In TPP, the mutations described are single-nucleotide polymorphisms located in the hormone response element responsive to thyroid hormone, implying that transcription of the gene and production of ion channels may be altered by increased thyroid hormone levels. Furthermore, mutations have been reported in the genes coding for potassium voltage-gated channel, Shaw-related subfamily, member 4 (Kv3.4) and sodium channel protein type 4 subunit alpha (Na41.4).Of people with TPP, 33% from various populations were demonstrated to have mutations in KCNJ18, the gene coding for Kir2.6, an inward-rectifier potassium ion channel. This gene, too, harbors a thyroid response element.Certain forms of human leukocyte antigen (HLA)—especially B46, DR9, DQB1*0303, A2, Bw22, AW19, B17, and DRW8—are more common in TPP. Linkage to particular forms of HLA, which plays a central role in the immune response, might imply an immune system cause, but it is uncertain whether this directly causes TPP or whether it increases the susceptibility to Graves disease, a known autoimmune disease. Thyroid disease
The most common underlying form of thyroid disease associated with TPP is Graves disease, a syndrome due to an autoimmune reaction that leads to overproduction of thyroid hormone. TPP has also been described in people with other thyroid problems such as thyroiditis, toxic nodular goiter, toxic adenoma, TSH-producing pituitary adenoma, excessive ingestion of thyroxine or iodine, and amiodarone-induced hyperthyroidism. Mechanism
The muscle weakness and increased risk of irregular heart beat in TPP result from markedly reduced levels of potassium in the bloodstream.
Subsequent attacks may be prevented by avoiding known precipitants, such as high salt or carbohydrate intake, until the thyroid disease has been adequately treated.Treatment of the thyroid disease usually leads to resolution of the paralytic attacks. Depending on the nature of the disease, the treatment may consist of thyrostatics (drugs that reduce production of thyroid hormone), radioiodine, or occasionally thyroid surgery. Epidemiology
TPP occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent, as well as Thais, with much lower rates in people of other ethnicities. In Chinese and Japanese people with hyperthyroidism, 1.8–1.9% experience TPP. This is in contrast to North America, where studies report a rate of 0.1–0.2%. Native Americans, who share a genetic background with East Asians, are at an increased risk.The typical age of onset is 20–40. It is unknown why males are predominantly affected, with rates in males being 17- to 70-fold those in females, despite thyroid overactivity being much more common in women. History
After several case reports in the 18th and 19th centuries, periodic paralysis was first described in full by the German neurologist Carl Friedrich Otto Westphal (1833–1890) in 1885. In 1926 the Japanese physician Tetsushiro Shinosaki, from Fukuoka, observed the high rate of thyroid disease in Japanese people with periodic paralysis. The first English-language report, in 1931, originated from Dunlap and Kepler, physicians at the Mayo Clinic; they described the condition in a patient with features of Graves disease. In 1937 periodic paralysis was linked with hypokalemia, as well as precipitation of attacks with glucose and insulin.