Hyperthyroidism is the state of a hyperfunctioning thyroid gland commonly referred to as an overactive thyroid gland. In this state, the thyroid gland produces and secretes excessive quantities of thyroid hormones (thyrotoxicosis). Hyperthyroidism is due to a number of causes but over 70% of the cases are a result of Graves disease.
What is Graves disease?
Graves disease is an autoimmune condition that causes overactivity of the thyroid gland (hyperthroidism). In Graves disease, the body produces antibodies that target its own tissues (autoantibodies), specifically the thyroid gland. These autoantibodies attach to the same receptor sites that are occupied by the hormone that stimulates the thyroid gland. As a result the overactive thyroid gland produces excessive amounts of thyroid hormones thereby leading to the associated clinical syndrome (thyrotoxicosis).
The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), control the body’s metabolism. The thyroid gland’s activity is regulated directly by the anterior pituitary (pituitary gland) and indirectly by the hypothalamus. When the thyroid gland is needed to produce and secrete more thyroid hormones, the hypothalamus releases thyrotropin-releasing hormone (TRH). The degree of stimulation is determined by the quantity of thyroid hormones in the bloodstream. TRH acts on the anterior pituitary causing it to secrete thyroid stimulating hormone (TSH). By traveling through the bloodstream, TSH reaches the thyroid gland where it binds to hormones on the thyroid follicular cells. These cells are then stimulated to produce the thyroid hormones that are temporarily stored in the thyroid gland and then released into the circulation.
Causes of Graves Disease
In Grave’s disease, the autoantibodies known as thyroid-stimulating immunoglobulins (TSIs) and specifically the thyrotropin-receptor antibody (TRAb) mimic the action of thyroid stimulating hormone (TSH). Other related immunoglobulins seem to have little effect in thyroid gland activity.
Since these autoantibodies are not regulated in the way TSH is by TRH, the continuous stimulation of the thyroid gland leads to an excess of thyroid hormones. Furthermore, TSIs are long acting, stimulating the thyroid gland for up to 12 hours whereas TSH are short acting only stimulating the gland for an hour or so. These antibodies are formed by activated B-lymptocytes which are immune cells that are meant to protect the body from invading pathogens.
Graves disease appears to be a combination of genetic and environmental factors although the exact cause is unknown. It is believed that a viral infection may trigger the development of the thyroid-stimulating immunoglobulins (TSIs) as a result of genetic susceptibility. These genes code for the autoantibodies and it is possible that it may be activated by other mechanisms that are unrelated to a preceding infection. It may also be possible that the similarity of the viral antigen to the thyrotropin receptor leads to the antibodies incorrectly attaching to the receptor.
Signs and Symptoms of Graves Disease
The clinical features are similar to that of hypothyroidism as discussed under signs and symptoms of thyroid overactivity. Briefly this includes :
- Intolerance to heat
- Weight loss despite normal to increased appetite
- Excessive sweating
- Rapid heart rate (tachycardia) with or without irregularity
- Enlarged thyroid gland (goiter)
- Menstrual changes
- Thinning hair
A characteristic set of eye signs and symptoms known as Graves’ opthamology is an important consideration in the clinical assessment. These features typically include :
- Protrusion of the eyeball (exopthalmos)
- Redness of the eye
- Excessive tearing
- Swelling of the eyelids
- Light sensitivity
Patients with Graves’ opthamology are said to have a startled look and complain of the sensation of having “sand” in the eyes. The widening of the space between the eyelids due to swelling and protrusion of the eyeball does not allow for the eye to be fully shielded during blinking and sleeping. As a result the tip of the eyeball is dry despite the excessive tearing seen with Graves’ opthamology.
Picture of Exopthalmos (protruding eyeball) from Wikimedia Commons