Hashimoto thyroiditis

Definitions & Key takeaways

Hashimoto thyroiditis is a type of autoimmune disease that attacks and destroys the thyroid gland. This can cause hypothyroidism, which can lead to a wide range of symptoms, such as tiredness, weight gain, depression, and changes in your menstrual cycle. The cause of hashimoto's thyroiditis is unknown, but it's thought to be caused by a combination of genetic and environmental factors.

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Introduction0:00–0:41

Hashimoto’s thyroiditis, named after the Japanese physician Hakaru Hashimoto who first described it, belongs to a group of disorders where there’s some form of inflammation “-itis” of the thyroid gland.
It’s basically an autoimmune destruction of the thyroid gland, which typically progresses gradually to hypothyroidism, or state of too low “hypo-“ thyroid hormones.
In fact, Hashimoto’s thyroiditis is the most common cause of hypothyroidism in areas of the world where dietary iodine, the basic structural element of thyroid hormones, is sufficient.

Physiology0:41–3:52

Normally, the hypothalamus, which is located at the base of the brain, secretes thyrotropin-releasing hormone, or ΤRH, into the hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary.
The anterior pituitary then releases a hormone of its own, called thyroid-stimulating hormone, thyrotropin or simply TSH.
TSH stimulates the thyroid gland which is a gland located in the neck that looks like two thumbs hooked together in the shape of a “V”.
If we zoom into the thyroid gland, we’ll find thousands of follicles, which are small hollow spheres whose walls are lined with follicular cells, and are separated by a small amount of connective tissue.
Follicular cells convert thyroglobulin, a protein found in follicles, into two iodine-containing hormones, triiodothyronine or T3, and thyroxine or T4.
Once released from the thyroid gland, these hormones enter the blood and bind to circulating plasma proteins. Only a small amount of T3 and T4 will travel unbound in the blood, and these two hormones get picked up by nearly every cell in the body.
Once inside the cell T­4 is mostly converted into T3, and it can exert its effect. T3 speeds up the basal metabolic rate.
So as an example, they might produce more proteins and burn up more energy in the form of sugars and fats. It’s as if the cells are in a bit of frenzy.
T3 increases cardiac output, stimulates bone resorption - thinning out the bones, and activates the sympathetic nervous system, the part of the nervous system responsible for our ‘fight-or-flight’ response.
Thyroid hormone is important - and the occasional increase is like getting a boost to fight off a zombie or to stay warm during a snowstorm!
Thyroid hormones are also involved in a number of other things, like controlling sebaceous and sweat gland secretion, hair follicle growth, and regulating proteins and mucopolysaccharide synthesis by skin fibroblasts.
For all this to work properly, the levels of thyroid hormones have to stay within the normal range. To do that, the body uses negative feedback, which means that low levels of thyroid hormones tell the hypothalamus and pituitary gland to increase their secretion of TRH and TSH, respectively.
More TRH increase TSH production in the pituitary and the thyroid gland gets more stimulation to make thyroid hormones, and eventually, T3 and T4 levels go back up to the normal range again.
However, whenever there’s increased TRH, the pituitary gland also gets stimulated to produce more prolactin, whose job is to stimulate breast milk production and inhibit ovulation, which is when an egg cell is released from the ovary, and inhibit spermatogenesis, which is the development of sperm cells.

Causes3:52–5:16

Now, Hashimoto’s thyroiditis is an autoimmune disease, meaning that the immune system goes rogue and starts attacking our own follicular cells in the thyroid.
The exact trigger for this response is unknown, but there does seem to be a genetic component. For example, mutations in specific human leukocyte antigen genes called HLA-DR3 and HLA-DR5 are associated with developing Hashimoto’s thyroiditis.
Due to these susceptibility genes, immune cells sometimes are not “clever” enough, so they are not “clever” enough and confuse normal antigens from the thyroid gland with antigens of foreign invaders like viruses, simply because they look similar.
This process is called molecular mimicry, because from the perspective of the immune cells, a host protein is mimicking a foreign protein.
When our own proteins triggers an immune response, that protein is called an autoantigen. So, these autoantigens get picked up by antigen- presenting cells, and get carried to a nearby lymph node to activate CD4+ T-helper cells.
T-helper cells stimulate the B- cells in the lymph node to start proliferating and differentiate into plasma cells, which produce specific auto-antibodies against these self- antigens.

Pathology5:16–8:02

In Hashimoto’s thyroiditis, these plasma cells and T- helper cells enter the circulation and reach the thyroid gland. Once there, plasma cells make antibodies against thyroid peroxidase, thyroglobulin, or TSH receptors.
These autoantibodies bind to and block those targets which gets in the way of normal thyroid function. In addition, they act like a “tag” on the follicular cells that have these proteins, so that they can be targeted and destroyed by natural killer, or NK cells.
Meanwhile, CD4+ T-helper cells produce inflammatory cytokines, like interferon-γ, which attract macrophages into the thyroid gland which then cause damage to the follicles.
These cytokines also attract another type of T- lymphocytes, called CD8+ cytotoxic T-cells. CD8+ cytotoxic T-cells directly target and destroy thyroid follicular cells.
Initially, the destruction of follicular cells leads to T3 and T4 getting spilled out into the blood, creating a transient hyperthyroid or thyrotoxic state, often called “hashitoxicosis” but as the thyroid gland gets more and more damaged, thyroid hormones diminish.
The hypothalamus and pituitary gland respond by increasing their TRH and TSH production, but eventually, the thyroid becomes too damaged to produce enough thyroid hormones.
Long term inflammation causes follicular cells to change into what are called Hurthle cells which are enlarged cells with an eosinophilic, or pink and granular cytoplasm.
Meanwhile, the colloid gets depleted and follicles atrophy, or simply get smaller. What forms in-between them are clusters of lymphocytes, particularly B- cells, called germinal centers.
These germinal centers form outside of lymph nodes where they’re usually found and are in the thyroid gland tissue itself.
In rare situations, these B-cells may turn cancerous, giving rise to a B- cell lymphoma of the thyroid gland. In any case, though, all this chronic inflammation also causes connective tissue to build up around these atrophic follicles.
This increased amount of connective tissue along with the extensive immune cell infiltration causes the gland to enlarge.
In other words, as the disease progresses, the thyroid gland consists of more and more immune cells and connective tissue, and less functioning thyroid cells.

Symptoms8:02–9:46

Symptoms of Hashimoto’s thyroiditis usually start in the hypothyroid phase and are directly related to the low T3 and T4 levels.
Individuals often have a goiter, meaning that their thyroid is enlarged and sometimes has nodules, or lumps, which can sometimes press on the trachea, causing voice hoarseness, or on the esophagus, causing difficulty swallowing.
The decreased metabolic rate could cause individuals to get tired easily, feel weak and cold, have constipation, and rapid weight gain even without any change in diet or exercise.
Typically the heart rate and respiratory rate slow down as well. The skin can become dry and rough, because there’s less sweat secretion, and the hair and nails can become brittle and sometimes fall off.
Εlevated prolactin levels from the increased thyrotropin-releasing hormone could also cause problems like menstrual abnormalities and galactorrhea, which is a milky nipple discharge, as well as infertility.
In severe cases, myxedema develops, meaning that there’s increased deposition of various proteins and mucopolysaccharides in the upper skin layers, leading to edema or swelling, in particular around the eyes, hands and feet.
Finally, in the rare case of a thyroid lymphoma, there’s an extremely fast- growing goiter, which compresses the trachea and the esophagus even more.
Sometimes, this lymphoma might also spread to the nearby lymph nodes, causing them to enlarge, or to various other organs all over the body, such as the lungs and the liver.

Diagnosis9:46–10:12

Diagnosis of Hashimoto’s thyroiditis is usually based on a combination of low serum levels of free thyroid hormones and increased TSH levels with high levels of the associated autoantibodies, mainly anti-thyroid peroxidase and antithyroglobulin antibodies.
Fine- needle aspiration should be used to get a biopsy, when thyroid lymphoma is suspected. Treatment of Hashimoto’s thyroiditis typically requires lifelong thyroid hormone replacement, mainly with levothyroxine.

Treatment10:12–10:32

For individuals with a very large goiter compressing the airways or the esophagus, or if there’s suspicion of a lymphoma, then surgical removal may be needed.

Review10:32–10:45

All right, as a quick recap, Hashimoto’s thyroiditis is an autoimmune disorder in which the thyroid gland is gradually destroyed resulting in hypothyroidism and an increased risk of thyroid cancer.