Conditions: Chronic Lymphocytic Thyroiditis (also known as Hashimoto’s Thyroiditis)

Hashimoto’s thyroiditis is a long-lasting autoimmune condition in which the immune system attacks the thyroid gland, and it is the most common cause of an underactive thyroid.

What is chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis)?

Hashimoto's thyroiditis, also called chronic lymphocytic thyroiditis or chronic autoimmune thyroiditis, is a long-lasting condition in which the body's immune system mistakenly attacks the thyroid gland. The thyroid is a small, butterfly-shaped gland at the front of the neck that makes hormones controlling metabolism, energy, temperature, heart rate, and many other body functions.

It is the most common autoimmune disease worldwide and the leading cause of an underactive thyroid (hypothyroidism) in areas of the world with enough dietary iodine.

What is the autoimmune mechanism?

Normally, the immune system attacks only foreign invaders such as viruses and bacteria. In Hashimoto's, immune cells called lymphocytes (a type of white blood cell) build up inside the thyroid and gradually damage and destroy the hormone-producing thyroid cells. Two things drive this process:

• Immune cell attack: T-lymphocytes infiltrate the gland and directly injure thyroid cells. This cell-based attack is the main cause of thyroid destruction.

• Antibodies: B-lymphocytes within the thyroid produce antibodies against thyroid proteins, chiefly thyroid peroxidase (TPO) and thyroglobulin, two proteins the gland uses to make thyroid hormone. These antibodies are important markers of the disease, although they are more a sign of the ongoing attack than its root cause.

Over months to years, this slow, progressive destruction can leave the gland unable to make enough hormone. Some people carry thyroid antibodies for life, however, and never develop symptoms or hormone problems.

What causes Hashimoto’s thyroiditis?

Hashimoto's results from a combination of genetic susceptibility and environmental triggers. No single cause explains every case. Recognized or suspected contributors include:

• Genetic factors, including variations in immune-regulating genes (such as the HLA family)

• Changes in sex hormones, which may partly explain why women are affected more often

• Excess iodine intake, and in some settings selenium deficiency

• Viral or other infections

• Certain medications

• Exposure to radiation

• Smoking and psychological stress, which have also been studied as possible contributors

How common is Hashimoto’s thyroiditis, and who is affected?

New cases of Hashimoto’s thyroiditis occur in approximately three to six people per 10,000 population per year. Thyroid antibodies (a sign of thyroid autoimmunity) are found in roughly 10% of the general population, and estimates for Hashimoto's itself vary, with the prevalence in the overall population at least 2% and one meta-analysis reporting about 7.5%.

• Sex: women are affected far more often than men, by some estimates five to ten times as often.

• Age: it can occur at any age, including in children, but is most often diagnosed in middle age, with a peak between about 45 and 65 years.

• Family history: Hashimoto's tends to run in families, and having a close relative with thyroid autoimmunity increases the risk. Genetic makeup is estimated to account for a large share of the overall risk.

• Associated autoimmune conditions: people with Hashimoto's are more likely to have other autoimmune disorders, including type 1 diabetes, celiac disease, rheumatoid arthritis, lupus, Sjögren syndrome, Addison disease, pernicious anemia, vitiligo, and multiple sclerosis.

What symptoms and course does it have?

The course of Hashimoto's varies a great deal from person to person. Many people have no symptoms early on, and the condition is often discovered incidentally, for example when a painless thyroid enlargement or an abnormal blood test prompts further testing.

A possible early overactive phase (hashitoxicosis). In some people, inflammation damages thyroid cells and causes them to release stored hormone all at once. This can produce a temporary period of an overactive thyroid (hyperthyroidism), sometimes called hashitoxicosis. Symptoms may include a racing heartbeat, anxiety, tremor, heat intolerance, and weight loss. This phase is usually self-limited.

Progression to an underactive thyroid (hypothyroidism). As the gland's hormone stores become depleted and thyroid tissue is destroyed, many people eventually develop an underactive thyroid. Common symptoms include:

• Fatigue and low energy

• Weight gain

• Feeling cold (cold intolerance)

• Dry skin and puffy eyes

• Constipation

• Muscle aches or cramps

• Depression or low mood, slowed thinking, and poor memory

• A deeper or hoarse voice

• Heavier menstrual periods

Many of these symptoms are nonspecific and overlap with other conditions, and they do not always match the degree of thyroid dysfunction on blood tests. The progression is typically slow. In one long-term study, over half of women who started with thyroid antibodies and a mildly elevated TSH eventually developed clear hypothyroidism.

How may the thyroid look or feel?

The thyroid can change in two different directions:

• Goiter (enlargement): the classic form is a diffusely enlarged, firm gland that is usually painless, sometimes with an irregular surface. Rarely, the gland may be tender. A large goiter can occasionally press on nearby structures, causing a sense of pressure, difficulty swallowing, changes in the voice, or difficulty breathing.

• Atrophic (shrunken) gland: in other people, ongoing scarring (fibrosis) causes the thyroid to shrink and become small, without a goiter.

Hashimoto’s is typically painless, in contrast with a similar but painful condition called subacute (granulomatous) thyroiditis.

How is Hashimoto’s thyroiditis diagnosed?

Diagnosis is based on a combination of symptoms, blood tests, and imaging. A tissue sample (biopsy) is rarely needed. Thyroid size is not especially useful in making the diagnosis, since Hashimoto’s may be associated with a goiter or a normal-sized thyroid, though a diffuse, smooth, firm goiter in a young woman often prompts testing.

• TSH (thyroid-stimulating hormone): the most sensitive first blood test. A high TSH signals an underactive thyroid.

• Free T4 (thyroxine): measures the active thyroid hormone level. Results depend on the phase: TSH may be elevated with a normal free T4 (subclinical hypothyroidism) or with a low free T4 (overt hypothyroidism).

• Thyroid antibodies: elevated TPO antibodies (also called antimicrosomal antibodies) are found in the large majority of people with Hashimoto's (often reported around 90 to 95%), and thyroglobulin antibodies are elevated in a smaller share (roughly 60 to 80%). Young patients with even low levels of these antibodies are considered positive. Importantly, a minority of people with Hashimoto's, perhaps 20 to 30%, test negative for these antibodies, so normal results do not fully rule out the condition. Antibodies without hypothyroidism or a goiter are termed "suspected" Hashimoto's disease.

• Ultrasound: a painless scan that can show the characteristic patchy, uneven texture of the gland and can also detect nodules. Ultrasound and antibody testing are good at ruling out the disease when negative, but a positive result alone is not fully conclusive; combining them improves accuracy.

• Biopsy (fine-needle aspiration): not used routinely for diagnosing Hashimoto's itself, although it usually shows characteristic findings when the disease is present. It is reserved for evaluating a suspicious thyroid nodule.

• Radioactive iodine uptake scan: generally not needed to diagnose Hashimoto's. When performed, the image is characteristically a diffuse or mottled uptake in a goiter, in contrast to the focal "cold" and "hot" areas of a multinodular goiter. Areas of severely diseased thyroid replaced with scar lack uptake. The test is mainly used in other situations to help sort out the cause of an overactive thyroid, and it is not done during pregnancy or breastfeeding.

Are thyroid nodules and cancer associated with Hashimoto’s thyroiditis?

Thyroid nodules (lumps) are common and can occur along with Hashimoto's. A suspicious nodule is evaluated the same way it would be in anyone else, usually starting with ultrasound and, when warranted, a fine-needle biopsy. Two cancer-related associations are worth understanding, while keeping in mind that the absolute risk for any one person remains low:

• Papillary thyroid cancer: Hashimoto's is associated with a modestly increased likelihood of papillary thyroid cancer, the most common thyroid cancer. When it occurs in this setting, it often has a favorable outlook.

• Thyroid lymphoma: Hashimoto's is the main known risk factor for primary thyroid lymphoma. Although the relative increase in risk is substantial, this cancer is very rare overall. A rapidly enlarging thyroid mass, or nodular growth or pain in the gland, is a feature that raises this concern and typically leads to prompt evaluation.

How does Hashimoto’s thyroiditis affect pregnancy?

Thyroid hormone is essential for a healthy pregnancy and for the baby's brain development. Hashimoto's is the most common cause of an underactive thyroid during pregnancy.

• Women who are TPO-antibody positive have a higher chance of developing an underactive thyroid as pregnancy progresses, because the extra demands of pregnancy strain an already-vulnerable gland.

• Even when thyroid hormone levels are normal, thyroid antibodies have been linked to a modestly increased risk of miscarriage and preterm birth.

• Uncontrolled hypothyroidism in pregnancy is associated with complications such as high blood pressure, preeclampsia, and problems with the baby's growth and development.

For these reasons, thyroid function is monitored closely before and during pregnancy in women with Hashimoto's or thyroid antibodies. Women with Hashimoto's are also at higher risk of postpartum thyroiditis, a thyroid inflammation that can appear within a year after delivery or miscarriage.

Is treatment always needed?

Not all Hashimoto's requires treatment. A small goiter with normal thyroid function, for example, does not require therapy unless the TSH level is elevated. A very large or progressively growing gland, or hypothyroidism, is the usual reason for replacement thyroid hormone. When Hashimoto's causes an underactive thyroid, the standard treatment is a daily thyroid hormone replacement pill (levothyroxine), often taken lifelong, with periodic blood tests to adjust the dose. Treatment replaces the missing hormone rather than stopping the underlying immune process. Surgery is rarely indicated for Hashimoto's alone. See treatment of hypothyroidism and thyroid treatments.

What is the long-term outlook?

The outlook for people with Hashimoto's is generally very good. It is a manageable chronic condition. Some people never develop hormone problems and need only periodic monitoring. Those who develop an underactive thyroid can usually be treated effectively with hormone replacement and lead normal, healthy lives. Because the condition can progress slowly, can affect pregnancy, and rarely carries a small cancer risk, ongoing follow-up with a clinician is typical.