What is hyperthyroidism?

The thyroid is a gland located in the front part of the neck and has a shape similar to a butterfly. It is responsible for producing hormones (T4 and T3) that help regulate the body's metabolism. Excessive production of thyroid hormones (hyperthyroidism) increases metabolism and can lead to various symptoms. A precise diagnosis and appropriate treatment with an endocrinologist are necessary to achieve hormonal control.

Incidence

Approximately 1% to 2% of people will develop hyperthyroidism at some point in their lives. In the United States, around 500,000 new cases are diagnosed each year. As with other thyroid disorders, the incidence is about three to four times more common in women than in men.

Cause

The most common cause is Graves' disease, an autoimmune condition that accounts for over 70% of cases, characterized by increased hormone production throughout the entire thyroid gland. The TRAb antibody binds to the TSH receptor in the thyroid and stimulates it to produce more hormone. Graves' disease is more common in young women and often there is a family history of thyroid disease.

Other forms of hyperthyroidism are related to the development of one or more thyroid nodules that become autonomous—that is, they no longer require TSH stimulation to function. Depending on the number of autonomous cells, they may produce excess thyroid hormone. When caused by a single nodule, the condition is known as Plummer’s disease or toxic uninodular goiter (TUG), accounting for about 5% of cases. When caused by multiple nodules, it is called toxic multinodular goiter (TMNG) and is responsible for about 10% of hyperthyroidism cases. This type of condition is more common in older individuals (over 60 years), has no defined genetic component, and despite being nodular, carries minimal risk of cancer.

In the first trimester of pregnancy, due to elevated levels of the hormone hCG, a transient form of hyperthyroidism may occur that does not require treatment. hCG is a hormone similar to TSH and can bind to its receptors in the thyroid, increasing T3 and T4 production.

Viral or chronic thyroiditis can also cause hyperthyroidism in its early phase.

Excessive doses of levothyroxine, used to treat hypothyroidism, may lead to a condition more accurately described as thyrotoxicosis.

Rarely, a pituitary disorder may cause excessive TSH production, which in turn induces hyperthyroidism. This condition is known as a TSH-secreting pituitary adenoma (TSHoma).

Symptoms

The symptoms of hyperthyroidism tend to be more pronounced depending on the intensity and cause of the condition. In general, the thyroid enlarges (goiter). The patient may lose weight despite eating well and may become more nervous and irritable. There is also a tendency to feel hot and sweat more. The skin, nails, and hair become thinner.

If the condition persists, muscle weakness and tremors in the extremities may occur. Heart rate tends to increase (reaching up to 100 beats per minute), and cardiac arrhythmias may develop. Bowel movements become more frequent, and stools are softer. Women may experience menstrual irregularities, such as amenorrhea (absence of menstruation).

In Graves' disease, in addition to the symptoms already mentioned, eye changes may occur, ranging from upper eyelid retraction to a more complex condition involving swelling of the tissues behind the eyes, leading to eye protrusion (exophthalmos). Other forms of hyperthyroidism may be accompanied by periodic muscle paralysis, often triggered by sugar intake.

Unlike hypothyroidism, there is no direct correlation between the severity of symptoms and the degree of hormonal imbalance. There is a strong dependence on individual susceptibility. Generally, older individuals tend to have more cardiac symptoms, while younger individuals may present more neuropsychological symptoms.

As with hypothyroidism, isolated symptoms do not define hyperthyroidism; multiple symptoms are usually present. Nearly all manifestations of hyperthyroidism are reversible with proper treatment.

Below is a summary of the main symptoms that may indicate hyperthyroidism:

weight loss
tremors in the extremities – especially hands
insomnia
changes in bowel habits – diarrhea
excessive sweating
cardiac arrhythmia (typically in individuals over 50)
palpitations
anxiety – irritability
muscle weakness in the upper and lower limbs
enlargement of the front of the neck – Diffuse goiter (in Graves' disease)
hardened swelling in the front of the leg – Pretibial myxedema (in Graves' disease)
eye disease – bulging eyes (in Graves' disease)

Diagnosis

The suspicion of hyperthyroidism can be confirmed by measuring free T3 and T4 levels (which should be elevated) and TSH (which should be very low). However, to determine the underlying cause of the condition, additional tests may be necessary. In suspected cases of Graves' disease, TRAb antibody testing can confirm the diagnosis. In cases of toxic uninodular goiter (TUG) and toxic multinodular goiter (TMNG), thyroid scintigraphy (radioactive iodine uptake scan) is particularly useful. Ultrasound is also often used to help define the type of thyroid abnormality.

Identifying the etiology of hyperthyroidism is essential for determining the appropriate treatment strategy.

Treatment

There are three main treatment options for hyperthyroidism:

Medical treatment: using antithyroid drugs (ATDs) that block the production of thyroid hormones. These typically take about two weeks to begin working and around ten weeks to control hyperthyroidism. In the case of Graves' disease, remission may be achieved in 30% to 70% of cases (though relapses can occur), requiring treatment for 12 to 24 months. For toxic uninodular goiter (TUG) or toxic multinodular goiter (TMNG), the treatment is only temporary, as remission is not expected. These drugs have notable toxicity, with about 5% of patients developing skin allergies. More seriously, a significant drop in neutrophil levels (a type of white blood cell that defends against bacterial infections) may occur. This severe reaction, called agranulocytosis, affects about 0.3% of ATD users
Surgery: involves removing about 90% of the thyroid gland. Patients are usually stabilized with ATDs before surgery, which should be performed by a specialized surgeon (typically a head and neck surgeon), as there are two critical structures near the thyroid that must be preserved: the recurrent laryngeal nerve, which controls the vocal cords, and the parathyroid glands, which regulate calcium metabolism
Radioactive iodine: uses an isotope of iodine, I-131, administered orally on an outpatient basis, which proportionally destroys thyroid tissue. It has been used routinely since the 1930s with high safety, and over 80% of patients are effectively treated with a single dose. It is the preferred method among American endocrinologists for treating Graves' disease and toxic uni- or multinodular goiter. It is completely contraindicated during pregnancy

More recently, in cases of TUG and TMNG, minimally invasive treatments using radiofrequency, laser, or percutaneous ethanol injection into hormone-producing nodules have proven to be effective alternatives for controlling the condition. Depending on the clinical manifestations of hyperthyroidism, the physician may also prescribe other medications to help control specific symptoms such as nervousness, tremors, or palpitations.

By Einstein Editorial Board