Toxic multinodular goiter

Also known as toxic nodular goiter, toxic nodular struma, or Plummer’s disease is a multinodular goiter associated with a hyperthyroidism.

Common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH).

It is the second most common cause of hyperthyroidism, after Graves’ disease.

Risk factors for toxic multinodular goiter include individuals over 60 years of age and being female.

Activating mutations in the TSH receptor gene is the underlying mechanism resulting in increased adenylyl cyclase production independent of TSH.

It is more common in iodine-deficient areas.

Apathetic thyrotoxocosis is encounteted up to 15% of elderly patients in whom hyperthyroidism develops, regardless of cause, absent symptoms of hyperthyroidism in the presence of new onset cardiac symptoms of heart failure and arrhythmias, cognitive changes, hypercalcemia, weakness, and lethargy.

Symptoms of toxic multinodular goitre are similar to that of hyperthyroidism, including:

heat intolerance

muscle weakness/wasting





weight loss


increased appetite

non-painful goiter


Iodine deficiency leading to decreased T4 production.

Induction of thyroid cell hyperplasia due to low levels of T4, accounts for the multinodular goiter appearance.

Increased replication predisposes to a risk of mutation in the TSH receptor.

If the mutated TSH receptor is constitutively active, it would then become ‘toxic’ and produces excess T3/T4 leading to hyperthyroidism.

Toxic multinodular goiter can be treated with antithyroid medications such as propylthiouracil or methimazole, radioactive iodine, or with surgery.



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