Thyrotoxic Periodic Paralysis (TPP) is a condition characterized by intermittent episodes of muscle weakness or paralysis occurring in people with hyperthyroidism. Muscles of the arms and legs are most commonly affected. Other affected muscles include muscles of the eye, muscles involved in breathing and swallowing, and cardiac muscles, which may sometimes lead to vision changes, difficulty in breathing, swallowing, and speaking. The attacks are characterized by low levels of serum potassium levels. The paralytic episodes are usually triggered by hyperinsulinemia, carbohydrate overload, high salt intake, and/or vigorous exercise, and usually last from a few hours to several days. It is presumed that the thyroid hormone stimulates the Na+-K+ ATPase dependent K+ channel, resulting in the pathophysiology of the disease. TPP is the most common secondary hypokalemic periodic form of paralysis, and is more common in Asian and Hispanic individuals. Among Chinese, the prevalence of TPP is estimated to be 13-14%. The disease is not so common among Caucasians. In addition, TPP affects predominantly males.
A diagnosis of TPP is confirmed if intermittent paralytic episodes are supported by abnormally low levels of serum thyroid stimulating hormone, and high levels of thyroid hormone. During the attacks, ECG may show abnormalities, although the EMG will be normal, and the serum potassium level will be low. Treatment during an attack will involve immediate administration of potassium, and ensure rapid reduction in thyroid levels. Occasionally, patients may not respond to potassium administration, in which case intravenous propranolol is administered. Beta blockers are also indicated to reduce the severity of the attacks.
A recent study has described a mutation in the KCNE3 gene to be responsible for the TPP phenotype. The mutant was shown to decrease the outward potassium flux, resulting in a more positive membrane potential. HLA subtype differences with relation to TPP amongst different races have also been studied, among Japanese (DRw8), Singapore Chinese (A2BW22, AW19B17), and Hong Kong Chinese (B5, BW46). Apart from the KCNE3 gene, other polymorphisms have also been reported in CACNA1S, SCN4A, KCNE1, KCNE2, KCNE1L, KCNJ2, KCNJ8, and KCNJ11 genes.