Graves disease

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 common 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.

The circulating T cells bind to the follicular cells and infiltrate into the interstitium of the thyroid tissue - the space between follicular cells.

Third, it turns out that the fibroblasts in the tissue around the eyes and in the skin also get stimulated by thyroid-stimulating antibodies, and they start to multiply and make extracellular matrix proteins called glycosaminoglycans which build up in the tissues over time.

The symptoms of Graves disease can be summed up with the triad of hyperthyroidism, ophthalmopathy, and dermopathy. Thyroid-stimulating immunoglobulins target and activate the TSH receptor causing goiter which is the term used to describe an enlarged thyroid - because of the hypertrophy and hyperplasia of the gland; weight loss despite an increase in appetite because of the higher basal metabolic rate; heat intolerance because the body is producing more heat; and rapid heart rate, sweating, hyperactivity, anxiety and insomnia because of the effect of thyroid hormones on the sympathetic nervous system.

The build up of glycosaminoglycans causes local inflammation and swelling around the eyes - called Graves ophthalmopathy.

The ophthalmopathy causes exophthalmos, or outward bulging of the eyeball; weakens the muscles that control eye and upper eyelid movements; and can damage the cornea over time because exophthalmos can dry out the eyes and increase the risk of corneal ulcers.

Pretibial myxedema, caused by the glycosaminoglycan build up, can lead to non-pitting edema - or swelling - and skin thickening, usually over the shins.

Thyroid storm, a life-threatening complication of hyperthyroidism where the body goes into a state of severe hypermetabolism, can develop when someone with hyperthyroidism stops their treatment, develops an infection, or has surgery.

All of the normal symptoms of hyperthyroidism become exaggerated - for example heat intolerance turns to high fever and rapid heart rate turns to cardiac arrhythmia.

Individuals with Graves disease will also more likely to develop other autoimmune conditions, like rheumatoid arthritis or diabetes mellitus type 1.

Diagnosing Graves disease involves measuring blood levels of TSH, as well as T3, and T4. Measuring thyroid-stimulating antibodies will confirm Graves disease as the cause of the hyperthyroidism.

Radioiodine scans and measurements of iodine uptake can also support the diagnosis. Graves disease is mostly treated using medication, like beta-blockers to treat the immediate symptoms of hyperthyroidism, and anti-thyroid drugs to block thyroid hormone production and release.

Radioiodine therapy can be used for partially or completely destroy thyroid function, followed by replacement hormone therapy.

In cases where large goiter is compressing surrounding tissues, surgery is used to remove the thyroid. Graves ophthalmopathy usually needs separate treatment, which can include steroids, radiation therapy, and surgery.

All right, as a quick recap, Graves disease is an autoimmune disease where the body produces autoantibodies, including thyroid-stimulating immunoglobulins, which causes excess production of thyroid hormones.

It affects follicular cells in the thyroid and in fibroblasts around the eyes and in the skin, and the result is hyperthyroidism, ophthalmopathy, and dermopathy.

It affects follicular cells in the thyroid and in fiberglass around the eyes and in the skin and the result is hyperthyroidism off the