Medline ® Abstracts for References 2-7

Although hypokalemic periodic paralysis is a common complication of hyperthyroidism among Asian populations, it is an uncommon problem in the United States. The recent experience in an American medical center with 7 patients with thyrotoxic periodic paralysis (TPP) is reviewed. Compared to most descriptions of this disorder, which tend to reflect the international experience with this disease, patients with TPP in the United States reflect the ethnic makeup of the local population: the predisposition of patients of Asian origin is very evident, but whites are more frequently affected than most previous reports have recognized. Hispanics and American Indians also appear to be at increased risk, and blacks have also been affected. Except for the fact that hyperthyroidism is an absolute requirement for expression of the disease, TPP is identical to familial periodic paralysis (FPP) in its clinical presentation. TPP affects predominantly males (to an even greater degree than FPP), is rarely associated with a positive family history, and has a later onset of presentation than FPP (reflecting the need for hyperthyroidism to occur before the disorder can be expressed). Graves disease is the most common cause of hyperthyroidism in affected patients, but any cause of thyrotoxicosis (including administration of excessive amounts of exogenous thyroid hormone) can trigger attacks of TPP in susceptible subjects. Clinical features of thyroid disease may be very subtle or virtually nonexistent; as a result, thyroid function tests should be routinely monitored in patients with features of hypokalemic paralysis. The pathophysiology of the disorder is not well understood. Definitive treatment of hyperthyroidism leads to cessation of periodic hypokalemic paralysis, but symptoms can return with recurrence of the hyperthyroid condition. Potassium administration during an acute attack will shorten the duration of the episode, and treatment with propranolol, potassium supplementation, or spironolactone may prevent attacks in some patients.

OBJECTIVE: To examine whether sodium pump activity plays a part in the pathogenesis of thyrotoxic periodic paralysis.

DESIGN: Measurement of platelet sodium-potassium ATPase and in vivo sodium pump activities in healthy subjects and thyrotoxic subjects with and without paralysis.

SETTING: University hospital in Hong Kong.

SUBJECTS: 21 healthy subjects, 23 untreated thyrotoxic subjects, 13 untreated men with periodic paralysis, seven treated thyrotoxic subjects, and six treated men with periodic paralysis.

MAIN OUTCOME MEASURES: Platelet Na+, K(+)-ATPase activity and plasma rubidium concentration after oral loading.

RESULTS: Median (range) platelet Na+, K(+)-ATPase activity in thyrotoxic subjects was 253 (169-821) mumol inorganic phosphate/h/g protein--significantly higher than that in healthy subjects (134 (81-180) mumol/h/g protein; p less than 0.001). Na+, K(+)-ATPase activity in those with periodic paralysis was 374 (195-1196) mumol/h/g protein, again significantly higher than that in healthy subjects (p less than 0.001) and that in other thyrotoxic subjects (p less than 0.01) despite similar degrees of hyperthyroidism. Activities in treated thyrotoxic subjects with and without periodic paralysis were 148 (110-234) and 131 (86-173) mumol/h/g protein respectively. Mean (95% confidence interval) plasma rubidium concentration five hours after oral administration in thyrotoxic subjects (7.0 (6.6 to 7.5) mumol/l) was significantly lower than in healthy subjects (10.2 (9.5 to 10.9) mumol/l; p less than 0.001) and higher than in those with periodic paralysis (6.0 (5.7 to 6.3) mumol/l; p less than 0.01).

CONCLUSIONS: Sodium pump activity in untreated subjects with periodic paralysis is higher than in other thyrotoxic subjects, and this may be responsible for the hypokalaemia.

We retrospectively evaluated the characteristics of adult patients admitted with thyrotoxic hypokalaemic periodic paralysis in Hong Kong. From 1984 to 1993, 45 Chinese adult patients were admitted with acute limb weakness, plasma potassium<or = 3.5 mmol/l and thyrotoxicosis confirmed by laboratory investigations. All but one were male. Seventy-five percent of attacks occurred between 9pm and 9am. Half of the attacks occurred between July and October (49.1%), most commonly in August (20%). Mean (+/- SEM) plasma potassium on admission was 2.17 +/- 0.08 mmol/l (range 1.1-3.5). In 15 episodes (27.3%), plasma potassium on recovery exceeded 5.0 mmol/l, while in three episodes (5.5%), potassium exceeded 6.0 mmol/l. No patient had a positive family history of thyrotoxic periodic paralysis. Only 28.9% had a known history of thyrotoxicosis before their first presentation with periodic paralysis. Twenty-seven (60%) had clinical evidence of thyrotoxicosis. Although all were biochemically thyrotoxic, 11.4% had only a mild degree of thyrotoxicosis (suppressed thyroid-stimulating hormone, high free thyroxine, but normal free triiodothyronine). One quarter of the patients had a normal erythrocyte zinc concentration, indicating either a short history of thyrotoxicosis or transient thyrotoxicosis. The diagnosis of thyrotoxic hypokalaemic paralysis should always be considered in Chinese patients with acute muscle weakness, especially in young males. Absence of clinical thyrotoxicosis doesnot exclude the diagnosis. Plasma potassium should be monitored carefully during treatment to prevent rebound hyperkalaemia.

Thyrotoxic periodic paralysis (TPP), a hyperthyroidism-related hypokalemia and muscle-weakening condition resulting from a sudden shift of potassium into cells, has been seen increasingly in Western countries. Failure to recognize TPP may lead to improper management. Many patients with TPP have no obvious symptoms related to hyperthyroidism. Therefore, several important clues may help in diagnosing and managing TPP: presentation in an adult male with no family history of periodic paralysis; presence of systolic hypertension, tachycardia, high QRS voltage, first-degree atrioventricular block on electrocardiography; presence of low-amplitude electrical compound muscle action potential on electromyography and no notable changes in amplitudes after low doses of epinephrinine; and typical acid-base and electrolyte findings such as normal blood acid-base state, hypokalemia with low urinary potassium excretion, hypophosphatemia associated with hypophosphaturia, and hypercalciuria. Immediate therapy with potassium chloride supplementation may foster a rapid recovery of muscle strength, but with a risk of rebound hyperkalemia. Nonselective beta-blockers may provide an alternative choice. Long-term therapy with definite control of hyperthyroidism completely abolishes attacks. Early diagnosis and prompt treatment of TPP prevent life-threatening complications of this treatable and curable disorder.

CONTEXT: The aim of this article was to review the clinical presentation, pathogenesis, and management of thyrotoxic periodic paralysis (TPP).

EVIDENCE ACQUISITION: A MEDLINE search was conducted for articles published during the last 40 yr based on the key words thyrotoxic periodic paralysis and hypokalemic periodic paralysis. A total of 281 primary articles and 168 references of the retrieved articles were also reviewed.

EVIDENCE SYNTHESIS: TPP is a common complication of hyperthyroidism in Asian men but is increasingly seen in Western countries. Hypokalemia and muscle paralysis results from a sudden intracellular shift of potassium and is not due to potassium deficiency. Clinical features of hyperthyroidism in patients with TPP may be subtle. Immediate potassium supplementation prevents serious cardiopulmonary complications and may hasten the recovery of muscle weakness. Nonselective beta-adrenergic blockers can ameliorate and prevent recurrence of the paralytic attacks. This episodic paralysis will remit with definitive control of hyperthyroidism. Increased sodium-potassium ATPase pump activity and enhanced insulin response in patients with TPP is postulated to contribute to the hypokalemia. The genetic predisposition for TPP is not entirely clear. Association of polymorphisms of the calcium channel alpha1-subunit gene with TPP has been noted.

CONCLUSIONS: Due to population mobility, TPP is increasingly common in Western countries. Early diagnosis and prompt treatment prevent life-threatening complications associated with hypokalemia and muscle weakness. Assaying of thyroid function in patients with hypokalemic paralysis distinguishes TPP from other forms of hypokalemic periodic paralysis.