Subacute granulomatous thyroiditis

Definitions & Key takeaways

Subacute granulomatous thyroiditis is a self-limited inflammatory condition of the thyroid gland that commonly occurs after an upper respiratory tract infection. It presents as a transient, painful enlargement of the thyroid gland, which can sometimes press on the esophagus, causing dysphagia. There can also be hyperthyroidism signs, like feeling hot and sweating excessively, diarrhea, and rapidly losing weight even without any change in diet or exercise. In rare cases, there may be progression to a hypothyroid state, with symptoms of a decreased metabolic rate like feeling cold and weak, developing dry and rough skin, having constipation, and rapidly gaining weight without any change in diet or exercise. Subacute granulomatous thyroiditis generally resolves on its own, and treatment is supportive care with pain medications, such as nonsteroidal anti-inflammatory drugs.

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Subacute granulomatous thyroiditis, also known as De Quervain’s thyroiditis, belongs to a group of disorders with inflammation “-itis” of the thyroid gland.
This inflammation is “granulomatous”, meaning there are aggregations of immune cells, mainly activated macrophages, that form tiny nodules within the thyroid gland.
Subacute implies that it’s somewhere between acute and chronic, typically developing after an acute event, like a viral infection.
Normally, the hypothalamus, which is located at the base of the brain, secretes thyrotropin-releasing hormone, known as 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 can be really useful when you need a boost to get through the final rounds of a sporting competition or to stay warm during a snowstorm!
Meanwhile, thyroid hormones are involved in a number of other things, such as normal function of sebaceous and sweat glands, growth of hair follicles and regulation of the synthesis of proteins and mucopolysaccharides by skin fibroblasts.
Now, subacute granulomatous thyroiditis is typically triggered by a viral infection of the upper respiratory system, for example, adenovirus, mumps, measles or coxsackievirus.
Sometimes, these viruses spread to the thyroid gland and target the thyroid cells. And when they get in and infect these cells, they can cause the thyroid cells to present weird and abnormal proteins on their MHC class 1 molecules.
Soon, immune cells, particularly CD8 positive T cells and antigen- presenting cells, like macrophages, rush into the thyroid tissue.
When the CD8 positive T cells identify the abnormal proteins on the MHC class 1 molecules, they typically destroy the thyroid cells.
As these thyroid cells die, they spill out viral antigens, as well as some of their own cellular antigens, like thyroid peroxidase, thyroglobulin, or TSH receptors.
And while macrophages try to clean away those viral remnants, they sometimes pick up the thyroid antigens as well. Next, these macrophages carry both viral and thyroid self- antigens to a nearby lymph node to activate CD4+ T-helper cells.
T-helper cells secrete inflammatory cytokines, like interferon- γ, which help activate more macrophages. Meanwhile, other cytokines, like interleukin-2 stimulate the B-cells in the lymph node which makes them proliferate and differentiate into plasma cells, which produces not only specific antibodies against the virus, but also autoantibodies against those self-antigens.
Now, all of these antibodies as well as the activated macrophages, enter the circulation and reach the thyroid gland. Once there, some of these antibodies target the viral- infected cells, but some also bind to thyroid peroxidase, thyroglobulin, or TSH receptors of the surrounding healthy cells.
These autoantibodies not only block normal thyroid function, but also “tag” the follicular cells for further destruction by activated macrophages.
Some of the macrophages join together to form giant cells with multiple nuclei, which is why sometimes this condition is called “giant cell thyroiditis”.
Often, these activated macrophages, either as single cells or as multinucleate giant cells, along with some lymphocytes, organize themselves into granulomas.
These are basically small aggregates of macrophages, surrounded by giant cells and a rim of lymphocytes. Ultimately, the result is that the thyroid gland ends up getting simultaneously destroyed both by the virus as well as by its own immune cells.
At first, as the follicles get destroyed, T3 and T4 spill out into the blood, creating a transient hyperthyroid or thyrotoxic state.
Excess T3 and T4 reaches every cell in the body and speeds up its metabolism. Because of the high levels of T3 and T4, the pituitary gland decreases its TSH production.
The good thing is this process is self-limited in most cases, meaning that as soon as the viral infection is over, inflammation subsides on its own, so the thyroid follicles start repairing themselves and restoring their normal function.
This might take six to eight weeks or a bit longer, but recovery is nearly always complete. In rare cases, the damage can’t be repaired.
In those situations, the loss of thyroid tissue causes a hypothyroid state. Symptoms of subacute granulomatous thyroiditis usually begin several days to few weeks after a viral illness, such as pharyngitis.
The most prominent sign is an enlarged painful thyroid gland, which can sometimes press on the esophagus, causing dysphagia - difficulty swallowing.
During the hyperthyroid or thyrotoxic state, the increased metabolic rate could cause individuals to feel hot and sweat a lot, have diarrhea, and rapidly lose weight even without any change in diet or exercise.
After about 6 to 8 weeks, thyroid function typically goes back to normal, so symptoms disappear completely. In the rare cases of a progression to a hypothyroid state, the decreased metabolic rate causes a person to feel cold and weak, develop dry and rough skin, have constipation, and rapid weight gain without any change in diet or exercise.
Diagnosis of subacute granulomatous thyroiditis is usually based on seeing an initial hyperthyroid phase, where Τ3 and T4 are high and TSH is low, while these most commonly go back down to normal or rarely progress to a hypothyroid phase with low Τ3, T4 and high TSH.
Inflammatory markers like erythrocyte sedimentation rate and C-reactive protein are also typically elevated. Since subacute granulomatous thyroiditis generally resolves on its own, treatment requires supportive care, with pain medications, such as nonsteroidal anti-inflammatory drugs.
But close monitoring with thyroid function tests is important, so that if hypothyroidism develops, thyroid hormone supplements can be administered.
All right, as a quick recap, subacute granulomatous thyroiditis is a self- limited inflammatory condition of the thyroid gland that commonly occurs after an upper respiratory tract infection.
It presents as a transient, painful enlargement of the thyroid gland with hyperthyroid signs and rarely progresses to hypothyroidism.