Thyrotoxic (hypokalemic) Periodic Paralysis
When an overactive thyroid gland causes hypokalemic periodic paralysis, the result is a disorder called thyrotoxic periodic paralysis (TPP).
Periodic paralysis is a rare genetic disorder that is characterized by temporary attacks of extreme muscle weakness or paralysis. These attacks can be triggered by a variety of things, with the most common triggers being resting after exercise, cold temperatures, and having too much or too little potassium. There are several types of periodic paralysis. Understanding the different types can be difficult, but we are here to give you guidance.
Periodic paralysis is caused by muscle cells that do not have the right balance of chemicals to work properly. Muscle cells have openings called channels that open and close to let particles such as sodium, potassium, and calcium go in and out. These particles are called ions, and muscle cells can only work if the right kinds of ions enter and exit the cells at the right times. When the channels don’t open and close the way they’re supposed to, the ions become imbalanced, and muscles aren’t able to function normally.
Thyrotoxic periodic paralysis (TPP, THPP, or THKPP) is a variant of hypokalemic periodic paralysis. “Hypo” means that there is a low amount of something, and “kalemic” refers to potassium. Hypokalemic patients experience attacks that are triggered by low blood potassium levels, and potassium levels usually fall during attacks, too. The same is true for people with thyrotoxic periodic paralysis. The difference is that this disorder is caused by an overactive thyroid gland. One important fact to note is that this disorder disproportionately affects males of Asian descent.
Thyrotoxic periodic paralysis is caused by thyrotoxicosis, which is another word for hyperthyroidism. This means that a person’s thyroid gland is overactive. The thyroid gland is located at the base of your neck, and it produces hormones that affect many things in your body, including your heart rate, metabolism, and the composition of your blood. Conditions such as Grave’s disease can cause the thyroid gland to overproduce hormones, leading to symptoms like irregular heartbeat, night sweats, swollen eyes, brittle bones — and muscle weakness attacks.
These attacks may last from a few hours to a few days. The frequency of attacks can vary greatly between different people. Some people have attacks every day, others have them several times per month, while there are others who have them every few months or less often. The strength of the attacks isn’t always consistent — sometimes, the patient feels fatigued, but can still move around slowly. Other times, they aren’t able to move at all and they may seem like they are unconscious (even though they really are conscious). Attacks may affect one area, like an arm or leg, or many areas at once around the body. Lower limbs and extremities are most likely to be affected.
Attacks of thyrotoxic periodic paralysis can be triggered by the patient not having enough potassium in their blood (AKA serum potassium). High levels of insulin in the blood might also contribute to attacks. During attacks, patients’ blood often contains imbalanced amounts of chemicals like magnesium and creatine phosphokinase.
Thyrotoxic periodic paralysis attacks have several different triggers, and not every person has the exact same set of triggers. Eating high-carb foods or high-sodium foods might bring about an attack. Each person who has this disorder has to figure out over time which foods are triggers for them and which foods are not. Being cold is also a trigger, which presents major challenges for people living in cold climates.
Exercising and then resting afterward can trigger an attack, especially if the exercise was intense. Sleeping can be a trigger, because some people unknowingly have attacks while they are sleeping, and many have attacks as soon as they wake up. Stressful emotions tend to trigger attacks, too. It may be helpful to keep a trigger diary to record what time attacks happen, how you felt during the attacks, and what you were doing before attacks.
Thyrotoxic periodic paralysis can affect anyone, but it disproportionately affects Asian males. Patients often start to experience attacks between the ages of 20 and 40. They may also experience overactive thyroid symptoms, but in some cases, those symptoms are so mild that the patient doesn’t feel a need to visit a doctor for them. They will instead go to the doctor for muscle weakness attacks.
However, because periodic paralysis is a rare disorder that many doctors don’t know about, it’s likely for doctors to misdiagnose the patient, giving them an incorrect reason why they are having muscle weakness attacks. It often takes years for periodic paralysis suffers to be given the correct diagnosis of periodic paralysis.
Giving doctors your family’s health history and your trigger diary can help them come closer to a periodic paralysis diagnosis, and there are other diagnostic tools available, too. A muscle biopsy is sometimes needed for doctors to diagnose periodic paralysis. This means that the doctor must remove and examine a small piece of the patient’s muscle tissue during or after an attack to see if the muscle tissue is abnormal. Another diagnosis method is the Compound Muscle Action Potential test, which measures the electrical activity of muscles. This test can’t always detect periodic paralysis, but it can do so in a lot of cases. Genetic testing is a method that has been used sometimes to diagnose some types of periodic paralysis, but when it comes to thyrotoxic periodic paralysis, it is not known for sure whether or not there is a genetic link. Some research has suggested that there is.
Measuring a patient’s potassium levels before, during, and after attacks can help a doctor determine whether or not the patient is hypokalemic. If the patient is hypokalemic, the doctor should perform a blood test to find out if the thyroid is overactive in the amount of hormones it is putting into the blood. If so, the doctor will be able to diagnose thyrotoxic periodic paralysis.
During a thyrotoxic periodic paralysis attack, the patient’s blood potassium levels fall to an abnormally low level. For this reason, potassium chloride (KCl) can be given orally to the patient as a treatment. Sometimes, the beta-blocker drug propranolol is also given to the patient. Beta-blockers are drugs used to treat heart irregularities, so these drugs can help patients with an overactive thyroid gland that causes heart irregularities.
The good news about thyrotoxic periodic paralysis is that it is the only type of periodic paralysis that can be cured! Once the thyroid gland has been fully treated and goes back to normal (euthyroid), the periodic paralysis attacks will no longer happen. Drugs that can treat an overactive thyroid include methimazole, propylthiouracil, and radioiodine. (One medication to avoid is acetazolamide, which can be helpful for people with hypokalemic periodic paralysis but can actually make thyrotoxic periodic paralysis attacks worse!)
Getting the thyroid gland back to normal might take months or even years, so it’s important for people with thyrotoxic periodic paralysis to live a lifestyle that minimizes triggers. Staying in warm environments, keeping stress under control, eating a low-sodium and low-carb diet, and avoiding strenuous exercise can reduce the likelihood of an attack happening. Potassium supplements might reduce attacks as well. Regularly taking beta-blockers like propranolol can be a way to lessen the severity of attacks during this time period when the thyroid gland is in the process of returning to normal.
Your Next Steps
If you think you may have thyrotoxic periodic paralysis, please talk with your doctor. Speaking with a doctor about a rare disorder can be intimidating, and many doctors have little to no prior knowledge about periodic paralysis. The PPA has many resources to help you become a better advocate for yourself. Click here to learn about other types of periodic paralysis. You can also submit a question to our Ask the Experts panel. Remember, we are here to support you all the way as you take action to advocate for your health!
Disease and Diagnostic Criteria
Unfortunately, we do not understand why or how elevated thyroid function tests and thyroid hormone induce attacks in susceptible individuals.
Regarding medications, beta blockers have been found to control the condition. Acetazolamide generally makes attacks more frequent and more severe in thyrotoxic periodic paralysis (but generally makes attacks less frequent and less severe in familial hypokalemic periodic paralysis). Achieving a euthyroid state also reverses the condition. If the patient is on propylthiouracil or methimazole, then stopping these antithyroid medications will result in a hyperthyroid state. When this occurs, symptoms of periodic paralysis recur.
Any thyroid condition that causes hyperthyroidism can induce periodic paralysis in susceptible individuals. Please be certain that the cause of the hyperthyroidism is found (i.e. Grave’s disease vs. carcinoma, etc.).
A nice review on thyrotoxic periodic paralysis can be found in:
Ober, K. Patrick, “Thyrotoxic Periodic Paralysis in the United States Report of 7 Cases and Revie of the Literature.” Medicine, (1992); 71(3):109-120.
The primary cause of thyrotoxic periodic paralysis is unknown. In terms of management, the same triggers that cause attacks for familial hypokalemic periodic paralysis cause attacks for thyrotoxic periodic paralysis.
Levitt J. Management of Periodic Paralysis. J Translational Medicine.