Department of Nephrology and Rheumatology, Georg-August-University Göttingen, Göttingen, Germany
Case
A 28-year-old Chinese scientist was admitted to our hospital with a diagnosis of psychogenic paralysis. The patient had been in good general health during the past month until he felt suddenly sick the evening prior to admission. During the night he experienced a progressive weakness, which started in both legs and spread to the upper extremities. In the early morning, he vomited several times and finally fell with paresis of the extremities. However, he was still able to call an ambulance and spontaneous movement in all four extremities was noted upon arrival, prompting the diagnosis of psychogenic paralysis.
On admission, the patient denied any form of drug treatment or substance abuse. There was no history of extended vomiting or diarrhoea. His weight had been stable and his past medical history was unremarkable. On physical examination he appeared well. He was fully oriented but somewhat agitated. The patient's temperature was 36.7°C, the pulse was 64/min and arrhythmic, and the blood pressure was 120/50 mmHg on both arms. No rash was detected although the skin was warm and dry. There was no lymphadenopathy. A moderately loud systolic murmur was best heard at the fifth left interspace radiating into the axilla. Thyroid palpation revealed a first-degree goiter, without any palpable nodules. On neurologic examination there was a slight and symmetric weakness of both legs (4/5) with normal muscle tone and no further abnormalities. Nevertheless, a CT scan of the head was performed which proved normal and the patient was transferred to our unit. Subsequently, an electrocardiogram displayed a second-degree AV block with Wenckebach phenomenon at a heart rate of 64. QT-intervals were prolonged (540 ms) and U-waves elevated as typical signs for hypokalaemia (Figure 1A).
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Question
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Further testing revealed a marked hyperthyreotic state. TSH was completely suppressed at 0.00 mU/ml, and all thyroid hormones were markedly increased: T3 429 ng/dl (normal range 89185), free T4 6.67 ng/dl (0.771.53), free T3 13.41 pg/ml (2.304.20). Antibody testing revealed positive values for anti-thyroid peroxidase (9099 mU/ml (<60)) and thyroid receptor (82.4 mU/ml (<914)) indicating a case of Grave's disease. There were normal values for creatinine clearance, sodium, potassium, and chloride excretion in 24-h urine. Measurement of plasma levels of ACTH, morning cortisol, and aldosterone as well as urinary excretion of cortisol and aldosterone yielded normal values too, excluding other possible causes of hypokalaemia. Thus, a diagnosis of thyrotoxic periodic paralysis (TPP) associated with severe hypokalaemia was made and therapy with thiamazol 40 mg/day and propranolol 20 mg four times daily was initiated. Upon intensive questioning, the patient reported that his father and sister in China had suffered from thyrotoxicosis as well. Furthermore, his father also had had episodes of paralysis during hyperthyroidism.
Extended clinical neurological examination was repeated 4 days after admission and demonstrated no pathological findings at all. At this time, the ECG showed a sinus rhythm at a rate of 87 b.p.m., normal axis, incomplete right bundle branch block and normal ST segments (Figure 1B). Chest X-ray and abdominal ultrasound were completely normal. Ultrasound examination of the thyroid gland showed a diffusely enlarged thyroid gland with a total volume of approximately 84 ml (43 ml right/41 ml left) without nodules. Because of his limited health insurance the patient refused any further investigations. He was discharged 5 days after admission and returned to China shortly thereafter.
TPP is a rare disease in Europe. The first case report considering a paralysis in association with hyperthyroidism was published in 1902 [1]. In most cases reported in the literature, Asian patients were affected. The incidence of TPP is about 0.10.2% among white hyperthyroid patients and about 1.98.8% among Asian hyperthyroid patients. Besides facultative symptoms of thyrotoxicosis (which our patient did not have) the symptoms of TPP during an attack are similar to those of familiar hypokalaemic periodic paralysis (HPP). Despite a typical clinical course attending physicians often diagnose psychogenic paralysis as was the case in our patient. Typically, the onset of symptoms is at night or in the early morning beginning with proximal muscular weakness in the legs. Some patients report preceding symptoms such as stiffness, cramps, and muscle pain [2]. Classically, the patient awakes and is not able to move arms or legs, whereas the motility of head and the ability to speak or swallow are not impaired. Often, paralysis begins over night. Attacks often take place after a meal rich of carbohydrates or after excessive physical exercise [2]. Other risk factors include exposure to cold, infection, trauma, menstruation, emotional stress, and medication including diuretics, insulin, ACTH, thyroxin, pilocarpine, physostigmine, adrenaline [3]. Paralysis usually lasts for 324 h and subsides even without treatment. The sensory system is not affected. The course is highly variable spanning from mild weakness to complete paralysis. Clinical neurological examination shows pareses with flaccid muscle tone and loss of tendon reflex response. Pathological reflexes or signs of upper motor neuron lesions are not detectable. Paralysis is often associated with various, mostly tachycardic arrhythmias. Diagnosis of hyperthyroid metabolism helps to distinguish TPP from other forms of hypokalaemic periodic paralysis. Diagnostic procedures should include control of electrolytes, glucose, blood gas analysis, thyroid hormone status and ultrasonographic, or radiological investigations of the thyroid gland. In cases of diagnostic uncertainty, the diagnosis of TPP may be confirmed by the glucoseinsulin test. Three grams of glucose per kg body weight given intravenously over 60 min plus 2x0.1 i.E./kg body weight insulin, if given to a still hyperthyroid patient, trigger a flabby paralysis within a latent period of several hours in TPP patients [3]. The glucoseinsulin test may trigger attacks in patients with familiar HPP as well as in hyperthyroid patients with TPP. However, if patients with TPP are tested during euthyroid state, this test will not provoke an attack [2]. Patients suffering from a familiar form of hypokalaemic periodic paralysis undergo paralysis attacks during normal thyroid metabolism, whereas in TPP the attacks occur in the context of thyrotoxicosis of any origin (Grave's disease, adenoma, thyroiditis, iatrogene, or abusive thyroxine intoxication) [2]. Clinical signs of thyrotoxicosis may be completely inapparent. The differential diagnosis between TPP and HPP is depicted in Table 1. Hypokalaemia does not represent a loss of total body potassium, but a shift of potassium into the intracellular compartment [2]. Clinically, symptoms subside after a few hours, when potassium returns into the extracellular compartment.
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Therapeutic options
With the onset of moderate symptoms, light muscle work and immediate potassium intake may prevent an attack in some cases. In established paralysis, treatment is indicated especially for prevention of cardiac arrhythmias. Potassium should be given either orally (32 mmol every 2 h) or intravenously (1020 mmol/h). Permanent substitution of potassium is not indicated, as electrolytes are within the normal range between attacks. In many patients ß-adrenergic blocking is successful during the attack, reducing frequency and severity of episodes. Recently, the use of high doses of propranolol has been propagated as a therapeutic option [4]. Thiamazole should be given to treat hyperthyroidism. Until a euthyroid metabolism is maintained, glucose loading and other risk factors should be avoided. Acetazolamide is effective as a prophylaxis of attacks in HPP, whereas in TPP it may even aggravate the severity and frequency of attacks [2].
Notes
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References