Hypothyroidism medications

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Introduction0:00–0:26

In hypothyroidism, ‘hypo’ refers to having too little, and ‘thyroid’ refers to thyroid hormones, so hypothyroidism refers to a condition where there’s not enough thyroid hormones.
Now, as treatment for hypothyroidism, we can use medications that boost thyroid hormone synthesis, or we can thyroid hormone analogues as a replacement.

Physiology0:26–4:48

There are 2 different thyroid hormones; triiodothyronine or T3, and thyroxine or T4. They’re two tyrosine-based, iodine-containing hormones that are secreted by the thyroid gland, which is located anteriorly in the neck and consists of two lobes that look like two thumbs hooked together in the shape of a “V”.
Now, if we zoom into the thyroid gland, we’ll find thousands of follicles, which are small hollow spheres whose walls are lined with follicular cells or thyrocytes.
Zooming in, these follicular cells have an apical side that surrounds a central lumen filled with a viscous fluid called the colloid.
The colloid contains the precursor hormone thyroglobulin. The basolateral side of follicular cells is in contact with blood vessels that supply these cells.
Now, synthesis of thyroid hormones inside the follicles involves a few important steps. First, the inorganic iodide ions, present in a low concentration in the blood, are actively taken up by the basolateral side of the follicular cells, along with two sodium ions, via a sodium- iodide symporter.
This step is known as ‘iodide trap’. The iodide ion is then pumped into the colloid via the pendrin protein, where it undergoes oxidation with the enzyme “thyroid peroxidase” or TPO, which changes it into an organic iodine atom.
It’s then attached to tyrosine amino acid residues which are found throughout thyroglobulin. This step is known as iodination.
Some tyrosine residues are bound by only one iodine, whereas others are bound by two iodine atoms, yielding monoiodotyrosine or MIT, and diiodotyrosine or DIT, respectively.
These molecules are then coupled together by the same enzyme “thyroid peroxidase” or TPO. This process is known as coupling.
Coupling one MIT with one DIT creates T3, while linking two DIT molecules creates T4. In general, T4 is created in greater amounts than T3.
T3 is the more active form with a half life of one to two days, while T4 is the less active form with a longer half life of six to eight days.
Now, production and secretion of thyroid hormones is under the control of the hypothalamus- pituitary axis. The hypothalamus, located at the base of the brain, secretes thyrotropin releasing hormone, or simply ΤRH, which stimulates the anterior pituitary cells called thyrotroph cells, to release the thyroid stimulating hormone, or TSH, into the bloodstream.
TSH then travels to the thyroid gland, and binds to the TSH receptors located in the membrane of the follicular cells of the thyroid gland.
When TSH binds to the TSH receptor, it goes on to promotes every aspect of T3 and T4 production, ranging from the iodide trapping to the release of thyroid hormones into the bloodstream.
Once released from the thyroid gland, T3 and T4 enter the circulation and travel via the blood by binding with the thyroxine binding globulin, or TBG, to reach the target cells.
Now, once inside the cell, T4 is mostly converted into T3 by the enzyme 5’- deiodinase. T3 binds to thyroid hormone receptors which are within the cell’s nucleus, and these receptors regulate gene expression, which ultimately lead to various metabolic and physiologic effects in the body.
For example, T3 speeds up the cell’s basal metabolic rate, especially when we have to adapt to the environment. So as an example, exposure to cold weather stimulates the release T3 and T4, and they go on to increase body metabolism and heat production by burning up more energy in the form of sugars and fats.
Thyroid hormones help activate the sympathetic nervous system, which is responsible for the fight or flight response. This increases heart rate which in turn increases the cardiac output, respiratory rate, and mental alertness.
Thyroid hormones also increase the gastrointestinal motility and they also have a very important growth and developmental role, and are necessary for normal neuronal development in growing fetuses and young children.

Primary hypothyroidism4:48–5:43

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.
Iodine deficiency can be a cause of primary hypothyroidism because the follicular cells don’t have the iodide ions they need to produce T3 and T4.
In countries that do fortify food with iodide, 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 and cause follicular cell damage and inhibit normal thyroid function.

Secondary hypothyroidism5:43–6:29

Primary hypothyroidism can also happen after treatment for hyperthyroidism, which usually involve surgically removing the thyroid gland, or destroying it with radioiodine therapy.
Now in secondary hypothyroidism, also called central hypothyroidism, the issue is that the body doesn’t produce enough TSH.
TSH is a really important hormone which stimulates thyroid gland to uptake iodide from the circulation and produce T3 and T4 when needed.
It typically happens because there’s a tumor in the anterior pituitary which compresses the gland and prevents TSH production, which leads to decreased level of T3 and T4,.

Congenital hypothyroidism6:29–6:51

So, the main problem with hypothyroidism is that it can happen in a few different ways but all of them result in a decrease of T3 and T4.
A person with low thyroid hormone levels typically have cold, dry skin, cold intolerance, hair loss, weight gain, and constipation.
They might also suffer mental symptoms like lethargy and fatigue. In infants and children, hypothyroidism could delay physical and mental development.

Symptoms6:51–7:41

Now, in some elderly individuals with low levels of thyroid hormones, any stressful event like an infection or a heart attack can lead to an acute decrease in T3 and T4.
This leads to an medical emergency known as myxedema coma, with symptoms like a sudden drop in body temperature, low heart rate, low blood pressure, confusion, and coma.
Okay, now in a person with hypothyroidism we want to increase the T3 and T4 to normal levels, and we can do it in two ways, first we can increase the production of thyroid hormone, or we can replace the missing hormones with thyroid hormone analogues.

Treatment7:41–8:26

If the hypothyroidism is due to iodine deficiency, the treatment is to give foods rich in iodine like fish, egg, meat and iodized salt.
If the problem is caused by damage to the thyroid gland or the pituitary gland that regulates it, the treatment of choice is to give synthetic thyroid hormone replacements, or thyroid hormone replacement therapy.
Now, the synthetic hormone that’s similar to T3 is called liothyronine, and the one that’s similar to T4 is called levothyroxine.
Both liothyronine and levothyroxine are usually given peroral but can also be given via the intravenous route. Another medication is porcine-derived dessicated thyroid which contains a mix of natural T3 and T4 hormones derived from pigs.

Liothyronine8:26–9:08

However, it’s not as reliable as the synthetic hormones since the amount of T3 and T4 in each dose could vary, which leads to unpredictability in its potency and duration.
Of the two synthetic thyroid hormones, Liothyronine is shorter acting, but much more potent - meaning it’s able to treat the symptoms of hypothyroidism at a lower dose.
Since it’s a T3 analogue, it could directly enter the target cell and take effect very rapidly. This is why intravenous liothyronine is the drug of choice in emergencies like myxoedema coma.
It’s high potency also leads to more severe side effects, which are the same as hyperthyroidism. This includes heat intolerance, anxiety, diarrhea, vomiting, tremors, and tachycardia which may lead to cardiac arrhythmias.

Levothyroxine9:08–12:35

That’s why liothyronine is contraindicated in individuals with heart conditions. Levothyroxine is much less potent but longer acting.
Just like natural T4, when it reaches the target cells, it first needs to be converted to T3 by the enzyme 5’- deiodinase.
Due to this, levothyroxine takes effect much slower than liothyronine, and individuals may require 6 to 8 weeks of therapy to achieve a normal T3 and T4 level.
On the other hand, the hyperthyroidism side effects are less severe and it’s the medication of choice for long term management of hypothyroidism and during pregnancy.
It is also not recommended for individuals with a history of heart diseases. All right, as a quick recap… When treating hypothyroidism, iodine deficiency can be treated by giving foods rich in iodine.
If the cause is thyroid or pituitary damage, synthetic or non- synthetic thyroid hormone replacement therapy could be used.
Liothyronine and levothyroxine are synthetic forms of T3 and T4. Levothyroxine is the drug of choice for treating chronic hypothyroidism, while liothyronine is used for myxoedema coma.
Non- synthetic thyroid hormones replacement uses porcine- derived dessicated thyroid is a mix of natural T3 and T4 derived from pigs but its effects are much less reliable when compared to synthetic thyroid hormones.

TSH suppressive therapy12:35–13:18

Side effects13:18–13:42

Contraindications13:42–14:20

Other preparations14:20–14:59

Review14:59–10:50