Written by: Khalil Al-Salem M.D FRCS, FICO
Thyroid eye disease (Graves disease) is an autoimmune disease that leads to a generalized overactivity of the entire thyroid gland. Eye manifestation associated with thyroid eye disease includes; eye bulging , eye redness, swelling of the conjunctiva, double vision, and blurring of vision due to optic nerve compression on rare occasions. The condition is commoner in smokers and women (7-8 times more). Herein, we will be giving patients a good briefing about thyroid eye disease and the new drugs involved in the treatment like Tepezza.

What is the thyroid gland?
The thyroid gland is a butterfly-shaped endocrine gland that is located in the lower front of the neck. The thyroid makes thyroid hormones secreted into the blood and then carried to every tissue in the body. Thyroid hormones help the body use energy, stay warm, and keep the brain, heart, muscles, and other organs working appropriately.
What Causes thyroid hyper activity?
Graves’ disease is triggered by a process in the body’s immune system, which normally protects us from foreign invaders such as bacteria and viruses. The immune system destroys foreign invaders with substances called antibodies produced by blood cells known as lymphocytes. Sometimes the immune system can be tricked into making antibodies that cross-react with proteins on our own cells. In many cases, these antibodies can cause the destruction of those cells. In Graves’ disease, these antibodies (called the thyrotropin receptor antibodies (TRAb) or thyroid-stimulating immunoglobulins (TSI) do the opposite – they cause the cells to work overtime. The antibodies in Graves’ disease bind to receptors on thyroid cells’ surface and stimulate those cells to overproduce and release thyroid hormones.
What are the signs and symptoms of thyroid over activity?

Hyperthyroidism
Which manifest by racing heartbeat, hand tremors, trouble sleeping, weight loss, muscle weakness, neuropsychiatric symptoms and heat intolerance. In other words, the patient is a fighting mood!
Eye disease
Graves’ disease is the only kind of hyperthyroidism that can be associated with inflammation of the eyes, swelling of the tissues around the eyes, and bulging of the eyes. Overall, a third of patients with Graves’ disease develop some signs and symptoms of Graves’ eye disease, but only 5% have moderate-to-severe inflammation of the eye tissues to cause serious or permanent vision trouble. Patients who have any suggestion of eye symptoms should seek an evaluation with an eye doctor (an ophthalmologist) as well as their endocrinologist.
Eye symptoms most often begin about six months before or after Graves’ disease diagnosis has been made. Seldom do eye problems occur long after the disease has been treated. In some patients with eye symptoms, hyperthyroidism never develops and, rarely, patients may be hypothyroid. The severity of the eye symptoms is not related to the severity of the hyperthyroidism.
Early signs of trouble might be red or inflamed eyes, a bulging of the eyes due to inflammation of the tissues behind the eyeball, or double vision. Diminished vision or double vision are rare problems that usually occur later, if at all. We do not know why, but problems with the eyes occur much more often and are more severe in people with Graves’ disease who smoke cigarettes.
Skin disease
Rarely, patients with Graves’ disease develop a lumpy reddish thickening of the skin in front of the shins known as pretibial myxedema (called Graves’ dermopathy). This skin condition is usually painless and relatively mild, but it can be painful for some. Like the eye trouble of Graves’ disease, the skin problem does not necessarily begin precisely when the hyperthyroidism starts. Its severity is not related to the level of thyroid hormone.
How to diagnose thyroid eye disease?
The diagnosis of hyperthyroidism is made based on your symptoms and findings during a physical exam. It is confirmed by laboratory tests that measure the number of thyroid hormones ( T4 and free thyroxine T3) and thyroid-stimulating hormone (TSH) in your blood.
The choice of initial diagnostic testing depends on cost, availability, and local expertise. Measurement of antibodies, such as TRAb or TSI, is cost-effective and, if positive, confirms Graves’ disease’s diagnosis without further testing. If this test is negative, your doctor should refer you to a radioactive iodine uptake test (RAIU) to confirm diagnosis.
Also, in some patients, measurement of thyroidal blood flow with ultrasonography may help establish the diagnosis if the above tests are not readily available.
Treatment of Thyroid eye disease (Graves)?
All hyperthyroid patients should be initially treated with beta-blockers. Treatment options to control Graves’ disease hyperthyroidism include antithyroid drugs (generally methimazole [Tapazole]. Rarely, radioactive iodine and surgery.
Antithyroid medications are typically preferred in patients with a high likelihood of remission (women, mild disease, small goiters, the negative or low titer of antibodies). These medications do not cure Graves’ hyperthyroidism but effectively control hyperthyroidism
If your Graves’ disease persists after six months, your doctor may recommend definitive treatment with either radioactive iodine or surgery.
If surgery (thyroidectomy) is selected as the treatment modality. The surgery should be performed by a skilled surgeon with expertise in thyroid surgery to reduce the risk of complications.
Your doctor should discuss each treatment options with you, benefits and potential side effects, expected recovery speed, and costs. Although each treatment has its advantages and disadvantages, most patients will find one treatment plan that is right for them. Hyperthyroidism due to Graves’ disease is, in general, controllable and safely treated, and treatment is almost always successful.
Tepezza a new Drug in the treatment of thyroid eye disease?
Tepezza is a new Monoclonal antibody used to shrink the muscle and fat in patients ‘ orbit with graves disease. It acts against the IGF1 receptor on the orbital tissue, which is susceptible to thyroid-stimulating hormone.
Who is advised to use Tepezza?
Tepezza is an excellent medication for newly diagnosed thyroid eye disease. Patients with early eye-bulging due to thyroid eye disease gain an enormous benefit from the first couple of doses. It can reverse the eye-bulging by shrinking the size of the expanding eye muscles and fat.
What is the effect of Tepezza on orbital decompression?
Most experts in the field noticed better orbital decompression results when using Tepezza; there is no substantial evidence. However, talking to some experts in the area at the latest American academy meeting confirmed that Tepezza helped many patients achieve better results due to the muscle and fat shrinkage effect.
What are the side effects of Tepezza?
Muscle cramps, falling of hair, hearing problems; some patients complain that their ears are plugged, or they feel they are under water, or they hear their voices louder than normal.
Tinnitus and dizziness also have been documented by treatment. The sensory hearing loss is usually reversible once the medication is stopped
Are patients reluctant to talk about their side effect?
The answer is yes, most patients try to hide side effect of the drug from doctor, fearing they will stop the medication. because they can notice the change Tepezza is doing.
A Base line audio-gram is recommended before starting treatment if Tepezza.
What is the most important beneficial effect documented by patients?
Most patients documented an improvement in their double vision. Which is a game changer for patients not candidates for squint surgery (eye deviation surgery).
Is Tepezza covered by insurance in the states?
Tepezza is a very expensive drug. For this reason, companies are reluctant to cover the medication. However, in the future we think more and more companies will cover the medication.