Graves' disease (Morbus Basedow)

Graves' disease is an autoimmune disease of the thyroid gland and is the most common cause of hyperthyroidism. The immune system mistakenly perceives the thyroid gland as foreign and produces TSH receptor antibodies. The antibodies (TRAK for short) bind to the TSH receptor on the thyroid cells and stimulate the thyroid gland so that it subsequently produces more thyroid hormones. The result is chronic hyperthyroidism and symptoms typical of Graves' disease, such as goiter (enlargement of the thyroid gland) and protruding eyeballs (exophthalmos).

The underlying causes of Graves' disease have not yet been precisely clarified. It is assumed to be an interaction of genetic predisposition (familial accumulation), an increased occurrence of the antigens HLA-B8 and HLA-DR3, and exogenous factors such as smoking, large amounts of iodine, previous viral infections, or severe psychological stress. However, a sudden onset of the disease may occur even when the patient is completely well.

The main focus is on the symptoms of hyperthyroidism:

• Enlargement of the thyroid gland (goiter) in 70-90% of patients.
• nervousness
• irritability
• insomnia
• Cardiac arrhythmia
• Weight loss (despite ravenous appetite)
• Sweating
• Increased stool frequency
• Muscle weakness
• Warm, moist skin
• Soft, thin hair
• Cycle disturbances and possibly infertility in further consequence

In addition, typical symptoms of Graves' disease include:

• Inflammatory diseases of the eye socket (endocrine orbitopathy/ophthalmopathy) in approx. 60% of cases.
• "Merseburg Triad" in 50% of cases, consisting of: Goiter, protrusion of the eyeballs (exophthalmos), and rapid heartbeat (tachycardia).
• Rarely: colored swellings or nodules on the legs or feet (pretibial myxedema or acropachy).

Common eye complaints:

• Foreign body or pressure sensation
• Protruding eyeballs (exophthalmos)
• Eye burning
• Swollen or inflamed eyelids
• Infrequent blinking
• Increased lacrimation
• Sensitivity to light
• Blurred vision to more severe vision impairment

1. AnamnesisMedical interview on the history of the disease and questioning about the intake of iodine-containing medications or contact with X-ray contrast medium.
2. Physical examinationTo determine the physical symptoms of Graves' disease or hyperthyroidism
3. Blood tests- TSH: decreased - fT3: almost always increased - fT4: increased in 90% of cases - detection of TRAK (TSH receptor antibodies) and TPO-Ak (thyreoperoxidase antibodies)
4. Imaging techniques- sonography: increased volume and blood flow to the thyroid gland - scintigraphy: increased thyroid production.

Drug therapy

Treatment is usually medicinal with thyrostatic drugs. Thyreostatics inhibit hormone production and release in the thyroid gland. Thiamazole or carbimazole (precursor of thiamazole) is the drug of choice here; propylthiouracil can also be used as an alternative. Beta-blockers such as propanolol are also given for symptomatic treatment of tachycardia. Propanolol also inhibits the enzyme deiodinase and thus the conversion of the thyroid hormone T4 to the metabolically active T3. As with any hyperthyroidism, treatment with thyrostatic agents should continue until euthyroidism (good thyroid function) is achieved. In Graves' disease, thyrostatic therapy normally lasts 1-1.5 years, in individual cases even longer.

About 6 months after diagnosis or start of therapy, the TRAK level in the blood is checked. This has prognostic significance: at levels > 10 IU/l, the probability that the therapy will still be effective or that the disease will subside is reduced. In this case, the thyroid gland is switched off by radioiodine therapy or surgically removed.

After discontinuation of medication, recurrence (recurrence of the disease) occurs in about 50% of cases, but usually thyroid function normalizes in more than half of patients. Smoking increases the risk of recurrence and worsens ocular involvement in Graves' disease.

In case of non-improvement or recurrence of hypothyroidism after 1-1.5 years of thyrostatic therapy, permanent elimination of the thyroid gland by radioiodine therapy or surgical removal is indicated.

Radioiodine therapy

In radioiodine therapy, radioactive iodine is taken orally, which accumulates in the thyroid gland and destroys the hormone-producing cells. The thyroid gland should be treated in advance with thyrostatic drugs, which are discontinued 2-3 days before radioiodine therapy. In addition, a low iodine diet should be followed and iodine-containing drugs or supplements should be avoided. Since the effect radioiodine therapy occurs only after a few weeks, follow-up treatment with thyrostatic drugs may also be necessary. Hypothyroidism may worsen an existing endocrine orbitopathy (inflammatory disease of the orbits) and should be prevented. Therefore, at the beginning of the onset of action of radioiodine therapy, thyrostatic medication can be combined early with levothyroxine (LT4). Short-term and regular monitoring of thyroid parameters after radioiodine administration is therefore essential. Once thyroid function has been permanently abolished, lifelong thyroid hormone(LT4) substitution is necessary.

Surgical therapy

Surgical removal of the thyroid gland is an alternative to radioiodine therapy. Surgery for Graves' disease is indicated primarily in cases of uncontrolled thyroid growth, endocrine orbitopathy, suspected malignant change in the thyroid gland, severe side effects and intolerance of threostatic drugs, or if the patient refuses radioiodine therapy. Prior to surgery, good thyroid function should always be achieved by thyrostatic pretreatment. In Graves' disease, the entire thyroid gland is usually removed except for a remnant of 2 ml (so-called fast-total thyroidectomy). During surgery, there is a risk of injury to the vocal cord nerve, which can lead to paralysis of the vocal cords and subsequently to temporary to lifelong hoarseness. Thyroid surgery may also cause short-term damage to the parathyroid glands, which are responsible for maintaining blood calcium levels. In this case, calcium must be taken for a few days after surgery, and if the parathyroid glands are permanently damaged, patients must rely on lifelong calcium intake in combination with vitamin D. Even after thyroid removal, thyroid hormone tablets(LT4) must be taken for life and thyroid parameters must be monitored at regular intervals.

Treatment of eye symptoms

For the treatment of the typical eye symptoms, there are the following options, depending on the auprimation:

• Tablets or infusions with cortisone.
• Selenium substitution in mild cases
• Eye drops, ointments and gels for dry eyes
• Irradiation of the eye socket (in severe cases)
• Surgery (to enlarge the eye socket, in severe cases)

Regular monitoring of thyroid parameters or adjustment of the hormone dose as part of care by a thyroid specialist is necessary in any case. The prognosis is good in many cases: after 1-1.5 years, the hyperthyroidism balances out in more than half of the patients. If thyroid function is not (sufficiently) improved despite medication, or if hyperthyroidism recurs, the thyroid gland must be permanently removed or eliminated.

Failure to treat Graves' disease increases the risk of typical late complications of hyperthyroidism, such as cardiovascular disease or bone fractures caused by osteoporosis. Rarely, a life-threatening thyrotoxic crisis (thyrotoxicosis) can also occur. Typical symptoms are high fever, vomiting, restlessness, anxiety and impaired consciousness. In order to avoid cardiac arrhythmias, coma and circulatory failure, affected persons must be treated immediately (possibly with intensive care).

Due to the insufficiently clarified causes for the development of Graves' disease, the disease cannot be directly prevented. The only way to reduce the risk of developing the disease is to avoid smoking or stress.