Abstract

Epidemiology Thyrotoxic periodic paralysis (TPP) is most common in Asian males (with male-to-female ratios ranging from 17:1 to 70:1) during the third decade of life: the annual incidence in Chinese and Japanese thyrotoxicosis patients is estimated at around 1/50, whereas it is estimated at 1-2/1,000 among non-Asian thyrotoxicosis patients.Clinical description TPP manifests as recurrent episodes of acute flaccid muscular weakness predominantly involving proximal muscles, with a greater involvement of the lower limbs than the upper limbs. The severity of attacks ranges from mild paresis to complete paralysis. Recovery occurs within 2-72 hours. Attacks typically occur at night and may be preceded by muscle cramps, aches and stiffness. Ocular, bulbar and respiratory involvement has also been reported but is rare. Attacks are triggered by the ingestion of a high-carbohydrate load or strenuous physical activity followed by a period of rest. Episodes only occur when patients are thyrotoxic, but symptoms and classical signs of hyperthyroidism are often absent at the time of the first attack. TPP can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves' disease.Etiology The pathogenesis remains unclear. Genetic predisposition is thought to play a role in the pathogenesis of TPP, and loss-of-function mutations in KCNJ18 (17 p11), single-nucleotide polymorphisms (SNPs) of the CACNA1S (1q32) and GABRA3 (Xq28) genes have been associated with TPP susceptibility in some Asian populations. Hypokalemia is the consequence of an extra- to intracellular potassium shift due to an increase in Na/K-ATPase pump activity, either as a direct response to thyroid hormone or indirectly via adrenergic stimulation, insulin or exercise.Diagnostic methods The diagnosis of TPP is considered in the setting of hypokalemic paralysis and thyrotoxicosis in the absence of other causes for hypokalemia. Other anomalies may include hypophosphatemia and hypomagnesemia, without changes in acid-base balance. EMG reveals myopathic changes during attacks and muscle excitability anomalies after a prolonged exercise test. ECG changes of hypokalemia may be noted. Absence of family history, age of onset (20 to 40 years), and thyrotoxicosis help distinguish TPP from familial hypokalemic periodic paralysis (FHPP), and low urine potassium helps differentiate it from renal potassium-wasting disorders.Differential diagnosis The differential diagnosis may include Guillain-Barré syndrome, transverse myelitis, spinal cord compression and myasthenia gravis, as well as muscle weakness due to familial hypokalemic periodic paralysis (FHPP) and hypokalemia due to renal or gastrointestinal loss.Genetic counseling Genetic counseling is not required. Thyrotoxic periodic paralysis is sporadic and an acquired disorder.Management and treatment Management of TPP includes definitive control of hyperthyroidism, prevention of attacks with beta adrenergic blockers, and avoidance of precipitating factors, such as a high carbohydrate diet. Potassium replacement is the mainstay of treatment during acute episodes to hasten the recovery from paralysis and to prevent cardiac arrhythmias. Intravenous potassium replacement needs close monitoring to avoid rebound hyperkalemia.Prognosis Acute episodes can be life-threatening due to cardiac arrhythmia and respiratory failure, but death rarely occurs. The prognosis for patients is good, and TPP resolves when euthyroid status is achieved.