Toxic multinodular goiter

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. 

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! 

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.