Conditions: Toxic Hyperfunctioning Thyroid Nodule

(also known as toxic adenoma)

A toxic hyperfunctioning thyroid nodule, also called a toxic adenoma, is a benign tumor of thyroid that produces thyroid hormone in excess of the body’s needs and in an autonomous fashion. In other words, a toxic adenoma produces thyroid hormone in toxic levels causing symptoms of hyperthyroidism, and the nodule itself does not respond appropriately to negative feedback of low TSH.

A number of factors seem to contribute to the development of a toxic adenoma. Some families appear to share a genetic predisposition to this problem. Low iodine intake (typically in regions of the world with low iodine and the absence of iodine supplementation in table salt) is another factor. New genetic mutations, which occur continuously and randomly throughout life, may also play a role when a specific mutation in a thyroid cell happens to affect the molecular mechanism of regulating thyroid hormone output.

At an early stage in the disease process, before a person has become hyperthyroid, when a nodule that produces thyroid hormone autonomously (that is, without respect to negative feedback) is small, the total amount of thyroid hormone produced by this rogue hyperfunctioning nodule is not in excess of the body’s needs. The remaining portion of the thyroid gland, responding appropriately to the feedback system, adjust its thyroid hormone output so that the total thyroid hormone produced from the thyroid is within the normal range or perhaps minimally high. Over time, an autonomously functioning nodule may grow and produce an amount of thyroid hormone that significantly exceeds the total body requirements, even when the remainder of the thyroid gland is fully suppressed and making no additional thyroid hormone. When body tissues receive excessive thyroid hormone exposure, problems arise (toxicity) in the form of hyperthyroidism. This concept fits with the observation that toxic nodules tend to be greater than 3 cm in size, and tend to occur more commonly with increasing age.

As with all thyroid nodules, hyperfunctioning thyroid nodules are more common in women than in men,

How is a toxic adenoma diagnosed?

After initial evaluation with history and physical exam, and once a person has been confirmed to be hyperthyroid based on blood testing, a thyroid ultrasound may be undertaken. When a single thyroid nodule is found, a diagnostic radioiodine thyroid uptake scan may be undertaken. A toxic adenoma has a characteristic finding on this imaging study.

Do toxic adenomas require fine needle aspiration biopsy?

No. Interestingly, toxic adenomas have an extremely low rate of being cancerous. Because of this, identification of a toxic hyperfunctioning nodule essentially removes suspicion of cancer within it and therefore yields no reason to perform fine needle aspiration on it. In the rare cases in which a toxic adenoma might be cancerous, a fine needle aspiration would still be unable to distinguish a benign follicular adenoma from a follicular carcinoma.

treatment

Antithyroid drugs (propylthiouracil and methimazole) may be used temporarily to treat a toxic hyperfunctioning nodule, but these drugs are not usually used for longer-term management because of the risks associated with these medicines and the need for lifelong therapy given the lack of cure achieved by these drugs.

Common treatment options for a toxic hyperfunctioning nodule include the following:

1. Radioiodine ablation

2. Injury to the nodule with a minimally invasive technique

3. Surgical removal of the nodule

These are discussed below.

Radioiodine ablation

Radioactive iodine, also termed radioiodine, may be used in lower doses for a diagnostic scan or in higher doses for a treatment effect. In the case of a toxic adenoma, a treatment dose of radioactive iodine may be used in an effort to damage and decrease thyroid hormone function from the toxic adenoma. This may be effective, but this treatment strategy is sometimes imperfect.

One risk of using radioactive iodine to treat a toxic adenoma is that eventual hypothyroidism may develop. This may be because of the damage that the radioactive iodine incurred on the normal portion of the thyroid gland or it may be due to radioactive iodine causing the development of thyroid autoantibodies, in essence creating Hashimoto’s thyroiditis and eventual hypothyroidism.

Efforts to minimize the damaging effect of radioactive iodine on the normal portion of the gland involve giving a patient thyroid hormone supplements prior to use of radioactive iodine. This has the effect of suppressing the normal thyroid gland and making it less able to take in iodine when the radioactive iodine is given.

Another risk of using radioactive iodine to treat a toxic adenoma is that the radioiodine effect may not be adequate to impair thyroid hormone output from the toxic adenoma, with ongoing hyperthyroidism. In this case, a second attempt at using radioactive iodine may occur, or surgery may be undertaken to remove the toxic adenoma. In the case of surgery being used as a backup, however, the patient has an increased risk of hypothyroidism. In about 5% of patients treated with radioactive iodine for similar conditions—toxic or euthyroid multinodulare goiter—develop antibodies against the TSH receptor, which is the cause of Graves’ disease hyperthyroidism.

Overall, the use of radioactive iodine to treat a toxic adenoma is a common undertaking, but is imperfect in that the end result may be persistent hyperthyroidism or the opposite problem, hypothyroidism.

Injury to the nodule with a minimally invasive technique

More recently, efforts to damage a toxic adenoma without radioactive iodine and without surgery have gained interest. One treatment method is to inject the toxic adenoma with ethanol under ultrasound guidance. This results in blockage of small blood vessels feeding the adenoma as well as direct injury to the cells within the toxic adenoma. An expected side effect is pain and a complication of recurrent laryngeal nerve injury has been reported. Nevertheless, about 85% of patients treated in this manner for a toxic adenoma achieved a euthyroid state after 12-30 months.

Similarly, using a needle that can deliver heat by a laser to a toxic adenoma has been described, with variable effectiveness in achieving euthyroidism.

With any minimally invasive technique, however, repeat blood draws to check for hyperthyroidism and hypothyroidism are necessary, especially in patient who develop circulating thyroid autoantibodies after treatment.

Surgical removal of the nodule

Removal of a toxic adenoma by partial thyroidectomy results in a rapid and permanent cure of hyperthyroidism with a very low complication rate.

Avoidance of thyroid storm as a complication of thyroid surgery is accomplished with antithyroid beta-blocker medications.

After removal of the toxic adenoma, the remaining, normal portion of the thyroid gland usually adjusts output, based on normal feedback mechanisms, to produce adequate thyroid hormone for the individual’s needs. It is uncommon, but not impossible, that the remaining thyroid gland cannot produce adequate thyroid hormone, and in this case, supplemental thyroid hormone is given.