Toxic Multinodular Goiter: When Multiple Thyroid Nodules Cause Hyperthyroidism

What happens in toxic multinodular goiter

Over many years, the thyroid can develop multiple nodules, forming a multinodular goiter. Some nodules acquire mutations, often in the TSH receptor gene, that make them produce hormone independently of TSH, the pituitary hormone that normally controls the thyroid. When enough autonomous tissue accumulates, thyroid hormone levels rise and TSH falls. Hyperthyroidism usually develops gradually, starting as subclinical (low TSH with normal T4 and T3).

A single overactive nodule is called a toxic adenoma.

Causes and risk factors

• long-standing nontoxic multinodular goiter
• iodine deficiency, past or present
• older age, typically over 50
• female sex
• iodine exposure can trigger overt hyperthyroidism in a goiter with autonomous nodules, for example after iodinated CT contrast, amiodarone or iodine supplements (the Jod-Basedow phenomenon)

Symptoms

Hyperthyroid symptoms

• heart palpitations and a fast heart rate
• weight loss despite normal or increased appetite
• heat intolerance and sweating
• tremor
• anxiety, irritability and poor sleep
• frequent bowel movements
• muscle weakness and fatigue

Older adults may have few classic symptoms and present with atrial fibrillation, heart failure, weight loss or depression.

Goiter symptoms

• a visible lump or swelling in the front of the neck
• difficulty swallowing or a feeling of pressure, especially lying down
• breathlessness or noisy breathing if the goiter compresses the windpipe or extends behind the breastbone
• hoarseness, rarely

Unlike Graves' disease, TMNG does not cause thyroid eye disease.

Diagnosis

• thyroid blood tests: low or suppressed TSH, with high or normal free T4 and T3. T3 is often disproportionately raised
• TSH receptor antibodies: usually negative, helping to exclude Graves' disease
• radioactive iodine uptake and scan: shows patchy uptake with "hot" nodules and suppressed surrounding tissue
• thyroid ultrasound: maps nodules. "Cold" nodules that are not overactive may need fine-needle aspiration biopsy to rule out cancer
• CT or breathing tests if the goiter is large or extends into the chest

Treatment

Unlike Graves' disease, TMNG does not go into remission, so definitive treatment is usually recommended.

Radioactive iodine (RAI)

A capsule or drink of iodine-131 is taken up by the overactive nodules and destroys them over weeks to months. It is effective and avoids surgery. It may shrink the goiter by 30 to 50%, though large goiters respond less. Some people develop hypothyroidism afterward and need levothyroxine. It is not used in pregnancy or breastfeeding.

Surgery (thyroidectomy)

Removal of most or all of the thyroid is preferred for:

• large goiters causing compression
• goiters extending behind the breastbone
• suspicious nodules
• when rapid cure is needed
• patient preference

Lifelong thyroid hormone replacement is needed after total thyroidectomy. Risks include damage to the voice nerve and parathyroid glands, which are uncommon with experienced surgeons.

Antithyroid medicine

Methimazole controls hormone levels before definitive treatment, or long term in people who cannot have or prefer not to have RAI or surgery. Low-dose long-term methimazole is a reasonable option for some older adults.

Beta-blockers

Propranolol, atenolol or metoprolol relieve palpitations, tremor and anxiety while thyroid levels are brought down.

Complications

• atrial fibrillation and stroke
• heart failure
• osteoporosis and fractures, especially in postmenopausal women
• thyroid storm, rarely
• compression of the windpipe or esophagus by large goiters

Outlook

With radioactive iodine or surgery, most people are cured of hyperthyroidism. Thyroid levels are monitored afterward to detect hypothyroidism, which is easily treated with a daily tablet.

Frequently asked questions

What is toxic multinodular goiter?

It is an enlarged thyroid containing several nodules that make thyroid hormone independently, causing hyperthyroidism. It develops gradually, usually in people over 50, and is more common in women and in areas with low iodine.

What are the symptoms of toxic multinodular goiter?

Symptoms include palpitations, weight loss, heat intolerance, sweating, tremor, anxiety and sometimes a neck swelling or difficulty swallowing. Older adults may have only an irregular heartbeat, weakness or weight loss.

How is toxic multinodular goiter treated?

Radioactive iodine and surgery are the definitive treatments. Antithyroid medicine such as methimazole and beta-blockers control symptoms before treatment or long term in some people. TMNG does not usually go away on its own.

What is the difference between Graves' disease and toxic multinodular goiter?

Graves' disease is an autoimmune condition with antibodies stimulating the whole thyroid, often with eye disease, and can go into remission. TMNG is caused by multiple independent overactive nodules, has no eye disease, and usually needs definitive treatment.

Can iodine make toxic multinodular goiter worse?

Yes. A large iodine load, such as from CT contrast dye, amiodarone or high-dose supplements, can trigger or worsen hyperthyroidism in a nodular goiter. Tell your doctors about your thyroid condition before procedures.