Hyperthyroidism medications

Definitions & Key takeaways

Hyperthyroidism refers to a condition in which there is excess thyroid hormones. Medications used to treat hyperthyroidism aim at reducing the level of thyroid hormones or the management of associated symptoms. Hyperthyroidism medications include beta blockers, radioactive iodine, propylthiouracil, methimazole, Lugol's iodine, propranolol, and corticosteroids.

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Introduction0:00–0:24

In hyperthyroidism, ‘hyper’ refers to having too much, and ‘thyroid’ refers to thyroid hormones, so hyperthyroidism refers to a condition where there’s excess thyroid hormones.
Medications used to treat hyperthyroidism either reduce the level of thyroid hormones or treat the symptoms by targeting the affected tissue.
There are 2 different thyroid hormones; triiodothyronine or T3, and thyroxine or T4. 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.

Physiology0:24–3:45

Zooming further into these follicular cells, we’ll see their 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.
Synthesis of thyroid hormones begins when follicular cells take in inorganic iodide ions from the blood, along with two sodium ions, via a sodium- iodide symporter.
This step is known as ‘iodide trap’. The iodide ion is pumped via the pendrin protein, into the viscous fluid inside the follicle called the colloid, which contains thyroglobulin; the precursor of thyroid hormone.
In the colloid, inorganic iodide undergoes oxidation via the enzyme thyroid peroxidase or TPO, to become organic iodide, which then binds to the tyrosine in thyroglobulin.
This step is known as iodination. Some tyrosine residues bind to only one iodine and form monoiodotyrosine or MIT, whereas others bind to two iodine atoms to form diiodotyrosine or DIT.
These molecules are then coupled together by the same enzyme thyroid peroxidase. This process is known as coupling.
Coupling one MIT with one DIT create T3, while coupling 2 DIT molecules create T4. T4 is generally created in greater amounts than T3, with T3 being the more active form with a half life of 1 to 2 days, while T4 is less active but has a longer half life of 6 to 8 days.
Once released from the thyroid gland, T3 and T4 enter the circulation, travels through the blood bound to thyroxine - binding globulin, and enter the target cell.
Inside the cell, T4 is converted into T3 by the enzyme 5’- deiodinase. T3 binds to thyroid hormone receptors in the cell’s nucleus which ultimately lead to increased cellular activity.
This increase in metabolism uses up sugars and fats for energy and produce more body heat. Thyroid hormones also help activate the sympathetic nervous system which is responsible for the fight or flight response.
This increases heart rate and cardiac output, respiratory rate, and mental alertness. Thyroid hormones also increase the gastrointestinal or gi motility and they are necessary for normal neuronal development in growing fetuses and young children.
Now, hyperthyroidism can happen in a few different ways. The most common cause is Graves disease, an autoimmune disorder where B cells produce antibodies against thyroid stimulating hormone receptors on follicular cells.
These antibodies bind to the receptors and activate them, which causes the thyroid follicles to grow and produce more thyroid hormones.
One complication is Graves ophthalmopathy which is inflammation and edema in the tissue around the eyes, causing the eyelids to retract and giving the eyes a “bulging” appearance.
Other disorders like toxic multinodular goiter and thyroiditis can also cause increased release of thyroid hormones. Now, the symptoms of hyperthyroidism include 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 or tachycardia, sweating, hyperactivity, anxiety and insomnia because of the effect of thyroid hormones on the sympathetic nervous system.

Pathology3:45–5:41

Untreated hyperthyroidism combined with a stressor like an infection or illness can trigger a life- threatening complication called thyroid storm.
Many of the symptoms of hyperthyroidism then become exaggerated, leading to severe tachyarrhythmia, high fever, delirium, and coma.
Now, there are several classes of medications to control hyperthyroidism. First, we can target the thyroid gland itself, and either decrease the synthesis of thyroid hormones or prevent them from being released.
The other option, at the target tissue peripherally; is to decrease the effectiveness of the thyroid hormones; this only manages the symptoms but doesn’t treat the cause.
Let’s start with the radioactive iodine therapy, also known as “radioiodine ablation therapy”. The isotope of iodine that is used is I131 .
It’s taken peroral and eventually gets taken up by the thyroid. Over the course of a few weeks, the radioactive isotope collects in the colloid and emits radiation that causes permanent damage of the thyroid.
This is the definitive treatment for hyperthyroidism caused by Graves disease and toxic multinodular goiter, but it could also worsen Graves ophthalmopathy.
Radioactive iodine crosses the placenta and is secreted in breast milk, so it should be avoided in people who are pregnant or breastfeeding.
Since the thyroid is permanently destroyed, the person will need to take thyroid hormone replacements like levothyroxine to prevent hypothyroidism.

Radioactive iodine therapy5:41–6:55

Now, since radioactive iodine is contraindicated in pregnancy, and can take weeks to take effect, we can use thioamides like propylthiouracil, or PTU, and methimazole to decrease the production of thyroid hormones.
Both of these medications are given perorally and are absorbed by the thyroid where they inhibit thyroid peroxidase. This stops the oxidation of iodide ions into organic iodine, and the coupling of MIT and DIT to form T3 and T4.
In addition, PTU also works in the peripheral tissue by inhibiting 5’- deiodinase to block the conversion of T4 into T3, which makes it the preferred medication during thyroid storms.
The main side effects of these medications include hypothyroidism, lupus like syndrome, and agranulocytosis. Agranulocytosis is the most dangerous side effect, since the decrease in neutrophils can make a person more susceptible to infections.
Both propylthiouracil and methimazole also worsen Graves ophthalmopathy. PTU’s drug specific side effect is hepatotoxic and could cause liver failure, so methimazole is usually the preferred medication.

Thioamides6:55–9:19

Both methimazole and PTU can cross the placenta and cause hypothyroidism in the fetus. Because of this, PTU is the better medication during the first trimester since methimazole could cause congenital defects when the fetus is vulnerable.
During the 2nd and 3rd trimesters, after the risk period is over, methimazole is the preferred medication. Moving on!
Although iodine is needed for the synthesis of thyroid hormones, in higher concentrations it actually inhibits the release of T3 and T4 into the circulation.
Lugol’s iodine solution can be used to treat hyperthyroidism, but it’s not consistent since the thyroid could adapt and resumes hormone synthesis after the initial few weeks.
High levels of iodine also cause decreased blood flow to the thyroid, so it’s commonly used a few days before thyroid surgery to reduce the risk of severe bleeding.
Finally, beta blockers like propranolol are used to block beta receptors in tissue innervated by the sympathetic nervous system.
This could reduce sympathetic symptoms of hyperthyroidism like rapid heart rate, sweating, hyperactivity, anxiety and tremors.
In addition, propranolol decreases the conversion of T4 into T3 just like PTU, and could be used during thyroid storms. Next, glucocorticoids like prednisone can decrease the inflammation around the eyes and are used to reduce Graves ophthalmopathy before radioactive iodine could be given.
We want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these crazy pharmacology facts!
So let’s put all the medications that act on the thyroid inside a room and all the medications that acts peripherally outside in the yard.
First, in the room, there’s a giant bottle of iodine with a radiation hazard sign on it for radioactive iodine. The radiation is setting the nearby wall on fire to help you remember it destroys the thyroid.
In the middle of the room is a pair of oxygen tanks to represent thyroid peroxidase, and we can put the thioamides here.
The oxygen is for a nasty old farmer who’s spitting out the window going “ptooey” for PTU. He’s spitting on the 5 year old kid outside who’s smashing iodine bottles since PTU also inhibits 5’- deiodinase.
The farmer grows giant maize, or corn, with numbers on the kernels for methimazole. For the side effects of these 2 medications, let’s put a pile of grains on the floor to represent agranulocytosis, and also a wolf, for lupus like syndrome.

Iodide salts & iodine9:19–11:12

The farmer is also carrying a plate of liver to represent PTU’s hepatotoxicity. PTU is a jerk so he’s not the preferred medication.
On the other hand, he’s a surprisingly good dad so he’s carrying a fetus because PTU is used during the 1st trimester. 2 more older babies are climbing on the giant corn because it can be used during the 2nd and 3rd trimesters.
For Lugol’s iodine, let’s have a large stack of iodine bottles blocking the door to the outside since high concentrations of iodine blocks thyroid hormone release.
The stack is also crushing a red hose to help you remember it causes decreased blood supply to the thyroid. Moving outside, we can see the medications that act peripherally.
Let’s put a propane grill with a laughing face on it for propranolol, next to the kid with the hammer since it also inhibits 5’- deiodinase.
There’s a Bee cooking on the grill to help you remember it’s a Beta blocker that treats sympathetic symptoms. Finally, there’s also a buff courtroom judge to represent corticosteroids.
He’s banging his gavel on a gravestone with googly eyes attached to it to help you remember it’s used to treat Graves ophthalmopathy.
All right, as a quick recap... Treatment for hyperthyroidism include medications that target the thyroid and those that target peripheral tissues.
Radioactive iodine offers a permanent solution for hyperthyroidism since it destroys the thyroid gland. PTU and methimazole prevents thyroid hormone synthesis and PTU also prevents conversion of T4 into T3 peripherally.
Lugol’s iodine prevents the release of thyroid hormones and can decrease the blood flow to the thyroid. In the peripheral tissue, propranolol reduce the sympathetic symptoms of hyperthyroidism and decrease the conversion of T4 into T3.

Beta-blockers & glucocorticoids11:12–11:55

And lastly, corticosteroids are used to treat Graves ophthalmopathy. But wait, there's more: Here's a mind map with all of the mnemonics from the video.
Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers at the end.

Memory palace11:55–14:10

Review14:10–14:56

Mind map14:56–11:34