First described by Irish surgeon Robert James Graves, Graves disease is an autoimmune disorder that causes hyperthyroidism.
In hyperthyroidism, ‘hyper’ refers to having too much, and ‘thyroid’ refers to thyroid hormone, so Graves disease refers to a condition where there’s excess thyroid hormones.
Normally, the hypothalamus, which is located at the base of the brain, detects low blood levels of thyroid hormones and releases thyrotropin-releasing hormone into the hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary.
The anterior pituitary then releases thyroid-stimulating hormone, also called 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”.
The thyroid gland is made up of thousands of follicles, which are small spheres lined with follicular cells.
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 hungry predator or to stay warm during a snowstorm!
Now, in Graves disease, the trigger is unclear, but for some reason the B cells start to produce a few different types of antibodies against thyroid proteins.
The most antibody is the thyroid-stimulating immunoglobulin, which binds to the TSH receptor on thyroid cells, imitating TSH, and stimulating the thyroid cells to release more T3 and T4. But the effects of thyroid-stimulating immunoglobulins can also directly affect certain tissues.
First, there’s thyroid hypertrophy, meaning growth in the interstitium of the tissue, and there’s hyperplasia, meaning an increased number of follicular cells, both of which causes the thyroid to enlarge.
The follicle cells also change shape - becoming taller than in a healthy thyroid as they crowd together.
Second, in response to the thyroid-stimulating antibody, the follicular cells also start to express molecules on their surface that attract nearby T cells.
