Toxic Multinodular Goiter - Pathogenies and Clinical Management

Introduction:

Toxic multinodular goiter (a condition that causes excess thyroid hormone production due to multiple non-cancerous bumps to develop in the thyroid gland) usually occurs in pre-existing goiters; the condition is prevalent in older adults, and females have a higher risk of developing this condition. Toxic multinodular goiter, also known as Plummer disease, is the second most common cause of hyperthyroidism (excessive production of thyroid hormones) after Graves disease (a disorder of the immune system that leads to excess thyroid hormone production). The symptoms of toxic multinodular goiter are very similar to hyperthyroidism because of the association of hyperthyroidism with the condition. Toxic multinodular goiter may consist of active and inactive nodules. Active autonomous nodules are nodules that are capable of producing thyroid hormones without thyroid-stimulating hormones (a hormone that provokes the thyroid gland to secrete the thyroxine hormone). At the same, inactive thyroid nodules do not produce thyroid hormones.

What Is the Thyroid Gland?

The thyroid gland is a small and vascular endocrine gland that is shaped like a butterfly. The glands consist of two lobes connected by a band of tissues known as the isthmus. Both the lobes of the gland are present below the voice box and on both sides of the windpipe. The thyroid gland's main function is the production and secretion of the thyroid hormone; thyroxine (T4), triiodothyronine (T3), and calcitonin. These hormones have an important role in childhood growth, brain development, and protein synthesis. Iodine is required for the synthesis of thyroid hormones. Thyroid problems such as hyperthyroidism, hypothyroidism, Grave's disease, thyroid nodule, goiter, and others are commonly encountered.

What Is a Goiter?

A goiter is a lump or swelling in the neck caused by an enlarged thyroid gland. The thyroid gland is normally not visible; however, with goiter, the gland enlarges and develops a lump that is easily noticeable. Iodine deficiency is responsible for over ninety percent of goiter occurrences worldwide. Most goiters are benign (noncancerous), and just a few are malignant (cancerous).

What Are the Types of Goiter?

Goiters are classified into two types:

1. Nodular Goiter: When solid or fluid-filled lumps develop within the thyroid gland, this condition is called nodular goiter. These nodules grow at different rates and secrete thyroid hormones. Inactive nodules may be malignant.

2. Diffuse Goiter: The whole thyroid gland swells and feels smooth due to hyperplasia (increased cell multiplication leading to organ or tissue growth) in the case of diffuse goiter.

Goiters are also classified based on their size as,

1. Class I: Goiters cannot be typically seen and only be felt on palpation.

2. Class II: Goiter is palpable and also seen.

3. Class III: Goiter is massive, and palpation results in compression marks.

What Is a Toxic Multinodular Goiter?

A toxic multinodular goiter is a hormonally active multinodular goiter with hyperthyroidism. It is characterized by the excess production of thyroid hormones from functionally active thyroid nodules. These nodules do not require stimulation from thyroid-stimulating hormones secreted by the pituitary gland. Toxic multinodular goiter is the second most common cause of hyperthyroidism and is prevalent in older adults. Toxic multinodular goiter has been reported to affect individuals over sixty years of age, and it is more common in women as compared to men (like any other thyroid disease). Toxic multinodular goiter may consist of more than one autonomous thyroid nodule, multiple autonomous thyroid nodules, non-autonomous thyroid nodules, or multiple small autonomous areas associated with hyperthyroidism of various degrees. Autonomous nodules are hyperactive or hot nodules, and non-autonomous nodules are inactive or cold nodules.

What Are the Other Names of Toxic Multinodular Goiter?

Alternative names of toxic multinodular goiter are:

• Plummer disease.

• Thyrotoxicosis-nodular goiter.

• Overactive thyroid-toxic nodular goiter.

• Multinodular toxic goiter.

• Toxic nodular goiter.

What Causes Toxic Multinodular Goiter?

Toxic multinodular goiter mostly initiates from pre-existing simple goiter. The goiter may occur due to intermittent stimulus, which can occur due to physiologic or pathologic reasons. Chronic stimuli lead to diffuse enlargement of the thyroid gland (thyroid hyperplasia), which leads to the formation of a nodule or multiple nodules, followed by activation of the nodules. These nodules or growths are generally benign (non-cancerous). Certain factors contribute to the development of the disease. The primary factors include; the functional state of normal follicular cells of the thyroid gland and the genetic inheritance of the condition from parents to their children. Secondary factors include elevation in the thyroid-stimulating hormone levels, stress, use of certain medications, etc.

What Are the Symptoms of Toxic Multinodular Goiter?

Symptoms of toxic multinodular goiter are very similar to hyperthyroidism because of the associated hyperthyroidism with the condition. Common symptoms of toxic multinodular goiter include:

• Unusual weight loss.

• Intolerance towards heat.

• Shaking and tremors.

• Palpitations.

• Increased heart rate (tachycardia).

• Increased bowel frequency.

• Irregular menstrual cycles.

• Excessive sweating.

Less common symptoms of toxic multinodular goiter include:

• Atrial fibrillation (irregular and rapid heartbeat that may cause blood clots in the heart).

• Osteoporosis (a condition where bones become weak and brittle) leads to frequent fractures.

• Decreased sex drive.

• Involuntary urination in children (enuresis).

• Lid lag and stare.

• Muscle wasting.

Symptoms occurring exclusively due to goiter:

• Shortness of breath (dyspnea).

• Difficulty in swallowing (dysphagia).

• Hoarseness of voice.

• Compression of the trachea (windpipe).

Symptoms that are seen in older adults:

• Fatigue and weakness.

• Chest pain or pressure on the chest.

• Changes in mood and loss of memory.

How Is Toxic Multinodular Goiter Diagnosed?

The diagnosis of toxic multinodular goiter is made with the help of blood examinations and imaging tests. Blood examinations and laboratory findings include:

• Thyroid Function Test: The thyroid function test will show decreased thyroid-stimulating hormone levels and increased levels of thyroxine (T3) and triiodothyronine (T4) hormones.

• Complete Blood Count: This test is done to see any variations in the levels of red blood cells, white blood cells, platelets, hemoglobin, etc. A complete blood count will detect a wide range of disorders and evaluate overall health. A complete blood count may be done along with liver function before starting the medications for the treatment of toxic multinodular goiter.

• Other Blood Tests: Other blood tests include anti-thyroid peroxidase, antithyroglobulin antibodies, thyroid-stimulating immunoglobulins, etc.

Imaging tests that are done to confirm the diagnosis of toxic multinodular goiter are:

• Ultrasound: It is done to evaluate the number, size, and location of the nodules.

• Color Doppler: It is a type of ultrasound used to determine the vascularity of the nodules.

• CT (Computed Tomography) Scan and MRI (Magnetic Resonance Imaging): These are done to study the anatomical and structural details of the goiter and thyroid nodules (especially retrosternal-below the breast bone and recurrent thyroid enlargement).

• Thyroid Scintigraphy: This test uses radioactive iodine, and the scan will show localized radioactive iodine uptake by the nodules and decreased uptake by the thyroid tissues in the background. Thyroid scintigraphy is the definitive test that confirms toxic multinodular goiter and eliminates the chances of other thyroid disorders that may lead to hyperthyroidism.

• Fine Needle Aspiration Cytology: This is a kind of biopsy done with the help of a fine and hollow needle inserted into the lesion to get a small portion of the tissue to view under a microscope. In this test, multiple tissue samples are collected and tested for the presence of any malignancy in the nodules.

What Is the Treatment for Toxic Multinodular Goiter?

Apart from the treatment of clinical hyperthyroidism and symptomatic treatment of the patient, the definitive treatment of toxic multinodular goiter includes surgery and radioactive iodine.

• Surgery: Total or near-total thyroidectomy may be done depending upon the severity of the disease. The patient will have post-surgical hypothyroidism. And the possible complications of the surgery include; vocal cord paralysis, hypoparathyroidism, tracheostomy, post-operative bleeding, infections, etc.

• Radioactive Iodine Ablation: It is the definitive treatment of toxic multinodular goiter with no contraindications except for pregnancy. The dose of iodine is custom calculated for each patient, and the use of a single dosage for every patient is no longer employed. The possible complications of the treatment include; hypothyroidism, thyrotoxic symptoms that may be mild, thyroid storm, tracheal compression, etc. The size of the nodule may be significantly reduced after radioactive iodine ablation, but it does not entirely go away as in the case of surgery.

• Antithyroid Drugs: Anti-thyroid drugs like Propylthiouracil and Methimazole are commonly used to treat hyperthyroidism while waiting for radioactive iodine ablation and before surgery (to prepare for the surgery).

What Is the Difference Between a Toxic Nodule and a Toxic Multinodular Goiter?

Toxic Nodule: A single nodule makes an extra amount of thyroid hormone. A single nodule is often known as a toxic adenoma.

Toxic Multinodular Goiter: Multiple nodules lead to an excess amount of thyroid hormone. In multinodular goiter, some nodules may be non-toxic and inactive.

What Are the Possible Complications of Toxic Multinodular Goiter?

Possible complications of toxic multinodular goiter are:

• Heart failure.

• Irregular heartbeat.

• Rapid heartbeat.

• Bone loss.

• A thyroid crisis or thyroid storm (a life-threatening condition associated with untreated hyperthyroidism) may cause abdominal pain, fever, and decreased mental alertness.

Conclusion:

Toxic multinodular goiter or Plummer disease is a common cause of hyperthyroidism and occurs due to multiple reasons. The diagnosis and treatment of the condition are definitive and effective. In addition, the prognosis of toxic multinodular goiter is excellent, with very few complications. However, older patients with other systemic problems may have more complications and recurrence. But the complications are easily treatable with medication. The development of toxic multinodular goiter can be easily prevented by keeping a check on hyperthyroidism and treating simple goiter before the condition progresses.