USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 42-year-old female comes to the clinic with 2 weeks cold intolerance, weight gain, constipation, and a neck mass. She also says there was a period 6 months ago where she was losing weight without even trying, so she was surprised when she began gaining it all back. She denies any fever or neck pain. Laboratory serum studies show anti-microsomal antibodies. Biopsy of the mass shows pink cells and lymphoid aggregates with germinal centers. Which of the following is the most likely diagnosis?
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.
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.
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.
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.
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.
Once there, plasma cells make antibodies against thyroid peroxidase, thyroglobulin, or TSH receptors.
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