Plummer’s Disease: Pathophysiology, Epidemiology, Symptoms and Treatment


Plummer’s disease, also called toxic multinodular goiter, is a thyroid condition characterized by a marked increase in the thyroid gland (goiter), firm thyroid nodules, and overproduction of thyroid hormone (hyperthyroidism).

The toxic multinodular goiter was first described in 1913 by Dr. Henry Plummer. A goiter means an enlarged thyroid gland; a nodule is a growth inside the thyroid gland that is often benign; in rare cases, it can be malignant.

Plummer’s disease, which usually occurs in older people, is of unknown etiology. Its symptoms resemble those of hyperthyroidism with swelling of the thyroid gland.

Toxic nodular goiter (or Plummer’s disease, the other name for a toxic nodular goiter) is less common than Graves’ disease. Its prevalence increases with age and in the presence of iodine deficiency.

The disease usually progresses. With toxic nodular goiter, medical therapy is not as helpful as Graves’ disease.

Once the diagnosis is made, the treating physician and the patient should discuss each treatment option, including logistics, benefits, expected recovery speed, inconveniences, side effects, and costs.


Patients with toxic multinodular ganglionic goiter or solitary toxic nodule are better treated with I-131 therapy or thyroidectomy (according to the recent guidelines of the American Thyroid Association ). Still, treatment may be appropriate in some cases—prolonged treatment at low doses with Methimazole.

The benefits of surgery would include a rapid recovery from the disease and the absence of toxic effects from medical therapy or radioactive iodine therapy.

The disadvantage to surgical therapy would include the small 1% in the hands of a surgeon’s experience, the rate of complications, and the presence of a small scar.

These would include a 1% hoarseness rate (vocal cord nerve injury), a 1% low calcium level, and a 0.5% bleeding or infection rate.

In the hands of the experienced thyroid surgeon, the side effects are minimal, and the scar is tiny, the opposite of the surgeon with little experience when the complication rate could approach 10%.

Typically, people affected by Plummer’s disease develop many goiter years before the onset of hyperthyroidism symptoms; Most patients are more than 50 years old before the characteristic accelerated heart rate and other heart conditions appear.

Unlike Graves’ disease, Plummer’s disease rarely causes bulging of the eyes (exophthalmos). Inflammation of the thyroid gland can obstruct breathing or swallowing, requiring surgery to remove excess tissue; Cardiac symptoms can result in congestive heart failure.

In the absence of obstruction or cosmetic reasons to remove the gland, the goiter can be treated with drugs that block thyroid activity or radioactive iodine therapy; however, the multiple thyroid nodules characteristic of the disease may raise the suspicion of cancer, necessitating the surgical removal of the gland.


The symptoms of hyperthyroidism in a toxic nodular goiter are usually minimal. In the elderly, the only symptoms may be a new onset of atrial fibrillation or congestive heart failure.

Rarely a nodular goiter can cause some pressure symptoms, such as compression in the windpipe, difficulty swallowing, or hoarseness.

It differs from Graves’ disease in that extra thyroid manifestations, and thyroid autoantibodies are absent.

Approximately 80% of patients with nodular goiter are chemically euthyroid at the initial presentation.

In young people, thyrotoxicosis is considered weight loss, anxiety, insomnia, and heat intolerance.

Atrial fibrillation in an enlarged goiter is often the only finding in the elderly.

Symptoms of dysphagia, hoarseness, dyspnea, stridor, and cough may indicate a retrosternal or intrathoracic nodular effect.

This may be due to the limited capacity of the nodules to oxidize iodide or may be due to their preponderance in areas with a relatively low iodine intake.

The toxic nodular goiter represents less than 5% of the cases of thyrotoxicosis in the presence of sufficient iodine, but almost half of the patients with iodine deficiency.

Coexisting cancer is more familiar with nodules that do not work and is more likely in men.


A toxic nodular goiter (BNT) is a thyroid gland that contains thyroid nodules that function autonomously, with resultant hyperthyroidism.

There are different considerations if the patient has a single solitary toxic nodule (see Solitary thyroid nodule). BNT, or Plummer’s disease, was first described by Henry Plummer in 1913.

BNT is the second most common cause of hyperthyroidism in the Western world, after Graves’ disease. In the elderly and areas of endemic iodine deficiency, BNT is the most common cause of hyperthyroidism.


Nodular goiter (BNT) represents a spectrum of diseases ranging from a single hyperfunctioning nodule (toxic adenoma) within a multinodular thyroid to a gland with multiple areas of hyperfunction.

The natural history of a multinodular goiter implies a variable growth of individual nodules; This can progress to hemorrhage and degeneration, followed by healing and fibrosis.

Calcification can be found in areas of the previous hemorrhage. Some nodules can develop the autonomous function.

Autonomic hyperactivity is conferred by somatic mutations of thyrotropin, thyroid-stimulating hormone (TSH), receptor in 20-80% of toxic adenomas, and some multinodular goiter nodules.

Autonomic functioning nodules can become toxic in 10% of patients. Hyperthyroidism occurs predominantly when the individual nodules are more than 2.5 cm in diameter. The signs and symptoms of BNT are similar to those of other types of hyperthyroidism.


  • In the United States

Nodular goiter accounts for approximately 15-30% of cases of hyperthyroidism in the United States, only after Graves’ disease.

  • On an international level

In areas of endemic iodine deficiency, toxic nodular goiter (BNT) accounts for approximately 58% of cases of hyperthyroidism, 10% of which come from solitary poisonous nodules.

Graves’ disease represents 40% of cases of hyperthyroidism. In patients with underlying nontoxic multinodular goiter, the initial administration of iodine (or iodinated contrast agents) can lead to hyperthyroidism (Jod-Basedow effect).

Iodinated drugs, such as amiodarone, can also induce hyperthyroidism in patients with underlying nontoxic multinodular goiter. Approximately 3% of patients treated with amiodarone in the United States (more in areas of iodine deficiency) develop amiodarone-induced hyperthyroidism.

Morbidity and mortality

The morbidity and mortality due to toxic nodular goiter can be divided into problems related to hyperthyroidism and issues associated with the growth of the nodules and the gland.

Local compression problems due to the growth of nodules, although unusual, include dyspnea, hoarseness, and dysphagia. Both TNG and Graves disease have increased mortality, but for different reasons.

It is more common in older adults; Therefore, complications due to comorbidities, such as coronary heart disease, are significant in managing hyperthyroidism.


Nodular goiter occurs more commonly in women than in men. In women and men over 40 years of age, the prevalence rate of palpable nodules is 5-7% and 1-2%, respectively.


The majority of patients with toxic nodular goiter are older than 50 years. Thyrotoxicosis often occurs in patients with a history of long-standing goiter.

Toxicity occurs in a subset of patients who develop an autonomous function. This toxicity usually reaches a maximum in the sixth and seventh decade of life, especially in people with a family history of multinodular goiter, suggesting a genetic component.


There are three main classes of therapy in treating Graves’ disease: antithyroid drugs, radioactive iodine ablation, and subtotal thyroidectomy.

Antithyroid drugs have not been widely accepted in treating Plummer’s disease because they are less effective, and life-long therapy would be necessary.

Unlike the usual spontaneous remission of Graves’ disease, hyperthyroidism or toxic nodular goiter continues indefinitely.

Its use (antithyroid drugs) is recommended only as an adjuvant when necessary for the initial control of hyperthyroidism.

Radioiodine therapy is inferior to the role it plays in Graves’ disease because toxic nodular goiter often persists after treatment.

The goal of radiotherapy in Plummer’s disease is to destroy the autonomic tissue and restore euthyroidism.

Erickson and associates evaluated the medical records of 253 patients treated for toxic nodular goiter between 1975 and 1993.

Of those treated with radioactive iodine, 20% required a second treatment, unlike those treated with surgery, which did not require a second treatment.

In the report by Erickson and associates, half of the patients treated surgically had achieved success in 3 days for surgical treatment versus three months for treatment with radioactive iodine.

Similar results were found in a report by Jensen and his colleagues. The dose of radioactive iodine is variable, and several of these may be necessary. Assimilation is often relatively low, so high doses are needed up to almost double those administered to Graves’ patients for successful treatment.

Radioactive iodine therapy in large nodular goiters that extend substernal puts patients at risk for radiation-induced thyroiditis that, although rare, can cause acute thyroid enlargement and compression of the airways.