Graves’ disease is the most common cause of hyperthyroidism and thyrotoxicosis due to increased thyroid hormones and damage to tissues. Although it can be seen at any age, it is most common between the ages of 20-50. It is 5 times more common in women than men.
Graves’ disease is a disease with systemic manifestations affecting the heart, skeletal muscles, eyes, skin, bone and liver. There is usually a combination of thyrotoxicosis, goiter and ophthalmopathy. Graves’ disease can trigger thyroid storm if not diagnosed early. In advanced stages, it can cause serious cardiac complications such as atrial flutter, atrial fibrillation and high-output heart failure.
Graves’ disease is an autoimmune disease of unknown cause. Familial predisposition is quite common. Along with genetic factors, environmental factors are also effective. Stress, smoking, infections and iodine use are thought to increase susceptibility to the disease.
It is also thought that increased immune activity after birth in women with genetic predisposition triggers Graves’ disease.
In Graves’ disease, T lymphocytes become sensitive to antigens in the thyroid gland and stimulate B lymphocytes, causing B lymphocytes to secrete thyroid stimulating antibodies. These antibodies stimulate TSH receptors on the walls of thyroid cells and increase thyroid hormone secretion, similar to TSH secretion. In these patients, thyroid stimulating antibodies are detected in the blood.
As a result of overstimulation of thyroid cells in Graves’ disease, both hyperthyroidism develops and enlargement of the thyroid gland occurs.
Inflammation and cellular proliferation caused by the effect of thyroid-stimulating hormones in Graves’ disease cause the growth of muscles and retro-orbital connective and adipose tissues around the eyes. This condition is called Graves’ ophthalmopathy. Proptosis, pain, diplopia, redness, congestion and periorbital edema occur in the eye.
Pretibial edema may also develop in Graves’ disease. Many symptoms such as tachycardia, sweating, tremor, eyelid lag, vivid and staring gaze, which are the symptoms of hyperthyroidism, can be seen together.
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Diagnosis of Graves’ disease:
Patients with Gravse’s disease often apply to a physician with symptoms of hyperthyroidism. Complaints such as irritability, easy fatigue, diarrhea, excessive sweating, heat intolerance, and hyperkinesia can be expressed. In these patients, enlargement of the thyroid gland, ocular findings due to thyrotoxicosis, and muscle weakness can be seen. Moisture can be seen in the hands due to hyperthyroidism. Since the blood flow in the thyroid gland is accelerated, even a murmur can be detected by listening.
Bone development can be accelerated in pediatric patients. In elderly patients, cardiovascular symptoms predominate.
In Graves’ patients, the thickened and orange skin is more prominent, especially on the anterior surface of the tibia bone. This condition is called Graves’ dermopathy.
Bone lump can also be seen in Graves’ disease. Swelling can be seen in the bones and especially in the hand bones.
Thyroid hormone profile is examined in all patients with suspected thyroid disease. T3, T4 and TSH values are investigated. T3 and T4 levels are high in patients. It is observed that TSH levels are suppressed by external administration of T3 and T4.
In Graves’ patients, thyroid stimulating immunoglobulin, thyrotropin-binding inhibitory (TBI) immunoglobulin, or thyrotropin-binding inhibitory immunoglobulin (TBII) values are examined.
Detection of TSH receptor antibodies is 97% sufficient for diagnosis. Thyroid receptor antibodies are tested in pregnant women, in patients who cannot undergo radioactive iodine uptake testing, in patients with Graves’ ophthalmopathy/orbitopathy without hyperthyroidism, in patients using amiadaron, in patients currently or recently treated with iodine, and in patients currently receiving treatment for hyperthyroidism. In addition, TSH receptor antibodies can be examined to determine the condition and risks of the baby in pregnant patients known to have Graves’ disease.
Radioactive iodine uptake is high in Graves’ patients. An increase in blood flow is detected in the thyroid gland examination with Dopperl ultrasonography.
CT or MR imaging can be performed only in patients with ocular symptoms.
Treatment of Graves’ disease:
The aim of Graves’ disease is rapid symptom control and balancing of thyroid hormones.
Beta blockers are used to regulate heart rate, especially in elderly patients with tachycardia symptoms. 25 or 50 mg of atenolol can be used once a day. The conversion of propranolol from T4 to T3 can also be utilized due to its suppressive effect. Calcium channel blockers such as diltiazem and verapamil can also be added to the treatment if needed.
To reduce thyroid hormone secretion in Graves’ disease:
- Antithyroid drugs (thionamides) may be used
- Radioactive iodine therapy can be applied
- Total or subtotal thyroidectomy can be performed.
Antithyroid drugs methimazole, carbimazole and propylthiouracil reduce the production of thyroid hormone by suppressing the activity of thyroglobulin by thyroid peroxidase.
It is preferred in non-pregnant patients because of its less hepatotoxic side effects. Propylthiouracil is used if necessary, especially in the first trimester of pregnancy.
Before starting antithyroid drug therapy, the patient’s necessary laboratory tests and liver functions are evaluated. Antithyroid drug therapy is not started in neutropenic patients. The patient is informed about the possible effects.
Antithyroid drug therapy is closely followed until thyroid functions return to normal. If thyroid functions return to normal, 6-month controls are performed with maintenance dose treatment.
In Graves’ disease, antithyroid drug therapy is usually applied for 12-24 months. If the thyroid dimensions return to normal, the disease can be controlled with low-dose therapy, and the thyroid stimulating antibodies are no longer detectable, the patient is in remission.
Radioactive iodine treatment in Graves’ disease requires one of the following conditions:
- patient over 21 years old
- non-pregnant adult patient
- The patient who does not plan pregnancy within 6-12 months after treatment
- Patient at risk for surgery
- Patient with contraindicated antithyroid (thionamide) drug therapy
Radioactive iodine therapy is contraindicated in the following situations:
- Pregnancy
- breastfeeding period
- Concomitant thyroid cancer
- Moderate or severe Graves’ ophthalmopathy
- People who cannot comply with radiation safety
Radioactive iodine therapy is administered with a single dose of medication. The treatment dose is calculated with precision. In patients with very high thyroid hormone levels and high risk of complications, radioactive iodine treatment, a pretreatment preparation period with beta blockers and methimazole are applied. No methimazole is used during this preparation period. If the patient is using methimazole, it is stopped 3-5 days before. In patients who will be treated with radioactive iodine, pregnancy should be questioned first.
After radioactive iodine treatment, the patient is followed up with thyroid function tests. If hyperthyroidism recurs after 6 months of follow-up, radioactive iodine treatment is considered unsuccessful. Treatment may need to be repeated.
Surgical treatment in Graves’ disease can be applied in the following cases:
- In patients with thyroid gland size over 80 g
- In patients with multinodular goiter greater than 4 cm
- In patients with neck pressure symptoms
- In patients who are allergic to or unresponsive to antithyroid therapy
- In patients not compliant with antithyroid therapy
- In patients who do not accept radioactive iodine treatment
- In patients with suspected concomitant thyroid cancer
- In patients with cold nodules
- In patients with accompanying parathyroid adenoma
- Patients with high titoid stimulating antibody (TSAb) levels
- In patients with moderate or severe Graves’ ophthalmopathy
Before surgical treatment, antithyroid treatment is given until the patient becomes euthyroid. Preoperative beta-blockers can also be used when necessary. Daily potassium iodide therapy can be given, starting 7-10 days before the surgery. In addition, blood calcium and vitamin D levels are evaluated in patients.
Total thyroidectomy is usually performed in surgical treatment. Complications of surgery can be seen at a rate of 1% after surgery. Antithyroid drugs and beta blockers are discontinued after surgery. Thyroid replacement therapy is started. The thyroid hormone profile is frequently evaluated.
Apart from surgical treatment, treatment is planned according to the severity of orbitopathy in patients who develop Graves’ orbitopathy.