Toxic Nodular Goitre

Toxic nodular goitre is a condition where one or more growths in your thyroid gland start producing too much thyroid hormone on their own, leading to an overactive thyroid that can affect your heart, bones, and overall wellbeing.

Table of contents

• What Is Toxic Nodular Goitre?
• The Thyroid Gland
• Types of Toxic Nodular Goitre
• What Causes This Condition?
• Signs and Symptoms
• How Is It Diagnosed?
• Treatment Options

Toxic multinodular goiter, Plummer disease, toxic adenoma

• Thyroid gland
• Neck

What Is Toxic Nodular Goitre?

Toxic nodular goitre is a condition where one or more lumps, called nodules (typically harmless growths), develop in your thyroid gland and begin making thyroid hormone without responding to the body’s normal signals to keep hormone levels balanced.^[1] The result is that too much thyroid hormone gets produced and released into your bloodstream, causing hyperthyroidism (a condition where your thyroid is overactive).^[2]

This condition was first described in 1913 by Henry Plummer, an American physician, which is why it is sometimes called Plummer disease.^[3][5] Toxic nodular goitre is the second most common cause of hyperthyroidism in Western countries, after Graves disease.^[3] In elderly people and in areas where people don’t get enough iodine in their diet, toxic nodular goitre becomes the most common cause of an overactive thyroid.^[3]

The Thyroid Gland

The thyroid gland is a butterfly-shaped organ normally located in the lower front of your neck.^[2] Its job is to make thyroid hormones, which are released into your blood and then carried to every tissue in your body. These hormones help your body use energy, stay warm, and keep your brain, heart, muscles, and other organs working as they should.^[2]

Types of Toxic Nodular Goitre

There are two main forms of this condition, depending on how many nodules are involved.^[2]

When there is a single nodule making the extra amount of thyroid hormone, it is called a toxic nodule or toxic adenoma.^[2] In a toxic multinodular goitre, there is more than one nodule producing extra thyroid hormone—usually several nodules are involved.^[2] In this type, there may still be some nodules that are not toxic and not making thyroid hormone.^[2]

Hyperthyroidism mainly occurs when single nodules are larger than 2.5 centimeters across.^[3]

What Causes This Condition?

The development of toxic nodular goitre appears to be related to not getting enough iodine in the diet.^[3] When your body lacks iodine, it leads to low levels of thyroid hormone. This causes thyroid cells to multiply to try to make up for the low hormone levels.^[3]

When thyroid cells multiply more often, individual cells can develop changes in their genetic material called somatic mutations (genetic changes that happen in certain cells but are not passed down through families).^[3] These mutations can occur in the receptor for thyroid-stimulating hormone (TSH), which is the signal from your brain that normally controls how much thyroid hormone gets made.^[3] These mutations are found in 20 to 80 percent of toxic nodules.^[3]

The mutations cause the thyroid cells to become “autonomous,” meaning they function independently and no longer respond to the normal control signals from the brain.^[3] These altered cells then multiply and form nodules that produce thyroid hormone on their own. About 10 percent of autonomously functioning nodules eventually become toxic.^[3]

Several factors can increase your risk of developing this condition. Women are more likely to develop toxic nodular goitre than men—it affects women about four times more often.^[5] The condition is also more common in people over 40 years of age, and most patients are older than 50.^[5][11] Having a family history of thyroid disease or thyroid nodules also increases your risk.^[5] Additionally, if your head and neck have been exposed to radiation for medical treatments, you may be at higher risk.^[5]

Signs and Symptoms

The signs and symptoms of toxic nodular goitre are similar to those of other types of hyperthyroidism.^[3] However, the onset of symptoms is usually more gradual and less dramatic than with other causes of overactive thyroid.^[13] Some patients, especially elderly people, may have very mild signs and symptoms or even none at all—a condition called subclinical hyperthyroidism (where only laboratory tests show TSH suppression but there are no obvious symptoms).^[13]

Most patients initially notice visible swelling in the neck or enlargement of the neck area from the goitre itself.^[6] The size of a goitre can range from very small and barely noticeable to very large.^[14] Most goitres are painless.^[14]

When symptoms of excess thyroid hormone do occur, they may include feeling unusually warm, increased appetite with weight loss, nervousness or feeling anxious, rapid or irregular heartbeat, trembling hands, muscle weakness, and more frequent bowel movements.^[13] Some people may also experience mood changes such as depression.^[13]

If the goitre becomes large enough, it can press on nearby structures in the neck, causing difficulty breathing (especially when lying flat), a sensation of food or pills getting “stuck” in the throat, a choking feeling, or a sense of fullness in the neck.^[6] These symptoms are more common if the goitre is growing downward into the chest, called a substernal goitre.^[6]

How Is It Diagnosed?

The diagnosis of hyperthyroidism is made based on your symptoms, physical examination findings, and confirmed by laboratory blood tests showing excess thyroid hormone.^[2] In hyperthyroidism, there is a high level of thyroid hormone in the blood plus a low level of TSH.^[2]

Once hyperthyroidism is confirmed, your doctor may order a thyroid scan to determine the cause.^[2][11] This test uses a small amount of radioactive iodine to show where the thyroid is functioning and how active different areas are. A toxic nodule appears as a single area of overactivity on the scan, while a toxic multinodular goitre shows multiple overactive areas, creating a patchy appearance.^[2][3]

A thyroid ultrasound can also be used to better evaluate the presence and characteristics of thyroid nodules.^[2][6] Ultrasound uses sound waves to create images and does not involve radiation.^[6] It allows the doctor to see the size of the thyroid and specific features of the nodules, including their number, whether they contain calcium deposits, their borders and shape, and whether they are solid or filled with fluid.^[6]

In some cases, your doctor may recommend a fine-needle aspiration biopsy to make sure there is no cancer.^[6] During this procedure, a very thin needle is placed into the nodule and a sample of cells is removed and examined under a microscope.^[6]

Treatment Options

Unlike some other thyroid conditions, toxic nodular goitre is not an autoimmune disease and rarely, if ever, goes away on its own.^[7] Therefore, patients who have autonomously functioning nodules should be treated with definitive therapy—either radioactive iodine or surgery.^[7]

Patients with subclinical hyperthyroidism should be monitored closely. Some doctors suggest that elderly patients, women with bone loss, and patients with risk factors for heart rhythm problems should be treated even when they have only mild disease.^[7]

Medications

Medications called antithyroid drugs can be prescribed to control thyroid hormone production and reduce symptoms.^[11] Beta-blockers can also help reduce symptoms related to excess thyroid hormone, such as rapid heartbeat.^[3]

However, these drugs only temporarily control hormone production and prevent complications. If the medication is stopped, the hyperthyroidism comes back.^[11] Therefore, these medications are more of a bridge to definitive treatment rather than a final solution.^[11] They can also help control hormone production in preparation for definitive treatments such as surgery or radioactive iodine therapy.^[11]

Radioactive Iodine Therapy

In the United States and Europe, radioactive iodine is considered the treatment of choice for toxic nodular goitre.^[7] The only absolute reason not to use it is pregnancy.^[7] This treatment is safe and effective when used alone or in combination with other approaches.^[2]

A single dose of radioiodine therapy has a success rate of 85 to 100 percent in patients with toxic nodular goitre.^[7] Radioiodine therapy may also reduce the size of the goitre by up to 40 percent.^[7]

Patients with toxic nodular goitre tend to have less iodine uptake than patients with other causes of hyperthyroidism, so they generally need higher doses of radioactive iodine.^[7] In patients with very low uptake, pretreatment with certain medications can increase the effectiveness of the radioiodine treatment.^[7]

After radioiodine treatment, hypothyroidism (underactive thyroid) develops in 10 to 20 percent of patients, which is similar to the rate after surgery.^[7] Between 3 and 10 years after treatment, the yearly incidence of developing hypothyroidism is about 1.5 percent.^[7] Compression of the windpipe due to thyroid swelling after radiation therapy is no longer thought to be a significant risk.^[7]

Surgery

Surgery may be recommended for patients with very large goitres, especially those causing compression symptoms, or when there is concern about cancer.^[6] Surgery is also an option when radioactive iodine therapy is not suitable or preferred by the patient.^[7]

The surgical approach depends on whether there is a single toxic nodule or multiple nodules. After surgery, hypothyroidism can occur in 10 to 20 percent of patients, similar to the rate after radioiodine therapy.^[7]