Hypokalemic thyrotoxic periodic paralysis: a case series

Case Reports

CJEM 2003;5(5):353-355

Abstract

Résumé

Case reports | Discussion | Conclusion | References

Case reports

Over a 5-year period, 9 men and 1 woman presented to the emergency departments of Western Hospital and Sunshine Hospital in Melbourne, Australia. Six of the patients were Vietnamese, and the remaining 4 were Filipino, Korean, Laotian and Caucasian. Their ages ranged from 18 to 58 years (mean 34).

In 9 of the 10 patients, the onset of lower-limb paraplegia occurred at night, between 10:00pm and 6:00am. Prior to their paralysis, 3 patients described a physically demanding day at work, 2 reported symptoms of a viral upper respiratory tract infection, 1 had eaten a large meal, another had undergone general anesthesia for circumcision 2 days earlier and 1 had been on an alcohol binge.

All 10 patients described symmetrical, proximal lower-limb weakness. Deep tendon reflexes were diminished in 1 patient, increased in another and normal in 8. None of these patients had sensory findings, cranial nerve abnormalities, ocular signs or respiratory muscle involvement. The most common hyperthyroid findings were a goiter in 4 patients, tachycardia in 4 patients, a thyroid bruit in 2, hyperreflexia in 2, and tremor in 1.

Five patients had a pre-existing diagnosis of hyperthyroidism, and the remainder were diagnosed during their index admission, based on clinical features and biochemical confirmation in 9 cases (low thyroid-stimulating hormone [TSH] levels along with elevated free thyroxine [FT₄] or free triiodothyronine [FT₃]). One patient was biochemically euthyroid. The most common hyperthyroid symptoms were weight loss, tremor, palpitations, heat intolerance, diarrhea and increased appetite. Eight of the 10 were diagnosed with Grave's disease, and 2 had thyrotoxicosis of uncertain etiology.

All patients were hypokalemic, with potassium levels ranging from 1.6 to 2.4 mmol/L (normal 3.5-5.5 mmol/L) (Table 1). Five had decreased phosphate (PO₄) levels, 4 had decreased magnesium (Mg), and 2 had decreased calcium (Ca). Eight patients had electrocardiograms and all were abnormal -- 4 showed U waves, and 4 showed sinus tachycardia (ST) depression with T-wave flattening.

Discussion

This study and others show that thyrotoxic periodic paralysis (TPP) is a disease of young Asian males. TPP is 10 times more common in Asian than in non-Asian countries,¹ and although thyrotoxicosis most often affects females, TPP has been reported in 0.11% of Japanese women (v. 4.3%-8.2% of Japanese men) and in 0.17% of Chinese women (v. 12.9% of Chinese men).²

In this series, 90% of patients experienced symptom onset between 10:00pm and 6:00am. These findings are similar to those of Yeo and colleagues, who reported that 88.5% of TPP patients in a Singapore series had symptom onset between 6:00pm and 8:00am.³ Previous authors have identified precipitating factors such as ingestion of a high carbohydrate food load, strenuous physical activity followed by a rest, surgery, and insulin use, and many of these factors were apparent in this case series.

Symmetric proximal lower-limb muscle weakness is characteristic of TPP, but asymmetric involvement may occur. The absence of ocular and respiratory involvement differentiates TPP from myasthenia gravis and Guillain-Barré Syndrome (GBS); however, respiratory involvement is rarely an early finding in GBS. Sensation is preserved in TPP, and deep-tendon reflexes are usually depressed, although the majority of patients in this study had normal deep-tendon reflexes. In cases of proximal muscle weakness, emergency physicians should also consider proximal myopathy, spinal cord lesions, electrolyte abnormalities (including diuretic abuse), primary hypoaldosteronism, and alcoholism in the differential diagnoses. It is important to remember that hysteria and other psychological conditions may present as muscle weakness.

Although any thyroid disorder may be associated with TPP, Grave's disease is the most common.⁴ The Asian literature suggests that thyrotoxicosis is usually obvious at presentation, whereas Western authors tend to emphasize the subtlety of hyperthyroid symptoms.⁴ In this series, 7 patients had obvious hyperthyroid symptoms, but among the others it was only after directed questioning and thyroid function testing that the diagnosis of hyperthyroidism was made. This may reflect an unfamiliarity with the condition and the subtlety of symptoms. TPP can also be the first presentation of hyperthyroidism in an otherwise asymptomatic person.⁵

Hypokalemia in TPP is related to intracellular shifting rather than a total body potassium deficiency.⁶ Hypophosphatemia and mild hypomagnesemia are also common findings, but are not consistent features of TPP.² The precise pathophysiology underlying TPP is not completely clear. A genetic component has been postulated, given its propensity for Asian men. A number of factors such as increased activity of the sodium (Na⁺), potassium (K⁺) adenosine triphosphatase (ATPase), increased responsiveness to ß-adrenergic stimulation, disturbance in intracellular calcium (Ca⁺) shifts in muscle, hypophosphatemia and exaggerated insulin response to carbohydrate loading may be responsible.^4,7 The most common ECG findings include U waves, ST depression and T-wave flattening and sinus tachycardia. Sinus arrest and ventricular fibrillation are uncommon but potentially lethal.

Without treatment, TPP victims will spontaneously recover muscle strength over a period of 36 hours as K⁺ shifts out of cells into the extracellular space. Potassium supplementation will prevent cardiac arrhythmias and hasten recovery during the acute paralysis; however, potassium does not consistently prevent recurrent attacks.⁵ Although there are no randomized trials addressing the value of potassium supplementation, one author suggests administering 27 mEq of oral potassium chloride every 2 hours for 6 hours or until muscle power begins to recover, then every 4 hours.³ Two patients in the current study suffered rebound hyperkalemia, which is a potential hazard associated with aggressive potassium treatment during acute paralysis.²

The definitive treatment for TPP is control of the hyperthyroid state. Once patients are euthyroid, episodes of paralysis generally cease.⁴ Avoiding high carbohydrate meals is recommended, and propranolol may reduce the likelihood of relapse until the euthyroid state is achieved.⁸ In this study, 1 patient who had previously been treated successfully with radioactive iodine for Grave's disease proved an exception to the rule. Despite being clinically and biochemically euthyroid on admission, he presented with hypokalemic periodic paralysis responsive to potassium. One other case reported described periodic paralysis that persisted in the euthyroid and hypothyroid state, and resolved following thyroid replacement.⁹ Therefore, when faced with an euthyroid patient who has hypokalemic periodic paralysis, it is appropriate to ask about previously treated hyperthyroidism.

Conclusion

TPP is a rare complication of hyperthyroidism. The diagnosis is most likely in young Asian men presenting with hypokalemia, early morning weakness and proximal lower extremity paralysis. Potassium should be administered in the acute setting to hasten recovery and prevent cardiac arrhythmias, but achievement of the euthyroid state is the definitive treatment.

References

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