Periodic Paralysis
June  2014

​​​​​A 29 year-old man applied for life insurance. Two-and-a-half years prior to the application he reported an episode of lower extremity weakness and inability to walk which resolved over a period of several days. He lost 40 pounds, and did well until 10 months prior to application.

At that time he again developed weakness and was taken to the emergency room. His serum potassium was found to be 2.1 (3.5-5.5 mEq/L). He was given potassium supplements and discharged.

Two months later he had another episode of weakness and “collapse” and was diagnosed with thyrotoxicosis and periodic paralysis. His serum potassium level was normal at that time.

He had another episode of “shakes, palpitations, fatigue and heat intolerance” about a month later. The last records from two months prior to application showed he was prescribed a potassium supplement and had a normal serum potassium, a TSH of .01 (0.4-4.5 mIU/L) and a T4 of 0.8 (0.8-1.8 mg/dl).

What are the mortality implications of the diagnosis?

Periodic paralyses (PP) are a heterogeneous group of disorders, of which thyrotoxic periodic paralysis is a specific entity. Typically, they present as irregular episodes of flaccid muscle weakness, and most are associated with alterations in serum potassium levels. Many are inherited either as an autosomal dominant pattern with variable penetrance or as a sporadic point mutation.

They can also be categorized as hypokalemic, hyperkalemic and paramyotonic forms. In general, these genetic alterations affect the ion channels in the cell membranes of muscle cells. The ion channels move potassium and other ions into or out of cells, and the defective channels cause the muscle cells to become depolarized and unable to contract. Cranial musculature and respiratory muscles are often spared. One form of periodic paralysis, Anderson-Tawil Syndrome, is also associated with prolonged QT syndrome and significant arrhythmias of the heart, fainting and sudden death.

Thyrotoxic periodic paralysis (TPP) is the most common type of secondary, hypokalemic PP. 85 percent of cases occur in males. TPP occurs most often in males of Chinese, Japanese, Vietnamese, Filipino, Korean or Thai descent, although it has been reported in 0.1-0.2% of those with hyperthyroidism in the US.

The typical age at onset is between 20 & 40. Triggering factors such as salt or carbohydrate loading, exercise, fatigue and hyperinsulinemia have been reported. An episode often begins with cramping, stiffness and muscle pain. The weakness is usually proximal and symmetric and typically starts in the legs and moves to the arms.

A flaccid paralysis and hypoactive reflexes are seen during attacks. The attacks last from hours to days and often resolve spontaneously. Often, low serum potassium is observed during episodes of weakness. Typically, strength returns to normal between episodes, but fixed muscle weakness may develop over time.

Changes of hypokalemia (QT prolongation, QRS widening, U waves and flattened T waves) can be seen on the electrocardiogram. Physical signs of thyrotoxicosis may also be observed: rapid pulse, perspiration, enlarged or tender thyroid, exophthalmos, etc. The combination of low serum potassium during an attack and low Thyroid Stimulating Hormone (TSH) combined with elevated thyroid hormone levels is sufficient to make the diagnosis of TPP.

Treatment of TPP consists of potassium supplementation during an episode (with caution as the total body potassium may be normal, and rebound hyperkalemia may occur as potassium moves out of cells). The symptoms of thyrotoxicosis can be controlled with beta-blockers. And this can be followed by definitive treatment of the hyperthyroidism with antithyroid drugs, surgery or radioactive iodine.

The treatment of the thyroid disease almost always results in the resolution of the episodes of paralysis.

Returning to the Case

Given the information above, there is slight mortality risk associated with TPP during the episode due to potential paralysis of respiratory muscles or arrhythmias related to hypokalemia. There was no indication in the current case that the thyroid disease was being treated. But after the thyroid disease is treated and stability is established, the extra mortality risk should be minimal.


Lin S. “Thyrotoxic Periodic Paralysis.” Mayo Clin Proc. 2005;80(1):99-105.
Hsu Y, et al. “Electrocardiographic Manifestations in Patients with Thyrotoxic Periodic Paralysis.” Am J Med Sci, 2003;326(3):128-132.