In hypothyroidism, ‘hypo' refers to having too little, and ‘thyroid’ refers to thyroid hormone, so hypothyroidism refers to a condition where there’s a lack of thyroid hormones.
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 cell’s basal metabolic rate.
So as an example, the cell 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 can be really useful when you need a boost to get through the final rounds of a sporting competition or when you’re trying to stay warm during a snowstorm!
Now, hypothyroidism can happen a few different ways - and all of them result in a lack of thyroid hormones and a decreased basal metabolic rate, where cellular reactions are happening slower than normal.
There are two types of hypothyroidism - primary and secondary.
In primary hypothyroidism, the thyroid gland is the problem, because it isn’t making enough thyroid hormones.
Not only is there a lack of T3 and T4 which causes a slowing down of metabolic processes, but there are increased levels of TSH from the pituitary to try to stimulate the gland.
A secondary effect of the high levels of TSH is that it stimulates fibroblasts in the skin and soft tissues.
The stimulated fibroblasts start depositing glycosaminoglycans - extracellular matrix proteins - in the interstitium - the space between cells.
Iodine deficiency is the most common cause of primary hypothyroidism in low income countries that don’t fortify foods with iodine. That’s because the follicular cells don’t have the iodine they need to produce T3 and T4.
In countries that do fortify foods with iron, the most common cause of primary hypothyroidism is Hashimoto thyroiditis, an autoimmune disorder where T cells and autoantibodies like anti-thyroid peroxidase and antithyroglobulin infiltrate the thyroid.
Damage to some parts of the thyroid, and the subsequent increase in TSH, leads to thyroid hypertrophy and hyperplasia.
In other words, the thyroid responds to autoimmune damage by increase in the size and number of healthy follicular cells, both of which causes the thyroid to enlarge.
Unfortunately this compensation is short-lived and eventually the autoantibodies cause so much follicular cell damage that they destroy thyroid function altogether.