conceived you’ll need to be monitored closely during pregnancy.
Untreated thyroid disease during pregnancy may negatively affect a child’s psychological development. In Graves’ disease, thyroid stimulating hormone receptor antibodies can cross the placenta and cause neonatal hyperthyroidism. Women with untreated thyroid deficiency during pregnancy may be up to four times more likely to have children with lower IQ scores, as well as deficits in motor skills, attention, language, and reading abilities, according to a landmark 1999 study from Harvard. In the study, 19 percent of the children born to mothers with undetected hypothyroidism scored 85 or lower on the IQ testing, compared to only 5 percent of children born to women without thyroid disease. (Scores below 85 typically signal that a child will have difficulty in school.)
Radioactive iodine is not given until six weeks after a woman stops breast-feeding, to make sure there’s no residual radioactivity concentrated in breast tissue.
10
Infants can develop a temporary form of
neonatal thyroid disease
, which is related to the transfer across the placenta of antibodies from the mother. It’s a rare condition that occurs in 1 to 5 percent of babies born to women with Graves’ disease. Research from Japan has found that a subset of women with autoimmune thyroiditis make what are called
TSH inhibiting antibodies
, and these antibodies can cross the placenta, resulting in transient hypothyroidism in the baby. In Graves’ disease, stimulating antibodies also cross the placenta, temporarily causing an overactive thyroid in the baby. However, all infants are routinely screened for thyroid problems.
There are no increased instances of birth defects in children born to mothers who took radioactive iodine and waited the recommended six months before becoming pregnant. Women who have trouble conceiving because of hyperthyroidism often have fertility restored after treatment.
Some women have antithyroid antibodies in their blood for years, but never develop a problem until after giving birth. Immune function is modulated during pregnancy, and the normal rebound after delivery may elevate levels of antithyroid antibodies during between three and eight months postpartum.
11
In some women, this may not produce noticeable symptoms. Others may blame their symptoms on normal fatigue, the “baby blues,” or postpartum depression. “I think thyroiditis is much more common than is reported, because a lot of postpartum depression may actually be postpartum thyroiditis,” remarks Dr. Noel Rose. And postpartum depression can be worsened by thyroiditis.
If the thyroid gland is severely inflamed, it may become overactive, causing a sudden onset of hyperthyroid symptoms. Once the thyroid hormone stored in the gland is depleted, hypothyroidism sets in. In some women, the thyroid may eventually normalize. Symptoms typically last six months or less.
11
As many as 8 to 10 percent of women may develop thyroid problems after giving birth. Radioactive iodine uptake will be low in women with postpartum thyroid inflammation; in women with Graves’ disease there will be an increased uptake of radioactive iodine due to overproduction of thyroid hormone. Before the test, breast-feeding should be discontinued for three to five days, as radioactive iodine can pass into breast milk. Having a prior episode of postpartum thyroiditis increases the risk of recurrence with each pregnancy. Women with recurrent postpartum thyroiditis have a 20 to 30 percent chance of developing permanent hypothyroidism 5 to 10 years afterward. Antithyroid antibodies may help identify women at increased risk.
The hyperthyroid phase of postpartum thyroiditis doesn’t usually require treatment, but symptoms such as palpitations and nervousness can be treated with the beta-blocker propranolol.
11
If other symptoms develop, TSH should be tested every four to six weeks.
Hypothyroidism will require replacement thyroid hormone for 6 to 12 months. If you have a goiter, it will usually shrink in response to treatment. Only tiny amounts of thyroid hormone pass into breast milk, so you can continue taking it while breast-feeding.
Hypothyroidism may become permanent after pregnancy in as many as 30 percent of women who have a preexisting problem, says Dr. Rose. So treatment is usually stopped for four to six weeks in order to do blood tests for T4 and TSH to determine whether the hypothyroidism has resolved. Women may need annual thyroid testing to see whether a thyroid problem recurs.
The ATA recommends that women experiencing postpartum depression have their thyroid hormone levels checked, since depression is associated with hypothyroidism.
11
As many as 14 percent of women will develop subclinical hypothyroidism (below clinical cutoffs) in the years just before and after menopause, mostly due to Hashimoto’s.
During perimenopause, production of estrogen and progesterone becomes erratic and may disrupt pituitary-thyroid function and even interfere with the action of thyroid hormones. Autoantibody production might also increase. “It’s really not clear what is going on. The age, sex, and postpartum distribution suggest that there’s some connection between the immune system and the endocrine system,” remarks Dr. Rose.
Hypothyroid symptoms, especially depression, may be mistakenly attributed to perimenopause or menopause, he adds. Therefore many experts say routine screening for underactive thyroid may be needed at menopause and afterward.
Menopausal women taking hormones may need an increased dose of levothyroxine. A small but important study in the
New England Journal of Medicine
in 2001 looked at the effects of estrogen therapy on pituitary-thyroid function in 11 postmenopausal women with normal thyroids and 25 women being treated for chronic hypothyroidism. In the normal women, ET produced an increase in thyroxine-binding globulin, prompting an increase in thyroxine production. But in those with hypothyroidism, there was a significant drop in the amount of free thyroxine, requiring an increased dose of medication.
An accompanying editorial suggested that in women taking thyroid hormones, thyroid function should be checked after starting ET and the dose of levothyroxine adjusted accordingly. Conversely, if a woman discontinues ET, her dose of thyroid medication may need to be reduced.
Thyroid hormone production and metabolism change during normal aging.
17
Some studies estimate that up to 16 percent of women over the age of 60 have elevated TSH (often with antithyroid antibodies), even if they don’t have symptoms of hypothyroidism.
18
One study suggested that 20 percent of these
women will develop Hashimoto’s. The risk is greatest if TSH is high and antithyroid antibodies are present.
Symptoms may be difficult to recognize in older women. Depression, dry skin, hearing loss, muscle cramps, numbness and weakness of the hands, unsteadiness of gait, anemia, and constipation may simply be blamed on aging. Hyperthyroidism can also be easily overlooked. Few of the classic symptoms, such as an enlarged thyroid, may be present in older women. Additional symptoms may include shortness of breath, palpitations, depression, nervousness, and muscle weakness.
14
Studies indicate that hypothyroidism in later life can be associated with impaired memory and concentration, as well as problems with language and “executive function,” your ability to reason, solve problems, balance your checkbook, and plan things.
13
Trouble is, those are also signs of mild cognitive impairment (MCI), a precursor to Alzheimer’s disease, and of Alzheimer’s itself. The same is true for late life depression. So experts in geriatric medicine suggest people experiencing memory problems or depression have their thyroid hormones tested as part of a medical workup. Hypothyroidism is treatable—and its cognitive and mood problems are reversible.
The risk of atrial fibrillation (AF) increases with age but is greater among women with Graves’, with AF affecting 25 to 40 percent of hyperthyroid women after age 60.
6
Because AF causes blood to stagnate and form clots leading to strokes, blood thinners (including aspirin) are usually prescribed. Beta-blockers such as propranolol are used to regulate abnormal heart rhythms. ATA guidelines recommend that older women with Grave’s disease undergo a cardiac evaluation, including an echocardiogram (ultrasound imaging of the heart), an electrocardiogram (ECG), or Holter monitoring to monitor heart rhythms over time.
10
The notion of preventing problems normally associated with aging with thyroid hormones remains controversial.
What’s not debatable is that treatment of hypothyroidism needs to be adjusted in later life. Levothyroxine is metabolized and excreted more slowly in older women, so smaller doses may be needed. Antithyroid drugs are often used before radioactive iodine treatment in older women, especially if they have other medical problems, such as chest pain (
angina
) or AF.
Radioactive iodine can trigger a temporary rise in thyroid hormone that can cause complications or heart damage. Beta-blockers may also be needed to dampen the effects of excess thyroid hormone before treatment with radioactive iodine.
All patients over age 65 need long-term follow-up with annual blood tests for TSH and T4 because thyroid function may continue to decline as years go by.
