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Journal of Clinical Anesthesia (2006) 18, 286 – 292

Case report

Thyrotoxic periodic paralysis and anesthesia report of a case and literature review
Daniel A. Diedrich MD, Denise J. Wedel MD*
Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
Received 18 January 2005; accepted 17 August 2005

Thyrotoxic periodic paralysis; TPP; Paralysis; Anesthesia; Hyperthyroidism; Hypokalemia

Abstract Thyrotoxic periodic paralysis (TPP) is a disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state. The disease primarily affects people of Asian descent, but can affect other ethnic groups. In Asians, the symptoms of thyrotoxicosis are distinct and usually precede the first paralytic episode, whereas in non-Asian populations, paralysis is the presenting symptom. If TPP has not been diagnosed and the patient has a surgical procedure during general or regional anesthesia, symptoms of the disease may be confused with other adverse perioperative events such as delayed recovery from neuromuscular paralysis. No specific anesthetic regimen is superior. Current TTP treatment recommendations involve treating the underlying hyperthyroid state. Other modalities such as b-blockade and potassium replacement are also important in the acute paralytic state. Future diagnostic and treatment innovations may lie in the genetic and molecular understanding of this disease. We present a case of an Asian male with known TPP undergoing general anesthesia, a brief case series involving 5 patients, and a review of the literature. D 2006 Elsevier Inc. All rights reserved.

1. Introduction
Thyrotoxic periodic paralysis (TPP) is a disease characterized by recurrent episodes of paralysis and hypokalemia in the setting of thyrotoxicosis. The disease primarily affects people of Asian descent, but can also affect other ethnic groups. In Asians, the symptoms of thyrotoxicosis are distinct and usually precede the first paralytic episode, whereas in non-Asian populations, paralysis is the presenting symptom. If TPP is undiagnosed and the patient has a surgical procedure during general or regional anesthesia, symptoms of the disease may be confused with other adverse perioperative

events such as delayed recovery from neuromuscular paralysis. We present a case of an Asian man with known TPP undergoing general anesthesia, a brief case series, and a review of the literature.

2. Case report
A 32-year-old Vietnamese man presented to the emergency department with a history of several hours of profound weakness in his lower extremities after a sudden collapse as he was walking down a flight of stairs. He denied paresthesias but reported lower extremity myalgias intermittently over the last several weeks. The symptoms were sudden in onset with no precipitating event and resolved spontaneously within a

* Corresponding author. 0952-8180/$ – see front matter D 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2005.08.016

Thyrotoxic periodic paralysis and anesthesia couple of hours. His medical history included a childhood head injury requiring surgery with no residual neurological deficits. There were no residual neurological deficits. His physical examination was unremarkable. Laboratory testing revealed a creatinine kinase (CK) of 1123 U/L (normal 52-336 U/L) and serum potassium (K+) of 3.0 mEq/L (normal 3.6-4.8 mEq/L). The final assessment was bfunctional weakness.Q At a neurological follow-up consultation 3 days later, there were no abnormal physical findings. Subsequent electromyography and brain magnetic resonance imaging were normal as were repeat CK and serum electrolytes. A week later, he awoke suddenly with lower extremity paralysis, upper extremity weakness, and diffuse myalgias. In the emergency department, he reported that the frequency of these attacks had increased to twice per week. Physical examination revealed intact sensation and reflexes with pronounced weakness in the lower and mild in the upper extremities. His K+ was 1.8 mEq/L and a thyroid-stimulating hormone (TSH) drawn the previous week was noted to be low (0.010 mIU/L, normal 0.30-5.0 mIU/L) with a high free thyroxin (3.1 ng/dL, normal 0.8-1.8 ng/dL). The diagnosis of TPP was made. The patient was administered oral potassium and his weakness spontaneously improved. He was dismissed home with oral potassium. The patient denied personal or family history of thyroid disorders. On direct questioning by an endocrinologist, he reported a mild tremor, loose stools, and palpitations that coincided with the weakness over the previous 2 months. He denied temperature sensitivities or skin changes, but noted a 7-lb weight loss over the same period. On examination, the thyroid was estimated at 30 to 35 g; 24-hour radioactive iodine uptake was normal at 15% (normal 8%-29%). The diagnosis of Graves’ disease was made. The patient was started on atenolol and scheduled for thyroidectomy. On the day of surgery, a preoperative K+ was 3.8 mEq/L. After intravenous placement, Ringer’s lactate solution was administered and standard monitors were applied. The patient received 8 mg of dexamethasone for postoperative nausea and vomiting and one mg of midazolam before intravenous induction with 50 mg of lidocaine, 50 lg of fentanyl, 200 mg of propofol, and 6 mg of vecuronium. The trachea was intubated atraumatically, an arterial catheter was placed, and

287 the patient was positioned for surgery. Anesthesia was maintained with isoflurane, nitrous oxide, vecuronium, and oxymorphone. An intraoperative K+ was 4.3 mEq/L. The patient was stable throughout the procedure. At the conclusion, the muscle relaxant was reversed with neostigmine and glycopyrrolate and the trachea extubated. The postoperative course was unremarkable.

3. Case series
Perioperative problems with TPP are rare. To our knowledge, there is only one case report in the western literature of a paralytic attack occurring after general anesthesia in a patient with TPP [1]. To further clarify this condition, we performed an institutional review board– approved retrospective chart review of all patients with a diagnosis of TPP who underwent general or regional anesthesia at our institution from 1976 to 2002. The primary aim of this review was to determine the incidence of postoperative ventilatory failure, perioperative paralysis, thyroid storm, electrocardiographic (ECG) abnormalities, or other adverse events in this population. We found 6 general anesthetics involving 5 patients using multiple general anesthetic techniques; no perioperative complications were noted (Table 1).

4. Review of the literature
Thyrotoxic periodic paralysis has similar clinical findings to familial hypokalemic periodic paralysis (FHPP). The primary difference between the two disease states is the presence of a thyrotoxic state in TPP. This review will focus specifically on TPP.

4.1. Clinical presentation
Thyrotoxic periodic paralysis is characterized by recurrent episodes of weakness primarily of the lower extremities. Proximal muscle groups are affected more than distal ones [2]. The attacks typically occur acutely at night [3] and may be heralded by muscle cramps, aches, and rigidity [4];

Table 1 Patient 1 2 3 4 5

Patients with TPP undergoing anesthesia at the Mayo Clinic (1976-2002) Age 34 50 32 56 43 58 Gender M M M M F Race C C V J F Surgical procedure Right inguinal hernia repair Laparoscopic cholecystectomy Total thyroidectomy Mitral valve repair Cholecystectomy/appendectomy Coronary artery bypass grafting Type of anesthesiaa GETA GETA GETA GETA GETA GETA Perioperative complicationsb None None None None None None

C indicates Caucasian; V, Vietnamese; J, Japanese; F, Filipino. a GETA (general endotracheal anesthesia) with induction drug, paralytic, opioid, volatile, and all but two anesthetics (cardiac) received a reversal medication. b Includes paralytic attack, perioperative ventilatory failure, thyroid storm, and ECG abnormalities from baseline.

288 symptoms vary in intensity from mild weakness to total paralysis. Sensation and mental status remain intact, but deep tendon reflexes are usually decreased or absent. Ocular, bulbar, and respiratory involvement is rare [5-8]. The affected muscle groups recover in reverse order of the paralysis, usually within 36 hours [2]. There is an increase in the incidence during the summer months [4]. The attacks can be triggered by emotional stress, cold, alcohol ingestion, menses, infection, and trauma [9,10]. Patients often learn to prevent an impending attack by exercising the involved muscles; the initial rest period after exertion is a time when attacks occur [11]. The paralysis occurs only when the patient is thyrotoxic [2], which is not specific to any one disease. Most patients have Graves disease [2,3], but TPP can also occur with a solitary toxic thyroid adenoma [11,12], TSH-secreting pituitary adenoma [13], and abuse of thyroid hormone [14]. Correction of the underlying thyrotoxic state aborts the attacks, but they can recur with the return of thyrotoxicosis [4]. Historically, supplemental potassium is reported to decrease the recovery time [15]. In Asians, the symptoms of thyrotoxicosis usually precede the first episode of TPP [2]. In non-Asian populations, the signs and symptoms are more subtle and a paralytic attack is more likely to be the presenting symptom [11,12]. This was the case in our patient. The two predominate biochemical abnormalities in TPP are thyrotoxicosis and hypokalemia. Serum thyroid testing typically reveals a thyrotoxic state with elevated triiodothyronine (T3) and/or thyroxine (tetraiodothyronine, T4) levels and a decreased or absent TSH level. Total body potassium stores are unchanged [16], but there is a decrease in serum potassium that tends to correlate to the severity of the paralysis [4]. However, paralysis can occur with normal or minimal changes in serum potassium as demonstrated in this case as well as others [17]. Hypokalemia is a result of an intracellular shift [18] and can range from mild to severe ranging from 1.1 to 3.4 mmol/L in one group of 19 patients [3,4]. Hypophosphatemia and hypomagnesemia also occur in TPP and are likely the result of intracellular shifts [3,9,19,20]. With resolution of the paralysis, rebound hyperphosphatemia is seen. Rhabdomyolysis secondary to electrolyte abnormalities results in mild elevations of CK [3]. During acute paralytic attacks, ECG signs of hypokalemia may be observed [21], including increased P wave (2.5 mm or greater in leads II, III, and aVF), widened QRS complexes, ST-segment depression, flattened T waves, and the appearance of U waves. As the potassium drops to 3.0 mEq/L, the T wave will decrease and merge with the increasing U wave [22]. Other ECG signs include variable degrees of AV block, tachycardia, ventricular fibrillation, and asystole [21,23-25].

D.A. Diedrich, D.J. Wedel with the diagnosis of TPP [4]. In thyrotoxic Japanese patients, the incidence of TPP is reported between 1.9% [26] and 8.8% [27]. In a Mayo Clinic retrospective review, 10 (eight white, one Filipino, and one Hispanic) of 8972 patients with hyperthyroidism were diagnosed with TPP, with the incidence of TPP at 0.1% to 0.2% for non-Asians [12]. Other ethnic groups can be affected. Ober [2] reviewed the case literature and found that of 82 reported cases in the continental United States, 32 (45%) were white, 17 (24%) Asian, 11 (15%) Hispanic, 5 (7%) black, and 5 (7%) American Indian. One (1%) was of other and 11 (13%) had unspecified ethnicity.

4.3. Pathophysiology
TPP is most prevalent in men. McFadzean and Yeung [4] noted that in 1366 Chinese patients with hyperthyroidism, 25 patients had TPP (23 men and 2 women). A similar low incidence in women was found by Okinaka et al. [26]. In 6333 cases of hyperthyroidism, 119 patients had TPP, 99 (8.2%) were men and 20 (0.4%) were women. In the 1992 review of Ober [2], the incidence of TPP in women was 3%. Most patients with TPP will present between the second and fourth decade [12,28]. Thyrotoxic periodic paralysis is a disease of skeletal muscle and not nerve or neuromuscular junction. The specific mechanism for TPP is unknown. A thyroid hormone–directed alteration in plasma membrane permeability to sodium and potassium was thought to be the underlying cause of TPP. The concentration of these ions is directly linked to the Na+/K+ ATPase activity that is increased in the thyrotoxic state [29-31] and to an even greater degree in TPP [32]. This increased activity theoretically results in an increased intracellular potassium transport resulting in hypokalemic paralysis. However, the increases in Na+/K+ ATPase activity that are commonly seen in thyrotoxicosis [29,33] do not all result in paralytic attacks. It is currently thought that the abnormality in Na+/K+ ATPase pumps due to thyrotoxicosis facilitates but is not necessary for hypokalemic periodic paralysis; the hypokalemia might be secondary to a Na+/K+ ATPase–independent potassium influx [34]. Attacks can occur during hypokalemia [35,36], normokalemia [37], or hyperkalemia [38], indicating that potassium flux is not the sole factor in paralysis. Increases in Na+/K+ ATPase activity can be seen after a glucose load with resultant increase in serum insulin. This cellular response may explain, in part, why paralysis typically follows carbohydrate loading [39]. Thyrotoxicosis is associated with greater b-receptor sensitivity [40]. The increased sensitivity and subsequent stimulation of these receptors by catecholamines like epinephrine can itself cause hypokalemia [41,42] and has been shown to worsen a paralytic attack [43] Paralysis can resolve by blocking these receptors with a nonselective b-blocker like propranolol [8,35,44]. The hyperadrenergic state of hyperthyroidism may also cause intracellular shifting

4.2. Epidemiology
Thyrotoxic periodic paralysis is a disease that primarily affects people of Asian descent. In 1366 cases of thyrotoxicosis in Chinese patients, 1.8% gave a history consistent

Thyrotoxic periodic paralysis and anesthesia of phosphate [9,19,20,45]. This has been postulated to also play a role in TPP [3]. Others have noted changes in intracellular calcium specifically decreases in Ca++ ATPase and rate of calcium uptake by the sarcoplasmic reticulum during paralytic attacks with normalization after the attacks [46]. Mutations in the L-type Ca++ channel in skeletal muscle sarcoplasmic reticulum have been found to cause FHPP [47], although the exact physiological impact of these mutations has not been identified [48]. Mutations in calcium channels that have been implicated in FHPP [49,50] have not been identified in patients with TPP to date. The fact that most patients with thyrotoxicosis are women [11,51], yet TPP is typically a disease of men, and the high incidence of TPP in Asians indicate that this disease has a genetic influence. However, there does not seem to be a familial predisposition for TPP (unlike FHPP) [11]; there is only one reported family with multiple TPP-affected members [52]. The HLA system has been studied extensively, but no consistent marker across ethnic groups has been found [2,53-57]. A mutation (R83H) in the KCNE3 gene was identified in a Caucasian man of Portuguese descent with TPP [58]. Two of his three children, who were asymptomatic, were also found to have the same mutation. The KCNE gene family encodes a group of membrane proteins associated with a potassium channel complex predominantly in skeletal muscle, which affects the resting membrane of skeletal muscle cells. The mutation decreases outward potassium flux producing a more positive resting membrane potential and a reduced repolarization capacity [59]. Recently, Tang et al [60] was unsuccessful in finding this mutation in 79 Chinese TPP patients. Other genes that have a major role in FHPP have been studied in patients with TPP. These genes, which code for the L-type alpha 1 calcium channel subunit, include the CACNA1S [49] and Ca v 1.1 [50]. Both genes are involved in coding for the alpha-1 subunit of the transmembranous L-type voltage-dependent calcium channel in skeletal muscle but do not seem to play a role in TPP. An association of three single nucleotide polymorphism of the Cav1.1 gene with TPP in southern Chinese men was recently found by Kung et al [61]. These polymorphisms lie near the thyroid hormone responsive element and they may affect its binding but the exact mechanism is unclear.

289 referred to in the literature were based on a study of 51 patients [63]. Potassium can be given either orally or intravenously. The traditional amount and frequency is 27 mEq of potassium chloride orally every 2 hours until muscle strength begins to recover. Recovery is usually seen after 6 hours of treatment and once there is a noticeable change in muscle strength, the frequency should be extended to every 4 hours until complete recovery is achieved [63]. During replacement, the patient needs to be carefully monitored. Caution may be exercised because rebound hyperkalemia can occur (40% in one study) [3,25]. It is recommended that potassium replacement therapy should not exceed 90 mEq (total IV/oral dose) in 24 hours. If there is failure for the paralysis to resolve with potassium supplementation, intravenous propranolol (one mg IV every 10 minutes times 3), a nonselective b-blocker, has been shown to terminate the attacks [8,44]. A report by Lin et al described two patients presenting with paralysis and hypokalemia who were treated with oral propranolol alone (3 mg/kg) with resolution of their symptoms and normalization of their serum potassium [64]. A nonselective b-blocker like propranolol should be considered a first-line agent in the treatment of acute TPP. Propranolol has also been shown to prevent attacks [35]. Selective b-blockers such as metoprolol do not abort or protect patients from paralytic attack [63]. The use of spironolactone has been described [4], as well as acetazolamide therapy [65]; however, their efficacy is sporadic and can even exacerbate the disease. Before definitive treatment, the patient should be advised to avoid precipitants (large carbohydrate loads, alcohol, excessive exercise, stress) [35].

4.5. Anesthetic concerns
There is no specific anesthetic method that is demonstrably superior for patients with TPP. However, several recommendations are supported by the current knowledge about this disease. Preoperative assessment in a patient with TPP should focus on the proper diagnosis and treatment of the thyrotoxicosis. Any elective surgery should be postponed until the patient is euthyroid. Signs and symptoms of thyrotoxicosis should be evaluated by history and physical examination. Management depends on the exact etiology but can include nonselective b-blockers (propranolol), the antithyroid drugs (propylthiouracil, methimazole, or carbimazole), inorganic iodine, and radioactive iodine or surgical removal of the thyroid [66]. All treatment modalities should be followed with serum biochemical markers to confirm a euthyroid state. With proper control of the hyperthyroidism, the risk of a paralytic attack is low. The treatment of TPP in patients who are thyrotoxic and undergoing emergent surgical procedures should focus on the cardiovascular management with intravenous b-blockers. Esmolol, a selective b1-blocker, has been recommended [67]; however, there are no data to support its use in

4.4. Treatment
The definitive treatment for TPP is correction of the hyperthyroid state by pharmacological or surgical measures. There is only one reported case in the literature where attacks of paralysis persisted during the euthyroid state [62]. Hypokalemia will eventually correct itself by shifting from the intracellular compartment. The standard therapy of potassium replacement is used to hasten recovery and prevent cardiac arrhythmias [24]. The treatment guidelines

290 TPP. Nonselective b-blockers (eg, propranolol) are the traditional choice. In euthyroid patients, the risk of a paralytic attack is low and initiation of b-blocker therapy is nonmandatory. However, the presence of comorbidities such as cardiac disease may indicate perioperative b-blockade [68]. The day before surgery, the patient should refrain from known triggers of TPP and anxiolytics should be given preoperatively if needed. There is no literature supporting routine preoperative laboratory testing except for thyroid testing as previously discussed. Should the patient complain of any symptoms of TPP, a serum potassium level should be checked and an ECG obtained. Treatment options should include propranolol, and supplemental potassium may be administered, but caution should be exercised because lifethreatening rebound hyperkalemia can occur. Empiric potassium supplementation in the asymptomatic patient is not recommended. Either regional or general anesthesia can be performed safely. All patients should have standard ASA monitoring, with additional monitoring dependent on comorbidities and the surgical procedure. No specific induction method is recommended. Glucose-containing intravenous solutions should be avoided; there is no evidence to support the use of Ringer’s lactate solution (with its 4 mEq/L of potassium) over normal saline. The patient should be kept normothermic. Any medication that could decrease serum potassium (eg, epinephrine, insulin, and albuterol) could potentially exacerbate a paralytic attack. When using neuromuscular blocking agents, proper titration and monitoring should be used. Neuromuscular monitoring can be done using any peripheral nerve [69]. However, as TPP can affect the muscles in both lower and upper extremities, it may be prudent to use the facial nerve because it is very rare for the bulbar muscles to be affected by the disease. Routine reversal of neuromuscular blockade is recommended. For symptomatic patients, paralytic attacks can mimic other causes of postoperative weakness and should be ruled out first. Treatment then should follow the guidelines as previously discussed. For asymptomatic patients, empirical postprocedure potassium levels are not recommended.

D.A. Diedrich, D.J. Wedel future diagnosis and treatment for patients with TPP lies in the genetic and molecular understanding of this disease.

We would like to acknowledge Julie Tuohy for her assistance in preparing this article.

[1] Robson NJ. Emergency surgery complicated by thyrotoxicosis and thyrotoxic periodic paralysis. Anaesthesia 1985;40:27 - 31. [2] Ober KP. Thyrotoxic periodic paralysis in the United States. Report of 7 cases and review of the literature. Medicine (Baltimore) 1992;71: 109 - 20. [3] Manoukian MA, Foote JA, Crapo LM. Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes. Arch Intern Med 1999;159:601 - 6. [4] McFadzean AJ, Yeung R. Periodic paralysis complicating thyrotoxicosis in Chinese. BMJ 1967;1:451 - 5. [5] Edelman J, Stewart-Wynne EG. Respiratory and bulbar paralysis with relapsing hyperthyroidism. BMJ (Clin Res Ed) 1981;283:275 - 6. [6] Crane M. Periodic paralysis associated with hyperthyroidism. CA Med J 1960;92:285 - 8. [7] Liu YC, Tsai WS, Chau T, Lin SH. Acute hypercapnic respiratory failure due to thyrotoxic periodic paralysis. Am J Med Sci 2004;327: 264 - 7. [8] Birkhahn RH, Gaeta TJ, Melniker L. Thyrotoxic periodic paralysis and intravenous propranolol in the emergency setting. J Emerg Med 2000;18:199 - 202. [9] Norris KC, Levine B, Ganesan K. Thyrotoxic periodic paralysis associated with hypokalemia and hypophosphatemia. Am J Kidney Dis 1996;28:270 - 3. [10] Ferreiro JE, Arguelles DJ, Rams H Jr. Thyrotoxic periodic paralysis. Am J Med 1986;80:146 - 50. [11] Magsino CH Jr, Ryan AJ Jr. Thyrotoxic periodic paralysis. South Med J 2000;93:996 - 1003. [12] Kelley DE, Gharib H, Kennedy FP, Duda RJ Jr, McManis PG. Thyrotoxic periodic paralysis. Report of 10 cases and review of electromyographic findings. Arch Intern Med 1989;149:2597 - 600. [13] Kiso Y, Yoshida K, Kaise K, et al. A case of thyrotropin (TSH)secreting tumor complicated by periodic paralysis. Jpn J Med 1990;29: 399 - 404. [14] Chen YC, Fang JT, Chang CT, Chou HH. Thyrotoxic periodic paralysis in a patient abusing thyroxine for weight reduction. Ren Fail 2001;23:139 - 42. [15] Tinker TD, Vannatta JB. Thyrotoxic hypokalemic periodic paralysis: report of four cases and review of the literature (1). J Okla State Med Assoc 1987;80:11 - 5. [16] Shizume K, Shishiba Y, Sakuma M, Yamauchi H, Nakao K, Okinaka S. Studies on electrolytes metabolism in idiopathic and thyrotoxic periodic paralysis. II. Total exchangeable sodium and potassium. Metabolism 1966;15:145 - 52. [17] Engel A. Thyroid function and periodic paralysis. Am J Med 1961;30: 327 - 33. [18] Shizume K, Shishiba Y, Sakuma M, Yamauchi H, Nakao K, Okinaka S. Studies on electrolyte metabolism in idiopathic and thyrotoxic periodic paralysis. I. Arteriovenous differences of electrolytes during induced paralysis. Metabolism 1966;15:138 - 44. [19] Nora NA, Berns AS. Hypokalaemic, hypophosphatemic thyrotoxic periodic paralysis. Am J Kidney Dis 1989;13:247 - 9.

5. Summary
Thyrotoxic periodic paralysis is a disease characterized by recurrent episodes of paralysis and hypokalemia in the setting of a thyrotoxic state. If a patient with TPP has a surgical procedure with general or regional anesthesia, symptoms of the disease may be confused with other perioperative events such as delayed recovery from neuromuscular blockade. No specific anesthetic regimen is superior. The current mainstay of treatment for TPP involves treating the underlying hyperthyroid state. Other modalities, such as b-blockade and potassium replacement, are also important during the acute state of paralysis. The

Thyrotoxic periodic paralysis and anesthesia
[20] Guthrie Jr GP, Curtis JJ, Beilman KM. Hypophosphatemia in thyrotoxic periodic paralysis. Arch Intern Med 1978;138:1284 - 5. [21] Chia BL, Lee KH, Cheah JS. Sino-atrial Wenckebach conduction in thyrotoxic periodic paralysis: a case report. Int J Cardiol 1995;47: 285 - 9. [22] Huszar RJ. Basic dysrhythmias: interpretation & management. St. Louis7 Mosby; 2002. p. 544. [23] Hsu YJ, Lin YF, Chau T, Liou JT, Kuo SW, Lin SH. Electrocardiographic manifestations in patients with thyrotoxic periodic paralysis. Am J Med Sci 2003;326:128 - 32. [24] Fisher J. Thyrotoxic periodic paralysis with ventricular fibrillation. Arch Intern Med 1982;142:1362 - 4. [25] Tassone H, Moulin A, Henderson SO. The pitfalls of potassium replacement in thyrotoxic periodic paralysis: a case report and review of the literature. J Emerg Med 2004;26:157 - 61. [26] Okinaka S, Shizume K, Iino S, et al. The association of periodic paralysis and hyperthyroidism in Japan. J Clin Endocrinol Metab 1957;17:1454 - 9. [27] Satoyoshi E, Murakami K, Kowa H, Kinoshita M, Nishiyama Y. Periodic paralysis in hyperthyroidism. Neurology 1963;13:746 - 52. [28] Lin YF, Wu CC, Pei D, Chu SJ, Lin SH. Diagnosing thyrotoxic periodic paralysis in the ED. Am J Emerg Med 2003;21:339 - 42. [29] Kjeldsen K, Norgaard A, Gotzsche CO, Thomassen A, Clausen T. Effect of thyroid function on number of Na-K pumps in human skeletal muscle. Lancet 1984;2:8 - 10. [30] Arnott RD, White R, Jerums G. Effect of thyroid status on ouabain binding to the human lymphocyte. J Clin Endocrinol Metab 1982;54:1150 - 6. [31] Khan FA, Baron DN. Ion flux and Na+,K+-ATPase activity of erythrocytes and leucocytes in thyroid disease. Clin Sci (Lond) 1987; 72:171 - 9. [32] Chan A, Shinde R, Chow CC, Cockram CS, Swaminathan R. In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis. BMJ 1991;303:1096 - 9. [33] Asano Y, Liberman UA, Edelman IS. Thyroid thermogenesis. Relationships between Na+-dependent respiration and Na+ + K+-adenosine triphosphatase activity in rat skeletal muscle. J Clin Invest 1976;57:368 - 79. [34] Oh VM, Taylor EA, Yeo SH, Lee KO. Cation transport across lymphocyte plasma membranes in euthyroid and thyrotoxic men with and without hypokalaemic periodic paralysis. Clin Sci (Lond) 1990;78:199 - 206. [35] Conway MJ, Seibel JA, Eaton P. Thyrotoxicosis and periodic paralysis: improvement with beta blockade. Ann Intern Med 1974; 81:332 - 6. [36] Lin SH, Lin YF, Halperin ML. Hypokalaemia and paralysis. QJM 2001;94:133 - 9. [37] Mehta SR, Verma A, Malhotra H, Mehta S. Normokalaemic periodic paralysis as the presenting manifestation of hyperthyroidism. J Assoc Physicians India 1990;38:296 - 7. [38] Adachihara K, Takagi Y. Case of thyrotoxic paralysis associated with hyperkalemic and hypokalemic paralytic attacks. Rinsho Shinkeigaku 1974;14:369 - 75. [39] Chan A, Shinde R, Chow CC, Cockram CS, Swaminathan R. Hyperinsulinaemia and Na+, K(+)-ATPase activity in thyrotoxic periodic paralysis. Clin Endocrinol (Oxf) 1994;41:213 - 6. [40] Levey GS, Klein I. Catecholamine–thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism. Am J Med 1990;88:642 - 6. [41] Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta2receptor stimulation by circulating epinephrine. N Engl J Med 1983; 309:1414 - 9. [42] Braden GL, von Oeyen PT, Germain MJ, Watson DJ, Haag BL. Ritodrine- and terbutaline-induced hypokalemia in preterm labor: mechanisms and consequences. Kidney Int 1997;51:1867 - 75. [43] Engel AG. Neuromuscular manifestations of Graves’ disease. Mayo Clin Proc 1972;47:919 - 25.

[44] Shayne P, Hart A. Thyrotoxic periodic paralysis terminated with intravenous propranolol. Ann Emerg Med 1994;24:736 - 40. [45] Body JJ, Cryer PE, Offord KP, Heath H III. Epinephrine is a hypophosphatemic hormone in man. Physiological effects of circulating epinephrine on plasma calcium, magnesium, phosphorus, parathyroid hormone, and calcitonin. J Clin Invest 1983;71:572 - 8. [46] Au KS, Yeung RT. Thyrotoxic periodic paralysis. Periodic variation in the muscle calcium pump activity. Arch Neurol 1972;26:543 - 6. [47] Fontaine B, Vale-Santos J, Jurkat-Rott K, et al. Mapping of the hypokalaemic periodic paralysis (HypoPP) locus to chromosome 1q31-32 in three European families. Nat Genet 1994;6:267 - 72. [48] Morrill JA, Brown RH Jr, Cannon SC. Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H. J Neurosci 1998;18:10320 - 34. [49] Chen L, Lang D, Ran XW, Joncourt F, Gallati S, Burgunder JM. Clinical and molecular analysis of Chinese patients with thyrotoxic periodic paralysis. Eur Neurol 2003;49:227 - 30. [50] Dias da Silva MR, Cerutti JM, Tengan CH, et al. Mutations linked to familial hypokalaemic periodic paralysis in the calcium channel alpha1 subunit gene (Cav1.1) are not associated with thyrotoxic hypokalaemic periodic paralysis. Clin Endocrinol (Oxf) 2002;56:367 - 75. [51] Bulow Pedersen I, Knudsen N, Jorgensen T, Perrild H, Ovesen L, Laurberg P. Large differences in incidences of overt hyper- and hypothyroidism associated with a small difference in iodine intake: a prospective comparative register-based population survey. J Clin Endocrinol Metab 2002;87:4462 - 9. [52] Kufs WM, McBiles M, Jurney T. Familial thyrotoxic periodic paralysis. West J Med 1989;150:461 - 3. [53] Yeo PP, Chan SH, Lui KF, Wee GB, Lim P, Cheah JS. HLA and thyrotoxic periodic paralysis. BMJ 1978;2:930. [54] Hawkins BR, Ma JT, Lam KS, Wang CC, Yeung RT. Association of HLA antigens with thyrotoxic Graves’ disease and periodic paralysis in Hong Kong Chinese. Clin Endocrinol (Oxf) 1985;23: 245 - 52. [55] Hawkins BR, Ma JT, Lam KS, Wang CC, Yeung RT. Analysis of linkage between HLA haplotype and susceptibility to Graves’ disease in multiple-case Chinese families in Hong Kong. Acta Endocrinol (Copenh) 1985;110:66 - 9. [56] Tamai H, Tanaka K, Komaki G, et al. HLA and thyrotoxic periodic paralysis in Japanese patients. J Clin Endocrinol Metab 1987;64: 1075 - 8. [57] Lazarus JH. Hyperthyroidism. Lancet 1997;349:339 - 43. [58] Dias Da Silva MR, Cerutti JM, Arnaldi LA, Maciel RM. A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. J Clin Endocrinol Metab 2002;87:4881 - 4. [59] Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA. MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell 2001; 104:217 - 31. [60] Tang NL, Chow CC, Ko GT, et al. No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients. Clin Endocrinol 2004;61:109 - 12. [61] Kung AW, Lau KS, Fong GC, Chan V. Association of novel single nucleotide polymorphisms in the calcium channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic paralysis. J Clin Endocrinol Metab 2004;89:1340 - 5. [62] Gandara DR, Fariss BL. Persistence of periodic paralysis following treatment of thyrotoxicosis: case report. Mil Med 1979;144:337 - 8. [63] Yeo PP, O’Neill WC. Thyrotoxicosis and periodic paralysis. Med Grand Rounds 1984;3:10 - 25. [64] Lin SH, Lin YF. Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis. Am J Kidney Dis 2001;37:620 - 3.

[65] Shulkin D, Olson BR, Levey GS. Thyrotoxic periodic paralysis in a Latin-American taking acetazolamide. Am J Med Sci 1989;297:337 - 8. [66] Cooper DS. Hyperthyroidism. Lancet 2003;362:459 - 68. [67] Thorne AC, Bedford RF. Esmolol for perioperative management of thyrotoxic goiter. Anesthesiology 1989;71:291 - 4. [68] Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery.

D.A. Diedrich, D.J. Wedel
Multicenter Study of Perioperative Ischemia Research Group. N Engl J Med 1996;335:1713 - 20. [69] Naguib M, Lien CA. Pharmacology of muscle relaxants and their antagonists. In: Miller RD, editor. Anesthesia. 6th ed. Philadelphia7 Elsevier-Livingstone; 2005. p. 481 - 572.