Toxic multinodular goiter

Definitions & Key takeaways

Toxic multinodular goiter (TMNG) is a condition characterized by the growth of multiple nodules in the thyroid gland, which can cause the gland to become enlarged and produce too much thyroid hormone. The excess thyroid hormone production can lead to symptoms of hyperthyroidism, including weight loss, rapid heart rate, tremors, and heat intolerance.

TMNG typically develops after prolonged iodine deficiency, which causes hypertrophy and hyperplasia of the thyroid gland. Continued follicular cell division can lead to a genetic mutation of the TSH receptor turning a non-toxic multinodular goiter into a toxic multinodular goiter.

Symptoms include an enlarged thyroid as well as the typical symptoms of hyperthyroidism like weight loss, a rapid heart rate, and hyperactivity. The treatment for TMNG involves medications like beta-blockers and radioactive iodine, or surgery to remove part or all of the thyroid gland.

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Introduction0:00–0:29

In toxic multinodular goiter, also called Plummer’s disease, ‘toxic’ refers to something harmful, ‘nodular’ refers to little lumps or nodules of tissue, and ‘goiter’ refers to a large thyroid gland.
So toxic multinodular goiter is a condition where the thyroid gland enlarges and is filled with lots of little nodules of tissue - each of which produce so much thyroid hormone that it becomes harmful to the body.

Physiology0:29–2:21

Normally, the hypothalamus, which is located at the base of the brain, detects low blood levels of thyroid hormones and releases thyrotropin-releasing hormone into the hypophyseal portal system - which is a network of capillaries linking the hypothalamus to the anterior pituitary.
The anterior pituitary then releases thyroid-stimulating hormone, also called thyrotropin or simply TSH. TSH stimulates the thyroid gland which is a gland located in the neck that looks like two thumbs hooked together in the shape of a “V”.
The thyroid gland is made up of thousands of follicles, which are small spheres lined with follicular cells. Follicular cells convert thyroglobulin, a protein found in follicles, into two iodine-containing hormones, triiodothyronine or T3, and thyroxine or T4.
Once released from the thyroid gland, these hormones enter the blood and bind to circulating plasma proteins. Only a small amount of T3 and T4 will travel unbound in the blood, and these two hormones get picked up by nearly every cell in the body.
Once inside the cell T­4 is mostly converted into T3, and it can exert its effect. T3 speeds up the basal metabolic rate.
So as an example, they might produce more proteins and burn up more energy in the form of sugars and fats. It’s as if the cells are in a bit of frenzy.
T3 increases cardiac output, stimulates bone resorption - thinning out the bones, and activates the sympathetic nervous system, the part of the nervous system responsible for our ‘fight-or-flight’ response.
Thyroid hormone is important - and the occasional increase is like getting a boost to fight off a hungry predator or to stay warm during a snowstorm!

Pathology2:21–4:49

Toxic multinodular goiter usually starts with a chronic lack of dietary iodine, and follicular cells need iodine to make T3 and T4.
With less iodine around, each follicular cell makes less thyroid hormone, and as a whole, the level of thyroid hormone goes down.
In response to low levels of thyroid hormones, the anterior pituitary releases TSH. The high levels of TSH cause thyroid hypertrophy - the build up in thyroid tissue - and hyperplasia - increased numbers of follicular cells.
But, here’s the thing - some parts of the thyroid gland are more responsive to TSH than others, so the growth ends up being uneven throughout the thyroid.
So the most responsive follicular cells start to grow quickly and develop into a nodule, and the rest of the gland looks basically the same.
Typically, multinodular goiter starts with a single nodule and over years multiple nodules start to appear. This strategy works for a while and the thyroid is considered a non-toxic multinodular goiter.
In other words, having more follicular cells makes up for the fact that each follicular cell makes less thyroid hormone - so the thyroid enters a balanced or euthyroid state.
So at this point the TSH levels go down even though there’s an iodine deficiency. But if the iodine deficiency worsens, there’s another round of increased TSH which stimulates more thyroid growth.
Over time, the thyroid gland goes through many cycles of growth and then a period of balance. Now, a non-toxic multinodular goiter becomes toxic when a genetic mutation occurs in one of the dividing follicular cells, in particular when the mutation affects the TSH receptor.
If the mutation causes the TSH receptor to be constantly “on”, then the affected cell might constantly remain stimulated to divide and produce thyroid hormone.
At this point, it develops into a toxic nodular goiter. Even when thyroid hormone levels rise and TSH production is shut down, these independent nodules use any available iodine to make thyroid hormone - well beyond what the body wants or needs.
The result is that cells across the body are in a state of hypermetabolism, where cellular reactions are constantly happening at a faster pace than normal.

Symptoms4:49–6:20

Symptoms of toxic multinodular goiter are related to enlargement of the thyroid gland and to hyperthyroidism. The enlarged thyroid gland can put pressure on the other structures in the neck, obstructing the airway and making swallowing difficult.
It can compress nerves, like the superior or recurrent laryngeal nerves, which will make the voice hoarse. It can also cause superior vena cava syndrome by limiting blood flow in the superior vena cava, which results in facial and arm swelling because blood gets backed up in the veins of the head and upper body.
Hyperthyroidism causes weight loss despite an increase in appetite because of the higher basal metabolic rate; heat intolerance because the body is producing more heat;and rapid heart rate, sweating, hyperactivity, anxiety and insomnia because of the effect of thyroid hormones on the sympathetic nervous system.
Sympathetic overstimulation of muscles that control eye movements also makes the eyes appear more open than normal, so you see more of the “white” of the eyes.
Thyroid storm, a life-threatening complication of hyperthyroidism where the body goes into a state of severe hypermetabolism, can develop when someone with hyperthyroidism stops their treatment, develops an infection, or has surgery.
All of the normal symptoms of hyperthyroidism become exaggerated - for example heat intolerance turns to high fever and rapid heart rate turns to cardiac arrhythmia.

Diagnosis6:20–6:40

Diagnosing toxic multinodular goiter involves confirming hyperthyroidism by measuring blood levels of thyrotropin, T3, and T4 and confirming the presence of multinodular goiter through ultrasonography.
A radioiodine uptake test can help identify independent nodules. The treatment for toxic multinodular goiter symptoms is usually done with beta-blockers; and surgery can be used to remove part or all of the thyroid gland.

Treatment6:40–7:22

Another option, radioiodine therapy involves taking oral doses of radioactive iodine, which is absorbed by active follicular cells and over time damages them.
This destroys hyperfunctioning nodules within the thyroid gland, because radioiodine gets preferentially picked up by those nodules, leaving the rest of the gland intact.
The long-term use of thioamides, anti-thyroid drugs which block thyroid hormone production and secretion, is typically only used when radioiodine therapy and surgery are not appropriate options.

Review7:22–8:02

All right, as a quick recap, toxic multinodular goiter is a condition where the thyroid gland develops independently functioning nodules which results in hyperthyroidism.
It develops after prolonged iodine deficiency, which causes hypertrophy and hyperplasia of the thyroid gland. Continued follicular cell division can lead to a genetic mutation of the TSH receptor turning a non-toxic multinodular goiter into a toxic multinodular goiter.
Symptoms include an enlarged thyroid as well as the typical symptoms of hyperthyroidism like weight loss, a rapid heart rate, and hyperactivity.