Hypothyroidism

Definitions & Key takeaways

Hypothyroidism refers to a condition where there's a lack of thyroid hormones (triiodothyronine (T3) and thyroxine (T4)), which normally help control the body's metabolism.

Hypothyroidism can be primary or secondary. In primary hypothyroidism, the thyroid gland isn't working properly, because of an autoimmune disease like Hashimoto's thyroiditis, hyperthyroidism treatment, or a congenital defect. In secondary hypothyroidism, either the anterior pituitary gland or the hypothalamus is the problem, usually because of a tumor or damage from surgery.

Symptoms of Hypothyroidism include weight gain, mental slowness, swelling in the skin and soft tissues, and a slower heart rate.

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Introduction0:00–0:15

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.

Physiology0:15–2:07

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!

Pathology2:07–3:04

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.

Primary hypothyroidism3:04–4:58

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 iodine, 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.
Primary hypothyroidism can also happen after treatment for hyperthyroidism, either because the surgery removes part or all of the thyroid gland or because radioiodine therapy damages too many follicular cells.
Another type of primary hypothyroidism is when it affects a newborn, in which case it’s called congenital hypothyroidism.
Most of the time it’s sporadic - meaning it occurs at random - but it can also be caused by an inherited genetic mutation.
Ultimately, the newborn’s thyroid gland doesn’t make enough thyroid hormones either because it doesn’t develop normally - the gland can be absent, underdeveloped, or develop in the wrong place in the body - or because there’s a defect within a normal-looking thyroid gland that affects its ability to make thyroid hormones.

Secondary and tertiary hypothyroidism4:58–5:23

Now in secondary hypothyroidism, also called central hypothyroidism, the issue is that the body doesn’t produce enough TSH.
It typically happens because there’s a tumor in the anterior pituitary which compresses the gland and prevents TSH production, or because there’s damage to the hypothalamus from tumors or trauma which decreases thyrotropin-releasing hormone production.

Symptoms5:23–6:30

The symptoms of hypothyroidism, which can take years before they are even recognized, include weight gain despite a loss in appetite because of the lower basal metabolic rate; cold sensitivity because the body is producing less heat; and slower heart rate, mental slowness, lethargy, and constipation because of the decreased effect of thyroid hormones on the sympathetic nervous system.
Accumulation of glycosaminoglycans also cause myxedema, or swelling, in the skin and soft tissues like the tongue. If the hypothyroidism is caused by Hashimoto thyroiditis, there can be a goiter - which is an enlarged thyroid gland - because of the hypertrophy and hyperplasia of the gland.
Babies with congenital hypothyroidism will have symptoms related to the decreased metabolic rate like excessive sleeping.
But if the condition isn’t detected quickly enough, they are at risk for mental retardation and irreversible intellectual disabilities, delayed physical growth, and shortened height because of the role of thyroid hormones in brain and sympathetic nervous system development.

Myxedema coma6:30–6:52

There is also a severe, life-threatening form of hypothyroidism called myxedema coma which affects people with poorly managed hypothyroidism who undergo a stressful situation - like a serious infection or surgery.
All of the normal symptoms of hypothyroidism become exaggerated - for example mental slowness turns into altered consciousness and confusion, and decreased body temperature turns to hypothermia.

Diagnosis6:52–7:24

Diagnosing hypothyroidism is done by measuring blood levels of TSH, T3, and T4. In all cases, thyroid hormones will be low, but TSH levels vary - if it’s due to a primary cause, TSH will be high and if it’s due to a secondary cause, TSH will either be low or normal.
Because congenital hypothyroidism can be hard to detect in newborns, many countries screen all newborns for congenital hypothyroidism within the first few weeks of life.

Treatment7:24–7:33

Treatment for all types of hypothyroidism is thyroid hormone replacement therapy, primarily using synthetic T4. All right, as a quick recap, hypothyroidism refers to a condition where there’s a lack of thyroid hormones.

Review7:33–8:14

In primary hypothyroidism, the thyroid gland isn’t working properly, as a result of autoimmune disease like Hashimoto thyroiditis, hyperthyroidism treatment, or a congenital defect.
In secondary hypothyroidism, either the anterior pituitary gland or the hypothalamus is the problem, usually because of a tumor or damage from surgery.
In all cases, the lack of thyroid hormones can cause a decreased metabolic state, with symptoms like weight gain, mental slowness, swelling in the skin and soft tissues, and a slower heart rate.