Thyrotoxic periodic paralysis
Thyrotoxic periodic paralysis | |
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thyroxine (thyroid hormone). | |
Specialty | Endocrinology |
Thyrotoxic periodic paralysis (TPP) is a rare condition featuring attacks of muscle weakness in the presence of hyperthyroidism (overactivity of the thyroid gland). Hypokalemia (a decreased potassium level in the blood) is usually present during attacks. The condition may be life-threatening if weakness of the breathing muscles leads to respiratory failure, or if the low potassium levels lead to abnormal heart rhythms.[1][2] If untreated, it is typically recurrent in nature.[1]
The condition has been linked with
Treatment of the low levels of potassium in the blood, followed by correction of the hyperthyroidism, leads to complete resolution of the attacks. It occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent.[1] TPP is one of several conditions that can cause periodic paralysis.[4]
Signs and symptoms
An attack often begins with muscle pain, cramping, and stiffness.
Attacks may be brought on by
There may be symptoms of thyroid overactivity, such as weight loss, a fast or irregular heart rate, tremor, and perspiration;[1][2] but such symptoms occur in only half of all cases.[5] The most common type of hyperthyroidism, Graves' disease, may additionally cause eye problems (Graves' ophthalmopathy) and skin changes of the legs (pretibial myxedema).[6] Thyroid disease may also cause muscle weakness in the form of thyrotoxic myopathy, but this is constant rather than episodic.[5]
Causes
Genetics
Genetic mutations in the L-type calcium channel α1-subunit (Cav1.1) have been described in Southern Chinese with TPP. The mutations are located in a different part of the gene from those described in the related condition
Of people with TPP, 33% from various populations were demonstrated to have mutations in KCNJ18, the gene coding for Kir2.6, an
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.[1]
Thyroid disease
The most common underlying form of thyroid disease associated with TPP is Graves' disease, a syndrome due to an
Mechanism
The muscle weakness and increased risk of irregular heart beat in TPP result from markedly reduced levels of potassium in the bloodstream. Potassium is not in fact lost from the body, but increased
It is not clear how the described genetic defects increase the Na+/K+-ATPase activity, but it is suspected that the enzyme becomes more active due to increased thyroid hormone levels. Hyperthyroidism increases the levels of catecholamines (such as adrenaline) in the blood, increasing Na+/K+-ATPase activity.[5] The enzyme activity is then increased further by the precipitating causes. For instance, increased carbohydrate intake leads to increased insulin levels; this is known to activate Na+/K+-ATPase. Once the precipitant is removed, the enzyme activity returns to normal levels.[1] It has been postulated that male hormones increase Na+/K+-ATPase activity, and that this explains why males are at a higher risk of TPP despite thyroid disease being more common in females.[2]
TPP is regarded as a model for related conditions, known as "channelopathies", which have been linked with mutations in ion channels; the majority of these conditions occurs episodically.[3]
Diagnosis
Hypokalemia (low blood potassium levels) commonly occurs during attacks; levels below 3.0 mmol/L are typically encountered. Magnesium and phosphate levels are often found to be decreased. Creatine kinase levels are elevated in two thirds of cases, usually due to a degree of muscle injury; severe elevations suggestive of rhabdomyolysis (muscle tissue destruction) are rare.[1][2] Electrocardiography (ECG/EKG) may show tachycardia (a fast heart rate) due to the thyroid disease, abnormalities due to cardiac arrhythmia (atrial fibrillation, ventricular tachycardia), and conduction changes associated with hypokalemia (U waves, QRS widening, QT prolongation, and T wave flattening).[2] Electromyography shows changes similar to those encountered in myopathies (muscle diseases), with a reduced amplitude of the compound muscle action potentials (CMAPs);[4] they resolve when treatment has commenced.[1]
TPP is distinguished from other forms of periodic paralysis (especially
Treatment
In the acute phase of an attack, administration of potassium will quickly restore muscle strength and prevent complications. However, caution is advised as the total amount of potassium in the body is not decreased, and it is possible for potassium levels to overshoot ("rebound hyperkalemia"); slow infusions of potassium chloride are therefore recommended while other treatment is commenced.[1]
The effects of excess thyroid hormone typically respond to the administration of a non-selective beta blocker, such as propranolol (as most of the symptoms are driven by increased levels of adrenaline and its effect on the β-adrenergic receptors). Subsequent attacks may be prevented by avoiding known precipitants, such as high salt or carbohydrate intake, until the thyroid disease has been adequately treated.[1]
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
Epidemiology
TPP occurs predominantly in males of Chinese, Japanese, Vietnamese, Filipino, and Korean descent,[1] as well as Thais,[3] with much lower rates in people of other ethnicities.[1] 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%.[1][2] Native Americans, who share a genetic background with East Asians, are at an increased risk.[1]
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.[1][2]
History
After several case reports in the 18th and 19th centuries, periodic paralysis was first described in full by the German neurologist Karl Friedrich Otto Westphal (1833–1890) in 1885.[7][8] In 1926 the Japanese physician Tetsushiro Shinosaki, from Fukuoka, observed the high rate of thyroid disease in Japanese people with periodic paralysis.[9][10] 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.[2][10] In 1937 periodic paralysis was linked with hypokalemia, as well as precipitation of attacks with glucose and insulin.[11][12] This phenomenon has been used as a diagnostic test.[12]
In 1974 it was discovered that propranolol could prevent attacks.[13] The concept of channelopathies and the link with specific ion channel mutations emerged at the end of the 20th century.[1][3][4]
References
- ^ PMID 16608889.
- ^ S2CID 24394963.
- ^ S2CID 16230992.
- ^ PMID 19185183.
- ^ PMID 15667036.
- ^ PMID 11071676.
- ^ Westphal CF (1885). "Über einen merkwürdigen Fall von periodischer Lähmung aller vier Extremitäten mit gleichzeitigem Erlöschen der elektrischen Erregbarkeit während der Lähmung". Berl. Klin. Wochenschr. (in German). 22: 489–91 and 509–11.
- PMID 20301512.
- S2CID 76554730.
- ^ .
- ^ Aitken RS, Allott EN, Castleden LI, Walker M (1937). "Observations on a case of familial periodic paralysis". Clin. Sci. 3: 47–57.
- ^ PMID 6017520.
- PMID 4432863.
External links