A) Hashimoto’s thyroiditis
- What are the causes of Hashimoto’s thyroiditis?
- What are the symptoms of Hashimoto’s thyroiditis?
- Physical findings (common in hypothyroidism condition)
- Other biological disorders
- Para-clinical imaging
- Aspiration of thyroid cells
- Thyrotoxicosis and Hashitoxicosis
- Hashimoto’s thyroiditis and pregnancy
B) Other types of thyroiditis may result in hypothyroidism
- Silent subacute thyroiditis: a painless thyroiditis
- Postpartum thyroiditis (after delivery)
- De Quervain thyroiditis: a painful thyroiditis
- Thyroiditis by drug interactions
The thyroiditis means inflammation of the thyroid. Different types of thyroiditis can be distinguished. Hashimoto’s thyroiditis, the most frequent, leads in any case to a permanent hypothyroidism. The others are likely to develop, in a small percentage of cases, a permanent hypothyroidism, such as silent subacute thyroiditis, postpartum thyroiditis, De Quervain subacute thyroiditis, drug-induced thyroiditis. We will exclude from this study the acute infected thyroiditis and the Reidel thyroiditis.
A) Hashimoto’s thyroiditis
Hashimoto’s thyroiditis is a disease, and hypothyroidism is a condition. The two terms are not interchangeable. Hashimoto’s thyroiditis is one of the most common causes of hypothyroidism. It is an autoimmune disease in which the thyroid is attacked by the body’s immune system. It is this autoimmune form of hypothyroidism that is called Hashimoto’s thyroiditis. Hashimoto’s thyroiditis is sometimes called Hashimoto’s disease, autoimmune thyroiditis, or chronic lymphocytic thyroiditis. It is named after the first doctor who described this condition, Dr. Hakaru Hashimoto, in 1912.
Hashimoto’s disease is 5-10 times more common in women than in men and most often starts in adulthood (30-50 years), with a peak incidence in men occurring 10-15 years later. The prevalence (number of cases) increases with age.
What causes Hashimoto’s disease?
Immune dysregulation is another term for autoimmune disease. It is not known specifically what causes Hashimoto’s disease and what causes the body’s immune system to suddenly see the thyroid as a foreign object and begin an attack. Most researchers agree that:
● Low iodine (as well as certain minerals such as selenium, zinc, and iron) can lead to inflammation of the thyroid.
● Hashimoto’s disease can be genetic. It sometimes occurs among members of the same family. Thus, if your mother, grandmother, or aunt has Hashimoto’s disease, you are more likely to develop the disease. And Hashimoto’s disease is associated with other autoimmune conditions such as type 1 diabetes, and celiac disease. That means that patients who have been diagnosed with autoimmune disorder are also at greater risk to have others, including Hashimoto’s disease.
● A drastic change in sex hormone levels during pregnancy and menopause may also be a predisposing factor for the development of Hashimoto’s disease, due to the then increased immune system activity.
● Intestinal permeability may play a part in Hashimoto’s disease. 60 – 70% of the immune system is located in the gut as a vast network of lymph tissue.
● Gluten can also trigger the autoimmune reaction that causes Hashimoto’s disease. I will come back to that.
● Chronic viral infections (Epstein Barr virus, Cytomegalovirus, Human Herpes Virus-6) and chronic bacterial infections (Borrelia, mycoplasma, chlamydia, and others), creating an immune dysfunction, may cause Hashimoto’s disease, as well as other autoimmune diseases, often also associated with Hashimoto’s disease. I will discuss that later.
● The accident of the reactor of Tchernobyl may be another cause of Hashimoto’s disease.
What are the symptoms of Hashimoto’s thyroiditis?
The symptoms are similar to those of hypothyroidism in general, with variable degrees. Some patients manifest no symptoms, or hardly any symptoms and no one specific. This subclinical hypothyroidism, with a thyroid gland normal in size, may be found simply from routine screening of thyroid function. For others, the thyroid becomes enlarged, a condition known as a goiter, which varies from small to large. 20 to 50 % of women with Hashimoto’s disease present initially with a goiter. Patients with a large goiter may feel discomfort in the neck area and/or the throat, even sore or tender. Less commonly, swallowing or even breathing can become difficult.
Hypothyroidism is usually insidious in onset, with signs and symptoms slowly progressing over months to years, due to a slow but steady destruction of the gland that eventually results in the thyroid’s inability to produce sufficient thyroid hormone – the condition known as clinical (overt) hypothyroidism. TSH usually is high, free T4 and T3 are usually low. But again, I should insist that “normal” thyroid tests do not exclude thyroid failure. Sometimes, only the presence of high levels of anti-thyroid antibodies would demonstrate a failure process underway, but must they have been measured in a systematic way, which is almost never the case (and never as a second-line when a routine thyroid test was “normal”). Yet, as I say when I give a lecture on the subject, it is easier to ask antibodies, and less risky, than go and ask the phone to a girl you like but walking on the sidewalk opposite.
Physical findings (common in hypothyroidism condition)
It seems useful to describe the possible findings by the physician during the clinical examination:
● The thyroid gland is typically enlarged, firm, and rubbery. It may be normal in size or not palpable at all
● Puff face and periorbital edema typical of hypothyroid faces
● Cold, dry skin
● Peripherial edema of hands and feet, typically nonpitting
● Thickened and brittle nails
● Hair loss involving the scalp and the lateral third of the eyebrows. In Hashimoto’s thyroiditis, hair loss is thought to involve an autoimmune process directed against the hair follicles
● Bradycardia (low heart rate)
● Normal or low blood pressure (sometime diastolic hypertension)
● Diminished deep tendon reflexes
● Macroglossia (enlarged tongue)
● Voice hoarseness
● Slow speech
● Impairment in memory function
● Peripheral neuropathy – this may be a mono-neuropathy, such as a carpal tunnel
syndrome or a polyneuropathy resulting from the involvement of several peripheral nerves.
● Chronic urticarial (reported more frequently in patients with Hashimoto’s thyroiditis) (Click Here)
Other laboratory finding
♦ Complete blood count: up to 30-40% of patients with hypothyroidism have anemia, usually from decreased erythropoiesis (red blood cells formation process), but it can also due to deficient of iron, vitamin B-12, or folic acid intake.
♦ Total cholesterol, LDL (low-density lipoprotein), and triglycerides levels may be elevated.
♦ Prolactin may be elevated. This can lead to decrease the GnRH activity (gonadotropin-releasing hormone), and thus, decreased synthesis and secretion of gonadotropin hormones (FSH and LH). The result of this is menstrual abnormalities, anovulatory cycles, galactorrhea, and infertility in some patients.
Para-clinical imaging
They are used in conjunction with physical examination of the thyroid, when the size and shape of the gland needs to be evaluated (enlargement, nodules, lumps).
► Thyroid Ultrasound
► CT scan, known as computed tomography or “cat scan”.
► Radioactive Iodine Uptake (RAI-U): it can help tell whether a person has thyroiditis, toxic multi-nodular goiter, or Graves’ disease. A thyroid that takes up iodine is considered “hot” or overactive, as opposed to a “cold” or underactive thyroid. In Graves’ disease (hyperthyroidism), RAI-U is elevated, and the entire gland becomes “hot”. In Hashimoto’s thyroiditis, the uptake is usually low (“cold”) with patchy hot spots in the gland.
► MRI – Magnetic Resonance Imaging: it doesn’t require any injection of contrast dye or radiation.
Cellular Aspiration of The Thyroid
The pathologist with a fine needle aspiration cytology (FNAC) will identify Hurthle cells which accurately diagnose Hashimoto’s thyroiditis in most patients (92%).
Thyrotoxicosis and Hashitoxicosis
We have described the pattern when Hashimoto’s runs its normal course.
However, at some stage of Hashimoto’s disease, and in particular, often during the early stages, the thyroid that is in the process of autoimmune failure may actually spurt into action and become temporarily overactive, making a person hyperthyroid. This condition is influenced by the rapidity of onset and the severity of the clinical state of hypothyroidism. This happens when the autoimmune process damages the follicles of the thyroid gland enough for them to rupture (Click Here). The follicles contain thyroid hormone, and when they rupture, the hormone leaks into the blood. The leakage can be so great that the patient’s tissues are exposed to too much thyroid hormone, and this causes thyrotoxicosis (characteristic of hormone overstimulation) with symptoms of hyperthyroidism. Fortunately, in most cases, the leakage is time-limited, and because of that, the thyrotoxicosis is transient.
Sometimes, it is the temporary hyperthyroidism symptoms that first bring a Hashimoto’s patient to the doctor, such as anxiety, insomnia, weakness, heart palpitations, tachycardia (fast pulse), restlessness with hand or leg tremor (shaking), muscle weakness, weight loss despite increased appetite, diarrhea, insomnia, heat intolerance, excessive sweating, skin warmth and moistness, high blood pressure. Quite opposite symptoms of hypothyroidism. Together with swelling of the thyroid gland, leading to a feeling of tightness or fullness in the throat and discomfort swallowing and breathing due to the enlargement of the thyroid. TSH is low (sometimes dramatically low), free T4 and free T3 are high, characteristic of hyperthyroidism. The problem is that the patient doesn’t suffer from Graves’ disease, his hyperthyroidism is just temporary thyrotoxicosis, and the patient is ultimately on his or her way to becoming hypothyroid.
If patients with autoimmune thyroiditis may go through only one phase of thyrotoxicosis, they may keep vacillating between hypo and hyperthyroid phases, known as hashitoxicosis.
Hashitoxicosis
This is not a very common situation. Patients keeping on going back and forth between hypothyroid and hyperthyroid can cycle very quickly in between the both. It could be a few times per day at its worse, or cycling every 4 to 5 days or more. Sometimes the hyper portion lasts longer and other times the hypo portion lasts longer.
So, for example, periods of anxiety, diarrhea, loss of weight, sweating, rise of blood pressure, heart palpitations and tachycardia, increased body temperature, will be followed by periods of depression, constipation, gain of weight, blood pressure and heart rate in normal range or low, feeling cold, low body temperature. The thyroid gland will also see the appearance oscillation: to an enlarged, firm to the touch and painful thyroid, will succeed a smaller thyroid, painless, with swallowing and breathing resuming a normal course, if they had been disturbed. Before a new hyperthyroidism cycle begins.
The hyperthyroid phase of Hashimoto’s thyroiditis mimics technically Graves’ disease. The difference between Hashimoto’s and Graves’s is that Hashimoto’s can fluctuate between hypo and hyper, while Graves’s disease is strictly hyperthyroidism.
Hashitoxicosis Labs [Source: Elaine Moore: March, 2006″ Thyroid Disease Triggers”]
● The anti-thyroid peroxidase and anti-thyroglobulin antibodies, which are associated with thyroid cell inflammation, are found in Hashimoto’s thyroiditis, in hashitoxicosis and Graves’ disease.
● The immune-globulins that stimulate the TSH receptor (TSI antibodies), markers of Graves’ disease, are also present in hashitoxicosis.
● In Graves’ disease, the anti-TSH receptor antibodies are present at a lower rate than the specific markers (TSI) of the disease. In hashitoxicosis, the anti-TSH receptor antibodies meet at higher rates than the TSI antibodies.
The antibody levels are not always useful to distinguish between the diagnosis of hashitoxicosis and Graves’ disease, especially as their characteristics can strongly overlap. The color Doppler ultrasound can clearly distinguish between Graves’ disease with a thyroid whose vascularization is greatly increased, whereas it is normal or slightly increased in Hashimoto’s thyroiditis.
Hashimoto’s Thyroiditis And Pregnancy
Hashimoto’s thyroiditis is not a reason to avoid pregnancy. However, most women with Hashimoto’s thyroiditis do have trouble conceiving.
If your doctor has told you that you have tested positive for thyroid antibodies but you have a normal TSH, what does that mean? Usually, it indicates that your thyroid is in the process of autoimmune failure. Not failed yet, and not failed enough to register in the standard TSH thyroid test, but in the process of failing.
Antibodies alone can cause thyroid-related symptoms, and have been shown to affect fertility or the ability to maintain a pregnancy.
An article in the Journal of Clinical Endocrinology and Metabolism, August 1997 states, “the risk of miscarriage is twice as high in women who have anti-thyroid antibodies than in those who do not…” and Obstetrics and Gynecology 1997 Volume 90:364-369, states, “the risk of miscarriage is higher when a woman is positive for anti-thyroid microsomal antibodies [anti-TPO]…”.
Women with a personal or family history of thyroid disorders, or suffering from other autoimmune diseases, should be screened for thyroid antibodies before conceiving.
The other issue is the THS levels itself. According to endocrinologists, a woman with evidence of thyroid disease will find it hard to get and/or maintain a pregnancy if her TSH level is higher than 2 mIU/L, optimally between 1 and 2.
B) Other types of thyroiditis that may lead to hypothyroidism
1) Silent subacute thyroiditis: a painless thyroiditis
It was not recognized until the 1970’s. The typical course of painless thyroiditis is a temporary acute phase of hyperthyroidism that will end within 3 months, with increased blood levels of thyroid hormones T3 and T4, and decreased radioactive iodine uptake. Many patients with painless thyroiditis have high serum concentrations of anti-thyroid peroxidase and anti-thyroglobulin antibodies, many have a family history of thyroid auto-immune disease. The thyroid does not become enlarged, or slightly. The needle biopsy resembles Hashimoto’s thyroiditis with lymphocytes. Painless thyroiditis is considered a variant form of Hashimoto’s thyroiditis. It is rarer than Hashimoto’s.
The hyperthyroidism phase, due to leaking hormones stocked in the inflamed thyroid, is sometimes followed by a period of hypothyroidism, as damage continues, and then a return to normal thyroid function. Generally (80 % of the cases), silent thyroiditis will go away on its own within 1 year. The remaining 20 % become permanently hypothyroid and will need thyroid hormone replacement.
2) Postpartum thyroiditis
The exact cause in not known but it is believed to be an auto-immune disease very similar to Hashimoto’s thyroiditis. In fact, these two disorders cannot be distinguished from one another. It occurs in approximately 5 to 10% of women after delivery. The incidence can be greater in certain high risk populations, such as any woman with:
- Autoimmune disorders (such as Type 1 Diabetes Mellitus)
- Anti-thyroid antibodies: women with positive anti-thyroid antibodies are at a much higher risk of developing postpartum thyroiditis than women who do not have positive antibodies (risk correlates with antibodies levels: the higher the antibody the higher the risk)
- Personal history of previous thyroid dysfunction
- History of previous postpartum thyroiditis (20% of women will have recurrence of thyroiditis with subsequent pregnancies)
- Family history of thyroid dysfunction
Postpartum thyroiditis is a lymphocyte subacute auto-immune thyroiditis with symptoms and signs similar to silent/painless thyroiditis, and increased concentrations of thyroid antibodies. It is believed that women who develop postpartum thyroiditis have an underlying asymptomatic autoimmune thyroiditis that flares in the postpartum period when there are fluctuations in immune function.
If postpartum thyroiditis is classically characterized by hyperthyroidism (thyrotoxicosis), followed by hypothyroidism, not all women demonstrate evidence of going through both phases. Approximately 1/3 of patients will manifest both phases, 1/3 of patients will have only a thyrotoxic phase, and 1/3 only a hypothyroid phase.
The thyrotoxic phase occurs 1-4 months after delivery, lasts for 1-3 months (such as silent/painless thyroiditis) and is associated with symptoms including anxiety, insomnia, palpitations and tachycardia, fatigue, weight loss, irritability, shakes and tremors. Since these symptoms are often attributed to being postpartum and the stress of having a baby, the thyrotoxic phase of postpartum thyroiditis is often missed. It is much more common for women to present in the hypothyroid phase, which typically occurs 4-8 months after delivery and may last up to 9-12 months. Typical symptoms include fatigue, weight gain, constipation, dry skin, depression and poor exercise tolerance.
Most women will have return of their thyroid function to normal within 12-18 months of onset of symptoms. However, approximately 20% of those that go into a hypothyroid phase will remain hypothyroid.
3) De Quervain’s thyroiditis: a painful thyroiditis
It is also called subacute or granulomatous thyroiditis. It was first described in 1904 and is much less common than Hashimoto’s thyroiditis. It is characterized by a thyroid gland which swells rapidly, the goiter is diffused, firm, very painful and tender, along with impressive signs of systemic inflammation, such as high fever, generalized malaise, very high sedimentation rate with leukocytosis. Some patients experience difficulty swallowing. The subacute painful De Quervain thyroiditis may start in one thyroid lobe, and pain can radiate in the neck, jaw and ear. The disease breaks out often after an upper respiratory tract infection, it is why a viral origin is suspected but never confirmed. Unlike the lymphocyte auto-immune thyroiditis, as just described, histology of De Quervain thyroiditis shows granulomas with giant epithelial cells, and, biologically, thyroid antibodies are not present in the blood. This hyperthyroid phase (because the gland discharges thyroid hormones in the blood), which generally resolves over the next several weeks, is followed by a hypothyroid phase that last several months. Nearly all patients recover and the thyroid gland returns to normal. A few patients (5 %) will become permanent hypothyroid.
4) Thyroiditis by drug interactions
Thyroiditis can be seen with drug interactions such as amiodarone, interferon’s alpha and beta, interleukine-2, and lithium (Click Here).