Elsevier

Mayo Clinic Proceedings

Volume 80, Issue 1, January 2005, Pages 99-105
Mayo Clinic Proceedings

Concise Review for Clinicians
Thyrotoxic Periodic Paralysis

https://doi.org/10.4065/80.1.99Get rights and content

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 lowamplitude 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. Non-selective β-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.

Section snippets

EPIDEMIOLOGY

Approximately 2% of patients with thyrotoxicosis in China and Japan reportedly have TPP.2, 8 It has been recognized also in Thai, Filipino, Vietnamese, Korean, and Malaysian populations. In the United States, the incidence of TPP in the non-Asian population is approximately one tenth (0.1%-0.2%) that found in Asian countries.9 Despite a higher incidence of thyrotoxicosis in women, TPP occurs predominantly in men; the male-female ratio is approximately 20:1. The racial differences and male

ETIOLOGY

Thyrotoxic periodic paralysis can occur in association with any of the causes of hyperthyroidism. The most common cause of TPP in hyperthyroidism is Graves disease. Patients with TPP have been reported with toxic nodular goiter, iodine-induced thyrotoxicosis, excessive thyroxine use, solitary toxic thyroid adenoma, lymphocytic thyroiditis, and thyrotropin-secreting pituitary adenomas (Table 1). Unlike with other causes of primary hyperthyroidism, the presence of detectable or normal levels of

PATHOPHYSIOLOGY

The pathogenesis of TPP is related to thyrotoxicosis per se, rather than to the specific disease causing hyperthyroidism. The Na+,K+-ATPase pump activity in platelets and skeletal muscle cells was increased in patients with thyrotoxicosis and periodic paralysis compared with patients with thyrotoxicosis and no paralysis.13, 14 Hyperthyroidism results in a hyperadrenergic state.15 β2-Adrenergic stimulation in muscle cells may directly induce cellular potassium uptake by increasing intracellular

CLINICAL MANIFESTATIONS

The initial episode of TPP usually occurs in persons aged 20 to 40 years in contrast with the initial episode of FPP that usually occurs in persons younger than 20 years. Clinically, attacks of TPP are indistinguishable from those of FPP. Prodromal symptoms include muscle aches, cramps, and muscle stiffness. Weakness usually begins in the proximal muscles of the lower extremities and can progress to flaccid quadriplegia. The paralysis is usually symmetrical but may be asymmetrical and limited

LABORATORY FINDINGS

Although thyroid function tests provide the definitive diagnosis for TPP, they usually are not available in the emergency department. Furthermore, despite the name, attacks of periodic paralysis may precede overt signs or symptoms of hyperthyroidism, as mentioned previously. Any important clues suggestive of TPP, such as those in the following laboratory findings, may aid in the diagnosis.

DIFFERENTIAL DIAGNOSIS

The neuromuscular picture of TPP is almost indistinguishable from that of other causes of hypokalemia and paralysis (non-TPP). The etiologies of non-TPP include other hypokalemic disorders causing a transcellular shift of potassium, excessive renal potassium wasting, and large gastrointestinal potassium losses. As Table 2 shows, TPP can be distinguished from non-TPP simply on the basis of a family history of paralysis, drug use, blood acid-base state, blood pressure, and urinary potassium and

Emergency Therapy

Body potassium stores are normal in patients with TPP. The aim of potassium supplementation is to normalize the plasma potassium concentration instead of repairing a potassium deficit.39 The traditional treatment of severe attack is immediate intravenous or oral potassium chloride administration to hasten muscle recovery and to prevent cardiac arrhythmia and respiratory arrest. However, the danger of exogenous potassium administration is that potassium is released from cells rapidly when

CONCLUSIONS

Thyrotoxic periodic paralysis has become more common in emergency departments of Western countries because of the increasing number of immigrants from Asia. Because thyroid function tests usually are not available in emergency departments and the symptoms of hyperthyroidism are often indistinct in many patients with TPP, rapid recognition and termination of TPP is mandatory to avoid this potentially fatal, but readily treatable, disorder. A careful medical history, clinical examination, and

Questions About TPP

  • 1.

    Which one of the following statements regarding the epidemiology of TPP is false?

    • a.

      TPP is most common in Asia

    • b.

      The incidence of TPP in the United States is approximately one tenth that in Asian countries

    • c.

      TPP is more common in women than in men

    • d.

      TPP occurs usually in the early morning or late evening

    • e.

      TPP attacks are most common in summer and autumn

  • 2.

    Which one of the following statements regarding the pathophysiology of TPP is incorrect?

    • a.

      The pathogenesis of TPP is related to the specific

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    This work was supported in part by a research grant (TSGH-C93-51) from the Tri-Service General Hospital and by the C. Y. Chai Foundation for Advancement of Education, Science and Medicine.

    A question-and-answer section appears at the end of this article.

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