Clinical studies on patients with hyperthyroidism in Bulgaria

Our team of investigators has been involved in multiple clinical studies involving patients with hyperthyroidism. Due to our endocrinology team’s exceptional patient access for individuals with this condition, we are the primary point of contact and site for conducting such studies in Bulgaria. Here are some of the studies we have participated in:

  1. A single-center phase 2 study to assess the safety and effectiveness of XXXXXX (specific drug/therapy) in patients with severe thyroid eye disease;
  2. Clinical trials designed to evaluate the safety, effectiveness, and tolerability of XXX therapy in both healthy subjects and patients with hyperthyroidism.

 What is hyperthyroidism?

 Hyperthyroidism, or thyrotoxicosis, is a condition resulting from an overactive thyroid gland. The thyroid gland secretes hormones called thyroxine (T4) and triiodothyronine (T3), levels of which are inversely dependent on the thyroid-stimulating hormone (TSH) released by the pituitary gland. When T3 and T4 are released into the bloodstream in unnaturally high amounts, symptoms characteristic of various different conditions arise. This is because thyroid hormones affect metabolism, growth, development, and numerous other processes in the human body.

How does thyrotoxicosis manifest? The most typical symptoms of hyperthyroidism include:

  • Rapid heartbeat (usually above 100 beats per minute)
  • Irregular pulse
  • Hypertension (high blood pressure)
  • Irritability
  • Restlessness
  • Sleep disturbances
  • Weight loss despite increased appetite
  • Excessive sweating
  • Heat intolerance
  • Fatigue
  • Muscle weakness
  • Menstrual irregularities
  • Thinning of the skin
  • Nail abnormalities
  • Increased bowel movement, sometimes leading to diarrhea

Affected individuals may have a characteristic expression on their faces, displaying surprise and fear, particularly in their eyes. Additionally, individuals with Graves’ disease (another name for hyperthyroidism) may experience swelling of the muscles and tissues behind the eyeballs. This condition is also known as Graves’ disease, autoimmune thyroiditis, and immune hyperthyroidism.

With this condition, the upper eyelids lift, causing the eyes to appear enlarged and bulging. Affected individuals become overly sensitive to light, complain of dryness, and experience redness of the conjunctiva, as well as other forms of visual discomfort.

Thyrotoxicosis is a condition characterized by an increased production of hormones from the thyroid gland. The thyroid gland is an endocrine organ that produces hormones called triiodothyronine and thyroxine, and it has a butterfly-shaped structure located in the neck area, in the front. It is the largest endocrine gland in the human body, weighing around 20-25 grams.

The thyroid hormones play a crucial role in regulating the body’s metabolism. When there is an excess production of thyroid hormones, the metabolism is heightened. This can lead to weight loss, tremors, fatigue, increased sweating, hot flashes, insomnia, and anxiety. In Graves’ disease, the cause of hyperthyroidism is an autoimmune process that occurs in the thyroid gland and results in an increased hormonal production of thyroid hormones.

In some cases of thyrotoxicosis, the elevated production of thyroid hormones can be due to a single or multiple nodules in the thyroid gland (toxic adenoma or toxic multinodular goiter). Other causes of thyrotoxicosis can include inflammation of the thyroid gland, the use of certain medications (such as amiodarone), or taking high doses of levothyroxine.

Thyrotoxicosis is relatively common and occurs more frequently in women. It can manifest with various symptoms, including eye discomfort and conjunctival redness, along with the other typical symptoms associated with hyperthyroidism. Proper diagnosis and management are essential to address the underlying cause and alleviate the symptoms.

Treatment options may include medications to control thyroid hormone levels, radioactive iodine therapy, or, in some cases, surgical removal of the thyroid gland. Regular monitoring and follow-up with a healthcare provider are crucial for individuals with thyrotoxicosis.

What is hyperthyroidism

What to expect of hyperthyroidism:

Symptoms of mild hyperthyroidism can go unnoticed for a long time as they are nonspecific, and in some individuals, hyperthyroidism may be asymptomatic. Early symptoms of hyperthyroidism can be mild, but the condition and symptoms can worsen over time if left untreated. Early symptoms include heat intolerance, increased bowel movements, restlessness, weight loss, and irregular menstruation in females.

Older individuals may experience more frequent irregular heart rhythm and shortness of breath compared to younger individuals. If hyperthyroidism is left untreated, the condition can significantly worsen and lead to a condition known as thyroid storm or thyroid crisis, which is an extremely severe and life-threatening state characterized by fever, rapid heartbeat, high blood pressure, disorientation, nausea, and vomiting.

If you experience any symptoms characteristic of thyroid storm, you should seek immediate medical attention. Treatment for hyperthyroidism should be directed at addressing the underlying cause and aiming to normalize thyroid hormone levels within their reference ranges.

What triggers the activity of the thyroid gland?

Increased synthesis of thyroid hormones usually occurs under the following conditions:

  1. Graves’ disease: This is the most common cause of hyperthyroidism. It affects nearly 80 percent of people with clinically and laboratory confirmed thyrotoxicosis. It is an autoimmune disease where the amount of thyroid-stimulating hormone (TSH) in the blood decreases, leading to an excessive production of T3 and T4.
  2. Toxic nodules: Hyperthyroidism can occur due to the presence of one or more nodules in the thyroid gland that autonomously and independently secrete T3 and T4. This results in an excess of thyroid hormones in the blood, leading to the aforementioned discomforts.
  3. Thyroiditis: This refers to inflammation of the thyroid gland. During the course of this process, thyroid hormones increase, and those affected may experience symptoms typical of hyperthyroidism.
  4. Medication-induced thyrotoxicosis: This condition arises after thyroid hormone therapy when the dosage exceeds the prescribed limit. Similarly, other medications that stimulate thyroid activity can have a similar effect. It has long been known that excessive iodine intake can also lead to hyperthyroidism.
  5. Benign thyroid tumors: By acquiring secretory function, these tumors contribute to an overproduction of hormones.
  6. Genetic predisposition: Graves’ disease is most commonly inherited, and it primarily affects women.
  7. Thyroid storm: This is a rare and life-threatening condition that occurs when the thyroid gland suddenly starts producing large amounts of hormones. It is usually triggered by severe stress, surgical intervention, or infection. Improperly dosed antithyroid drugs can also cause a thyroid storm.
What triggers the activity of the thyroid gland

How is hyperthyroidism diagnosed?

Often, the affected individual may notice an increased heart rate and an enlargement of the thyroid gland, visible as a swelling in the front of the neck. Sometimes, bulging of the eyes and trembling hands can also be present.

In such cases, laboratory tests are performed to confirm whether there is a deviation in the function of the thyroid gland. Blood levels of thyroid hormones (T3 and T4) and thyroid-stimulating hormone (TSH) are mandatory to be evaluated.

If T3 and T4 levels are elevated, and TSH level is low, it indicates hyperthyroidism. In cases of autoimmune disorders, the levels of anti-thyroid antibodies are also assessed.

In the past, X-ray imaging was widely used as a diagnostic tool, but now ultrasound examination of the thyroid gland, known as thyroid ultrasonography or echography, is preferred. It is informative, painless, safe, and does not expose the patient to any radiation.

If structural problems in the thyroid gland are detected, further investigations such as nuclear magnetic resonance (MRI) or computerized tomography (CT) are performed due to their high-resolution capabilities in diagnosing thyroid conditions.

How is hyperthyroidism diagnosed

When there is suspicion of a malignant process, a fine-needle aspiration biopsy is conducted, and if it is necessary to monitor the functional activity of the thyroid gland, a radioisotope study is carried out.

Treatment for hyperthyroidism is tailored based on the patient’s age, overall health, the cause, and severity of hyperthyroidism. The following approaches are commonly used:

  1. Antithyroid medications: These drugs reduce or halt the production of thyroid hormones without causing permanent changes to the thyroid gland. The treatment is usually long-term, and after stopping the medication, the likelihood of recurrence is high. About 5% of patients using antithyroid tablets may experience allergic reactions. Additionally, a decrease in white blood cells, making the patient susceptible to infections, can be observed as a side effect. Other side effects may include liver damage, abdominal pain, and frequent fatigue. Regular monitoring of thyroid function is necessary during treatment, and adjustments may be made as needed.
  2. Beta-blockers: These medications are often prescribed to normalize high blood pressure. While they do not lower thyroid hormone levels, they can help control certain symptoms of thyrotoxicosis, such as tremors, rapid pulse, and palpitations.
  3. Other medications: In cases of thyroid storm, treatment is primarily symptomatic. Corticosteroids, sedatives, medications to lower body temperature, and intravenous fluids may be administered.
  4. Radioactive iodine: This treatment is based on the fact that overactive thyroid cells absorb radioactive iodine, which damages them. It does not affect other parts of the body. Through one or several doses, the thyroid gland shrinks, and T4 and T3 levels in the blood decrease. However, this results in permanent destruction of the thyroid gland, requiring lifelong thyroid hormone replacement therapy.
  5. Thyroidectomy: This refers to the surgical removal of either the entire thyroid gland or part of it. The surgical procedure eliminates hyperthyroidism but typically leads to hypothyroidism. Patients undergoing this method need to be on replacement therapy for the rest of their lives to maintain appropriate thyroid hormone levels. There is a risk of damaging the parathyroid glands that regulate calcium levels in the blood and affecting the nerve that stimulates the vocal cords. This operation is suitable for patients with large tumors causing compression on nerves, blood vessels, and vocal cords, as well as those with malignant thyroid diseases.

Timely treatment of hyperthyroidism is crucial to avoid potential complications, including metabolic disorders, cardiovascular issues, and bone problems. Ensuring adequate intake of essential nutrients, especially proteins, vitamins, and minerals, is also important to compensate for the increased metabolic rate. Strengthening the immune system should be a primary concern as well.

Hyperthyroidism is a pathological condition characterized by an excessive production of thyroid hormones – T3 and T4. It most commonly occurs due to autoimmune disorders (Graves’ disease), toxic multinodular goiter, toxic adenoma, subacute thyroiditis, increased iodine intake, and others.

Elevated levels of thyroid hormones in the blood accelerate metabolic processes and affect the function of many organs and systems, including muscles, cardiovascular system, gastrointestinal tract, eyes, reproductive system, and nervous system.

Neurological symptoms in hyperthyroidism are particularly characteristic and are associated with increased activity of the sympathetic nervous system, hormonal imbalances, and autoimmune mechanisms. These neurological symptoms can manifest from both the central nervous system and peripheral nerves.

Treatment for hyperthyroidism

The most common neurological symptoms in hyperthyroidism include:

  1. Neuropsychiatric symptoms: These are some of the earliest manifestations of hyperthyroidism. Patients may experience increased irritability, restlessness, emotional lability, insomnia, decreased ability to concentrate, and even psychosis with auditory and visual hallucinations.
  2. Motor disturbances: Patients with hyperthyroidism often exhibit psychomotor agitation. They may have rapid and lively speech, rapid changes in facial expressions (hypermythia), and exaggerated deep tendon reflexes. Fine tremors in the hands are commonly observed and may also affect the whole body. Other motor disturbances may include chorea (involuntary, brief, and purposeless movements), choreoathetosis, and ballism.
  3. Thyrotoxic encephalopathy (also known as “thyroid storm”): This is a rare condition that can occur in untreated patients with hyperthyroidism. It may be caused by the direct effect of elevated thyroid hormones or may be associated with increased levels of antibodies against the thyroid-stimulating hormone receptor (TRAb). Clinical manifestations of thyrotoxic encephalopathy include cognitive impairments, memory loss, confusion, hallucinations, generalized or focal tonic-clonic seizures, myoclonus, and others. Seizures and symptoms of thyrotoxic encephalopathy resolve, and the electroencephalogram (EEG) normalizes after treatment of the hyperfunction of the thyroid gland with antithyroid medications (thyrostatics). In cases where encephalopathy is associated with high titers of autoantibodies, treatment with corticosteroids is effective.
  4. Exophthalmic ophthalmoplegia (infiltrative ophthalmopathy) Exophthalmic ophthalmoplegia is characterized by weakness of the extraocular muscles and exophthalmos (protrusion of the eyeballs). There are limited movements of the eyeball, mainly upward (vertical gaze palsy) and to the sides. Patients may experience eye pain, diplopia (double vision), lagophthalmos (incomplete eyelid closure), rare blinking, corneal exposure, and other related symptoms.
  5. Muscular weakness: Approximately 50% of patients may have chronic thyrotoxic myopathy, which is a neuromuscular disorder caused by the increased production of thyroid hormones.
  6. Thyrotoxic myopathy presents with progressive muscle weakness, predominantly affecting the striated muscles. Muscles of the shoulder girdle and thigh muscles are primarily affected. Patients may experience general weakness and easy fatigue with physical exertion. Difficulty in climbing stairs, getting up from a chair, and raising arms above the head may be observed. Severe cases may lead to muscle atrophy.
  7. Thyrotoxic periodic paralysis: Thyrotoxic periodic paralysis manifests as recurrent episodes of mild to severe muscle weakness and low blood potassium levels. Thyrotoxic neuropathy (Graves’ paraplegia): Polyneuropathy (damage to multiple peripheral nerves) is a rare but possible manifestation of severe hyperthyroidism. It primarily affects the nerves supplying the muscles of the lower extremities (Graves’ paraplegia). It presents with pronounced muscle weakness in the lower limbs, absent deep tendon reflexes, and sensory disturbances.

These neurological manifestations can significantly impact the quality of life of patients with hyperthyroidism and require appropriate management and treatment. Early recognition and intervention are essential to prevent complications and improve outcomes.