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The thyroid gland is a small gland, but it plays a crucial role in regulating metabolism and energy production in our body. Among the various disorders that can affect the thyroid, the Graves' disease or Basedow's disease is an autoimmune condition that also leads to important ocular symptoms, which we will examine in this article.

The thyroid gland

The thyroid gland is a small, butterfly-shaped gland located at the front of the base of the neck. It controls many important functions of the body through the production of thyroid hormones and is responsible for controlling metabolism.

Functions of the Thyroid

The thyroid gland produces hormones that are secreted into the bloodstream and then transported to every tissue in the body. The main hormones are the thyroxine (T4) and the triiodothyronine (T3), which affect almost every cell in the body. In fact, thyroid hormones regulate numerous body functions, including respiration, heartbeat and body temperature.

In addition, the thyroid gland plays a crucial role in the development of the nervous system and growth. During pregnancy, thyroid hormones are vital for the proper development of the foetus' brain. Their production is regulated by thyroid-stimulating hormone (TSH), produced by the pituitary gland.

A proper balance of thyroid hormones is essential for maintaining optimal body functions. Dysfunctions can lead to conditions such as hyperthyroidism or hypothyroidism, which have a major impact on the body's well-being.

Importance of the thyroid in health

A properly functioning thyroid gland ensures a balanced metabolism, which is essential for maintaining a healthy body weight. Thyroid problems can cause sudden weight gain or loss, fatigue and mood changes.

A healthy thyroid contributes to cardiovascular health by regulating heart rate and blood pressure. Thyroid hormones also affect mental health, with imbalances that can lead to depression or anxiety.

In addition, the thyroid gland is important for reproductive health, influencing fertility and development during pregnancy. Keeping it healthy is crucial to avoid complications during gestation.

What is Graves' disease

The Graves' disease is an autoimmune disease in which the immune system attacks the thyroid gland, causing excessive production of thyroid hormones. This condition causes hyperthyroidism, which speeds up the metabolism and causes physical and mental symptoms.

More specifically, it results in the production of autoantibodies (antibodies directed against the body's own molecules) directed against the TSH hormone receptor, present on thyroid cells. These autoantibodies stimulate uncontrolled production of thyroid hormones, causing a form of hyperthyroidism characterised by significant eye disorders, with swelling, inflammation and protrusion of the eyeball.

Hyperthyroidism can also be caused by other causes, such as thyroid nodules or taking certain medications, but in about 3 out of 4 cases the cause can be traced back to Graves' disease.

Graves' disease generally occurs before the age of 40 and is 7-8 times more frequent in women than in men.

Symptoms of Graves' disease

Graves' disease often presents itself with a triad of symptoms, which is called 'Triad of Merseburg'named after the German town where Basedow described the first cases of the disease:

• presence of goitrewith a diffuse and usually symmetrical increase in volume of the thyroid gland
• tachycardia (accelerated heartbeat)
• exophthalmos (protrusion of the eyeballs outside the orbits)

Given the influence of thyroid hormones on the functioning of many organs, Graves' disease disorders may also include:

• anxiety, irritability and sleep disorders
• slight tremor of the hands or fingers
• heat sensitivity and increased sweating
• weight loss despite normal eating habits
• changes in menstrual cycles
• erectile dysfunction or reduced libido
• frequent bowel movements
• muscle weakness and fatigue
• thickening and reddening of the skin, at the shins or on the front of the feet (Graves' dermopathy)

Graves' ophthalmopathy

One third of Graves' disease patients present with swollen and inflamed tissue around the eyes, which is characteristic of the condition known as Graves' ophthalmopathy or Graves' orbitopathy.

In about 5% of cases the inflammation of the ocular tissues is so significant that it causes major or permanent vision problems.

The severity of eye disorders is not directly related to the severity of hyperthyroidism.

Symptoms associated with Graves' ophthalmopathy may include:

• protrusion of one or both eyes outwards, symmetrical or asymmetrical (exophthalmos)
• feeling of pressure or pain in the eyes
• swelling or retraction of the eyelids
• reddening and burning of the eyes upon waking
• sensitivity to light (photophobia)
• splitting of vision (diplopia)

Cigarette smoking appears to contribute to more severe manifestations of Graves' disease.

Causes of Graves' disease

The causes of Graves' disease are still being studied, but genetic and environmental factors are believed to play a role. Individuals with a family history of autoimmune diseases are more at risk.

Infection with certain viruses and stress can trigger the disease. Hormonal factors, such as the hormone balance during pregnancy, can also influence the development of Graves' disease.

Lifestyle habits, such as smoking, increase the risk of developing the disease. However, there is no single determining cause and the condition is often the result of a combination of factors.

Diagnosis

Recognising the symptoms of Graves' disease and obtaining an accurate diagnosis is crucial for effective treatment. We look at how to identify the signs and the available diagnostic methods.

Recognising Symptoms

The symptoms of Graves' disease can vary, but some common signs include:

• Unexplained weight lossdespite a normal or increased calorie intake.
• Increased heart ratewith palpitations or arrhythmias.
• Nervousness and irritabilitycaused by increased production of thyroid hormones.
• Heat intoleranceexcessive sweating and feeling hot.
• ExophthalmosA condition in which one or both eyes protrude outwards.

These symptoms may worsen gradually and vary in intensity. It is important to consult a doctor if a thyroid problem is suspected, to avoid more serious complications.

Methods of Diagnosis

The diagnosis of Graves' disease is based on several tests. The main ones include:

1. Blood tests: to measure TSH, T3 and T4 levels. Low TSH and high T3 and T4 suggest hyperthyroidism.
2. Thyroid ultrasoundto assess gland activity and confirm the diagnosis.
3. Antibody testingto detect the presence of TSH anti-receptor antibodies, characteristic of Graves' disease.

The combination of these tests helps to confirm the diagnosis and guide the treatment plan. Regular monitoring is essential to manage the disease over time.

Treatment Options

Treatment of Graves' disease aims to reduce thyroid hormone production and manage symptoms. There are several options available, from drugs to alternative therapies.

Drug therapies

Anti-thyroid drugs

Anti-thyroid drugs are one of the main treatment options and include:

• MethimazoleIt reduces the production of thyroid hormones by blocking the action of the thyroid gland.
• Propylthiouracil (PTU)used especially during pregnancy, it inhibits the synthesis of thyroid hormones.

They are the treatment of first choice, especially in young people, and are generally well tolerated, but can sometimes cause side effects such as:

• rash
• joint pain
• fever
• reduction in the number of white blood cells (leucopenia)
• liver damage (liver failure)
• anaemia

The methimazole cannot be used for the treatment of women in the first trimester of pregnancy, so therapy involves taking propylthiouracil followed by methimazole from the fourth month of pregnancy onwards.

Beta-blockers

Beta-blockers are used to relieve symptoms, such as palpitations and tremors, without directly affecting hormone production.

These drugs are generally effective, but may take months to stabilise hormone levels and related disorders. Regular monitoring is essential to adjust the dosage and assess the effectiveness of the treatment.

Other treatment options

In addition to drugs, there are other options, such as:

• Radiotherapy with radioactive iodineThe thyroid gland needs iodine to produce hormones and, therefore, radioactive iodine (iodine131) is administered by mouth, which is then actively, and almost exclusively, taken up by thyroid cells. Radioactive iodine emits beta and gamma radiation that causes thyroid cell death with subsequent inflammatory reaction and decrease of thyroid hormones in the bloodstream. The therapeutic effect is due to beta radiation for 94%. The reduction of thyroid hormones causes thyroid tissue to shrink and various symptoms to gradually decrease, usually over a period of several weeks to several months.
• Thyroid surgeryPartial or total removal of the thyroid gland, recommended when other therapies are ineffective or in the case of carcinoma.
• Complementary therapiessuch as acupuncture and stress management, which can help improve general well-being.

These therapies can be combined to achieve the best results.

Management and Prevention

Managing Graves' disease requires a holistic approach that includes changes in lifestyle and diet. Long-term prevention is equally crucial for maintaining health.

Lifestyle and Diet

Adopting a healthy lifestyle is essential to manage symptoms. Here are some tips:

• Balanced dietrich in nutrients and low in iodine, to avoid further stimulating the thyroid gland.
• Regular physical activityto improve general well-being and reduce stress.
• Avoiding smokingas it can worsen symptoms and increase the risk of ocular complications.

These changes can improve quality of life and help maintain control of the disease.

Long-Term Prevention

Prevention of Graves' disease is complex, but here are some useful strategies:

• Regular monitoring: of hormone levels and thyroid condition.
• Stress reductionthrough relaxation and emotion management techniques.
• Genetic counsellingfor those with a family history of autoimmune diseases, useful for assessing personal risk.

These measures not only help prevent disease, but also support long-term well-being

• Bartalena L, Tanda ML. Current concepts regarding Graves' orbitopathy. J Intern Med. 2022 Nov;292(5):692-716. doi: 10.1111/joim.13524. Epub 2022 Jun 1. PMID: 35604323; PMCID: PMC9796560.
• Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C, Marinò M, Vaidya B, Wiersinga WM; EUGOGO †. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy. Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67. doi: 10.1530/EJE-21-0479. PMID: 34297684.