review article thyrotoxic periodic paralysis: clinical...

Review ArticleThyrotoxic Periodic Paralysis: Clinical Challenges

Abhishek Vijayakumar,1,2 Giridhar Ashwath,1 and Durganna Thimmappa1

1 Department of General Surgery, Victoria Hospital, Bangalore Medical College and Research Institute, Bangalore 560002, India2 #128 Vijay Doctors Colony, Konanakunte, Bangalore, Karnataka 560062, India

Correspondence should be addressed to Abhishek Vijayakumar; [email protected]

Received 1 December 2013; Accepted 18 January 2014; Published 20 February 2014

Academic Editor: Massimo Tonacchera

Copyright © 2014 Abhishek Vijayakumar et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset ofhypokalemia and paralysis.The condition primarily affects the lower extremities and is secondary to thyrotoxicosis.The underlyinghyperthyroidism is often subtle causing difficulty in early diagnosis. Factors like high-carbohydratemeal exercise, steroid, and stresscan precipitate an attack of TPP. Evidence is building up showing role of genetic mutations in Kir2.6 channel in the pathogenesisof TPP. Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle ofhypokalemia. Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes are characteristic of TPP.Treatment with low-dose potassium supplements and nonselective beta-blockers should be initiated upon diagnosis, and the serumpotassium level should be frequently monitored to prevent rebound hyperkalemia.

1. Introduction

Association of periodic paralysis and thyrotoxicosis had beendocumented by Rosenfeld as early as 1902 [1]. Thyrotoxicperiodic paralysis (TPP) is more commonly reported inoriental Asians [2]. It has also been reported from thewestern countries as a result of migration of different ethnicpopulations [3]. TPP is characterized by acute onset of severehypokalemia and profound proximal muscle weakness inpatients with thyrotoxicosis [4]. TPP is commonly misdi-agnosed in Western countries because of its similarities tofamilial periodic paralysis. The neuromuscular presentationsof both are identical and physicians need to look for subtlefeatures of hyperthyroidism in the presence of hypokalemicperiodic paralysis. Early diagnosis not only aids in definitivemanagement with nonselective beta-blockers and correctionof hyperthyroidism, but also prevents the risk of reboundhyperkalemia due to excessive potassium replacement.

2. Discussion

Hypokalemia-related medical emergencies vary frommuscleweakness to paralysis and are called hypokalemic paralysis.

The etiology of hypokalemic paralysis can be generallyclassified into two groups: hypokalemic periodic paralysis,due to shift of potassium into the intracellular space without atotal potassium deficit; and nonhypokalemic periodic paral-ysis, due to a large potassium deficit via gastrointestinal orrenal loss. Among the hypokalemic periodic paralysis, famil-ial hypokalemic periodic paralysis (FPP) is themost commoncause inWestern countries, and thyrotoxic periodic paralysis(TPP), characterized by the triad of acute hypokalemiawithout total body potassium deficit, muscle paralysis, andthyrotoxicosis, is the most common cause in Asia.

3. Epidemiology

The incidence of TPP in Chinese and Japanese thyrotoxicpatients has been reported at 1.8% and 1.9%, respectively [2],whereas inNorth Americans a 0.1%–0.2% [5]. In the Chinese,TPP occurs in 13% of male and 0.17% of female thyrotoxicpatients, in a series published in 1967 [4]. The male tofemale ratio ranges from 17 : 1 to 70 : 1 despite the fact thathyperthyroidism is more common in females (female-to-male ratio of 9 : 1) [6].

Hindawi Publishing CorporationJournal of yroid ResearchVolume 2014, Article ID 649502, 6 pageshttp://dx.doi.org/10.1155/2014/649502

2 Journal of Thyroid Research

4. Pathophysiology

The pathogenesis of TPP remains unclear. Sodium, chloride,calcium, and potassium channels on cell membranes areresponsible for membrane excitability and muscle contrac-tions. Disruption of any of these cellular transport mecha-nisms, especially 3Na+/2K+ ATPase pump, may cause abnor-malities in muscle contractibility and paralysis.

The important role of Na+-K+ ATPase pumps in thepathogenesis of TPP is supported by the finding that theiractivity in the skeletal muscle is significantly increased.Thyroid hormone can stimulate Na+-K+ ATPase in skeletalmuscle by genomic mechanism, acting on the thyroid hor-mone responsive elements to upregulate the transcriptionof the gene encoding Na+/K+ ATPase and via nongenomicmechanisms by enhancing the intrinsic activity or promotingmembrane insertion of the pump. Thyrotoxic patients withPP have been found to have higher sodium pump activitythan those without paralytic episodes [7]. Catecholaminecan also increase Na+/K+-ATPase activity in skeletal muscle[8].The enhanced beta-adrenergic response in thyrotoxicosisfurther increases Na+/K+-ATPase activity.

Hyperinsulinemia is also observed in acute attack ofTPP, and the release of insulin in response to oral glucosechallenge is exaggerated in TPP patients, supporting the ideathat insulin participates in the pathogenesis of hypokalemiain TPP [9]. Insulin-response sequences are present in theupstream region of Na+/K+-ATPase genes, and insulin hasbeen shown to stimulate Na+/K+-ATPase activity [10]. Theeffect of insulin may account for the observation that ahigh-carbohydrate diet can be a precipitating factor for TPP.Sympathetic stimulation of insulin release in pancreas 𝛽-cells provides additional rationale for using nonselective 𝛽-blockers to treat acute hypokalemia and paralytic attack ofTPP.

Androgens have been reported to increase the expres-sion and activity of the Na+/K+-ATPase [11, 12]. Testos-terone enhances hypertrophy of myoblasts and thus causeshigher muscle-to-body mass ratio and total Na+/K+-ATPaseabundance in males. Catecholamines, a strong activator ofNa+/K+-ATPase activity, have been found to be releasedmore in males in response to experimental stress [13]. Thepreponderance of TPP attacks in the morning may also stemfrom higher plasma catechol-amines and sympathetic tone inthe late morning [14]. With respect to the seasonal variation,increased outdoor activity with increased perspiration ofpotassium and ingestion of sugar-containing cold beveragesmay be responsible for the higher prevalence of TPP attacksin the summer and fall.

Exercise releases potassium from the skeletal muscles,whereas rest promotes influx of potassium.This explains whyparalytic attacks occur only during recovery from exerciseand resumption of exercise can abort an attack. Overall, itappears that patients with TPP have an underlying predispo-sition for activation of Na/K-ATPase activity, either directlyby thyroid hormone or indirectly via adrenergic stimulation,insulin, or exercise. Traditional views regarding mechanismof paralysis are shown in Figure 1.

T4 Increased insulin release

Disrupted ion channels

Intracellular potassium shif

Hypokalemia

Hyperpolarization

Periodic paralysis

↑ Adrenergic response

↑ Na/K ATPase

Figure 1: Mechanism of paralysis in TPP.

Activation of Na+/K+ ATPase cannot be the only mech-anism for TPP, because only a minority (∼2%) of patientswith hyperthyroidism develop hypokalemic paralysis. Theincreased Na-K ATPase activity in muscle may be compen-sated by increased potassium efflux preventing developmentof hypokalemia. It was seen that the total intracellular pota-ssium content measured in the diaphragm muscle of athyrotoxic mouse is unchanged from the normal [15].

Additional factors such as decreased potassium effluxmight cause clinically significant hypokalemia. Studies haveshown that the outward Kir current is decreased in inter-costal muscle fibers of both patients with TPP and familialhypokalemic periodic paralysis [16]. Moreover, insulin andcatecholamine not only activate Na+/K+ ATPase but alsoinhibit Kir channels [17].

Recent studies have shown that mutations in the geneencoding Kir2.6, a skeletal muscle-specific Kir channel, areassociated with TPP and predispose these patients to acuteparalytic attacks. A study by Ryan et al. [18] showed that theprevalence of Kir2.6 mutation was up to 33% in Caucasiansand Brazilians with TPP. Thyroid hormone upregulates thetranscription of Kir2.6 through an upstream thyroid hor-mone responsive element in the promoter region of channelgene. Cheng et al. [19] found three additional loss-of-functionmutations in Kir2.6 channels in patients with TPP as well assporadic periodic paralysis. Cheng et al. also reported thatKir2.6 forms functional homotetramer and heterotetramerwith Kir2.1, another Kir channel in the skeletal muscle. Kir2.6mutants exert a dominant negative effect on both WT Kir2.1and Kir2.6 channels.

Evidence is building up showing role of geneticmutationsin Kir2.6 channel in the pathogenesis of TPP. Loss of functionof Kir2.6 together with increased activity of Na+/K+ ATPasemay trigger a positive feed-forward cycle of hypokalemia,

Journal of Thyroid Research 3

leading to paradoxical depolarization with consequent inac-tivation of Na+ channel and muscle inexcitability [20].

The central to pathophysiology of skeletal muscle paraly-sis in hypokalemic periodic paralysis is paradoxical depolar-ization. The resting membrane potential should hyperpolar-ize when extracellular K+ decreases. However, muscle fibersfrom patients with hypokalemic periodic paralysis depolar-ize under low extracellular K+ concentrations (<3mEq/L).This hypokalemia-induced paradoxical depolarization of theresting membrane potential leads to inactivation of Na+channels, rendering them unexcitable.

In familial Hypokalemic periodic paralysis paradoxicaldepolarization is caused by mutations in the voltage sensorof Nav1.4 and Cav1.1 channels giving imbalance betweeninward leak current and outward K current. In TPP, reducedoutward K+ current because of loss-of-function mutationsof Kir2.6 causes a similar imbalance between inward leakcurrent and outward K+ current, and it results in paradoxicaldepolarization.

5. Clinical Features

Patients are usually young adult males 20–40 yr of age. Theattack is characterized by recurrent, transient episodes ofmuscle weakness that range frommild weakness to completeflaccid paralysis. Neurologic examination during an attackdemonstrates weakness, usually affecting proximalmore thandistal muscles, and the legsmore than the arms.Mildmyalgiais a complaint in less than half of patients [21]. Decreasedmuscle tone with hyporeflexia or areflexia is typical, althoughnormal or hyperactive reflexes may be seen in some cases.Sensory function is not affected. The muscles affected maybe asymmetrical and bowel and bladder function are neveraffected. In one series, tachycardia (mean heart rate =105 bpm) was noted at presentation and distinguished thesepatients from those with familial hypokalemic periodic par-alysis [22]. Exceptional cases of bulbar weakness and res-piratory weakness requiring ventilatory support have beenreported in TPP [23]. In severe cases of hypokalemia, evenfatal, arrhythmias (sinus arrest, second degree atrioventricu-lar [AV] block, ventricular fibrillation, and ventricular tachy-cardia) have been seen. Patients may experience recurrentepisodes of weakness that last from a few hours up to 72 h,with complete recovery in between the attacks. Table 1 showssome salient features of TPP.

As with hypokalemic PP, attacks in thyrotoxic PP may beprecipitated by events that are associated with an increasedrelease of epinephrine or insulin, both of which cause move-ment of potassium into cells and low potassium blood levels.Precipitating factors include high carbohydrate loads, stren-uous exercise, trauma, acute URI, high-salt diet, emotionalstress, exposure to cold, alcohol ingestion, menstruation, anduse of drugs such as corticosteroids, epinephrine, acetazo-lamide, and nonsteroidal anti-inflammatory drugs. In a largestudy by Chang et al. [24] in 2013 one hundred and thirty fivepatients of TPP were followed up for 10 years. It was foundthat only 34% had identifiable precipitants. TPP patients withand without known precipitating factors had no significantdifferences in their clinical and biochemical findings. A high

Table 1: Clinical features of TPP.

Clinical manifestations of thyrotoxic periodic paralysisGeneral

Male predominance; initiation at age 20 to 40Periodic flaccid paralysis of proximal muscles, mainly oflower extremitiesNegative family history of similar symptomsHypertensionSubtle clinical features of hyperthyroidism

Laboratory findingsHypokalemia, hypophosphatemia, and mild hypomagnesemiaNormal acid-base balanceLow potassium excretion rate (low urinary potassium-creatinine ratio and low TTKG)Hypercalciuria and hypophosphaturiaAbnormal thyroid function tests (low TSH; elevated free andtotal T4 and T3; increased T3 uptake)

Electrocardiographic abnormalitiesSinus tachycardiaHypokalemic changes: prominent U wave, prolonged PRinterval, increasedP-wave amplitude, widened QRS complexesFirst-degree atrioventricular blockAtrial and ventricular arrhythmias

Electromyography: low-amplitude compound muscle actionpotential with no change after epinephrine.TTKG indicates transtubular potassium gradient (a semiquantitativeindex of the activity of the potassium secretory process calculated as[urine K/(urine osmolality/plasma osmolality)]/plasma K); TSH: thyroid-stimulating hormone; T4: serum thyroxine; T3: triiodothyronine.

carbohydrate or strenuous exercise was identified as precip-itant in only 12 and 7%, respectively. Though high carbohy-drate meal has been associated with an attack of TPP, stan-dardization of glucose meal test for diagnosis is not available.It was found that only 10 of the 55 (18%) patients developedhypokalemia after glucose loading of 2 g/Kg. Also in arecent study none of the 51 cases of TPP developed symptomsafter glucose loading test [25]. Although attacks of weaknessmay occur at any time of the day, a high frequency of attacksat night or early in the morning has been reported in TPP.A seasonal variation has also been suggested, with morefrequent attacks in summer months.

Most patients with TPP have only mildly elevated serumthyroid hormone levels and only about 10% of patients mayhave mild thyrotoxic symptoms [6]. Using theWayne’s index,a reliable quantitative score of hyperthyroid severity, it wasfound that only 17% of TPP patients had toxic thyrotoxicosis(score > 19), supporting the notion that most TPP patientshave equivocal symptoms [24].

Although the majority of cases of thyrotoxicosis associ-ated with TPP are due to Graves’ disease, TPP can appearwith thyrotoxicosis of any origin. Patients with TPP havebeen reported with thyroiditis [26, 27], toxic adenoma [28],toxic nodular goiter [29], TSH-secreting pituitary adenoma


Table 2: Differential diagnosis of hypokalemic paralysis.

Type of potassium Imbalance Cause

Transcellular shift

Drugs (tocolytics, theophylline toxicity, chloroquinetoxicity, insulin overdose)Thyrotoxic periodic paralysisFamilial periodic paralysisSporadic periodic paralysisBarium poisoning

Renal loss of potassium

Drugs: diureticsPrimary hyperaldosteronismPseudohyperaldosteronism: licorice ingestionBartter’s syndrome, Gitelman’s syndromeRenal tubular acidosisOther: nephrotic syndrome, acute tubular necrosis, diabeticketoacidosis, and ureterosigmoidostomy.

Gastrointestinal loss of potassium

Celiac diseaseTropical sprueInfectious diarrhea: Salmonella enteritis, Strongyloides enteritis, andYersinia enterocolitisShort bowel syndrome

[30, 31], ingestion of T4 or T3 [32, 33], inadvertent iodineexcess [34], subacute thyroiditis of de Quervain [35], amio-darone therapy [36], radiation thyroiditis withGraves’ disease[37], and nutraceuticals containing tiratricol [38].

During an attack of paralysis or weakness serum, potas-sium level is usually less than 3.0mmol/liter and can be as lowas 1.1mmol/liter. Occasionally if the patient is at the recoverystage of the paralysis, serum potassium can be normal. Inaddition to hypokalemia, there may be hypophosphatemiaand hypomagnesemia. Mild to moderate hypophosphatemiain the range of 0.36–0.77mmol/liter has been reported in twothirds of cases [39]. Serum phosphate level returns to normalwithout supplementation when the patient recovers from theweakness. Serum creatine phosphokinase of muscle origin iselevated in about two thirds of patients, particularly amongthose whose attacks are precipitated by exercise. The compli-cation of rhabdomyolysis may occur in a severe attack.

Electrocardiographic findings may be characteristic ofhypokalemia, with increased P-wave amplitude, prolongedPR interval, widened QRS complexes, decreased T-waveamplitude, and U waves. Unlike hypokalemia from othercauses, sinus tachycardia predominates in patients with TPP.Other electrocardiographic abnormalities include atrioven-tricular block, atrial fibrillation, ventricular fibrillation, andasystole [40, 41].

TPP must be differentiated from other causes of hypo-kalemic periodic paralysis. (Table 2) Workup for othercauses of hypokalemia include urinary potassium excretion(>30mEq indicates urinary loss), arterial blood gas foracidosis, urinary potassium to creatinine ratio which is <13in TPP.

6. Treatment

Management of TPP includes correction of hypokalemia andtreatment of the underlying hyperthyroid state. Traditionally,patients are given intravenous or oral potassium to hastenmuscle recovery and prevent cardiopulmonary complica-tions; however, there is a danger of rebound hyperkalemiadue to release of potassium and phosphate from the cells onrecovery.

One prospective study compared treatment with intra-venous potassium chloride to normal saline infusion andfound a shorter recovery time with use of potassium (6.3 vs.13.5 hours) [42]. In a retrospective case series, patients whoreceived intravenous potassium recovered more quickly thanthosewho received oral supplementation [43].Theremay be adelayed response of a few hours following potassium admin-istration [44]. Required doses of potassium supplementationare variable and range from 10 to 200mEq. Rebound hyper-kalemia occurred in approximately 40% of patients with TPP,especially if they received >90mEq of potassium chloridewithin the first 24 hours. There is a positive correlationbetween the dose of potassium chloride administered andthe degree of rebound hyperkalemia. Patients receiving atotal dose of ≤50mEq of potassium chloride rarely developrebound hyperkalemia. Lower doses of potassium chloridemay be effective while lowering the patient’s risk of hyper-kalemia.Thus KCl supplementation should be given at a slowrate unless there are cardiopulmonary complications. Use ofpotassium supplements is not useful for prophylaxis againstfurther paralytic attacks and should not be given to patientsbetween attacks.

Journal of Thyroid Research 5

Nonspecific beta-adrenergic blockers like propranololhave also been proposed as an alternative treatment toameliorate the paralysis without rebound hyperkalemia andraise the serum levels of potassium and phosphate.High-doseoral propranolol (3-4mg/kg orally) alone has been reportedto rapidly abort the paralysis [45].

Propranolol, but not the selective beta1-blocker metopro-lol, also effectively prevented recurrence of paralytic attacksor inhibited paralysis induced by a carbohydrate load. At adose of 40mg four times a day, propranolol prevented paral-ysis in carbohydrate-inducedTPP in about two thirds of casesby inhibiting the activity of Na/K-ATPase [46]. Because TPPdoes not recur once the patient’s euthyroid adequate controlof hyperthyroidism is the mainstay of therapy. The cause forthe hyperthyroidism should be identified. Definitive treat-ment with radioactive iodine or thyroidectomy should begiven to patientswith hyperthyroidismdue toGraves’ disease,multinodular goiter, or toxic adenoma. Patients should avoidprecipitating factors including heavy carbohydrate intake,high-salt diet, alcohol ingestion, and undue exertion untilthyrotoxicosis is under control. The use of nonselective beta-blockers is important during early treatment with antithyroiddrugs or after radioactive iodine when a euthyroid statusis not yet achieved. In contrast to familial hypokalemic PP,carbonic anhydrase inhibitors have not been shown to be ofbenefit in thyrotoxic PP andmay even increase the frequencyof attacks [47].

7. Conclusion

TPP has to always be kept in mind while evaluating acase of hypokalemic paralysis. TPP has been increasinglydocumented in Asian and Hispanic populations in the USA.The subtleness of underlying hyperthyroidism often delaysdiagnosis. Biochemical hyperthyroidism with normal uri-nary potassium excretion and ECG changes clinches to dia-gnosis of TPP. Treatment with low-dose potassium supple-ments and nonselective beta-blockers should be initiatedupon diagnosis, and the serum potassium level should befrequently monitored to prevent rebound hyperkalemia.Increased awareness among physicians about this disorderwill result in early diagnosis, appropriate treatment, and theprevention of rebound hyperkalemia.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

References

[1] M. Rosenfeld, “Acute aufsteigende lahmung bei morbus base-dow,” Klin Wochenschr (Bed), vol. 39, pp. 538–540, 1902.

[2] S. Okinaka, K. Shizume, S. Iino et al., “The association ofperiodic paralysis and hyperthyroidism in Japan,” The Journalof Clinical Endocrinology &Metabolism, vol. 17, no. 12, pp. 1454–1459, 1957.

[3] K. P. Ober, “Thyrotoxic periodic paralysis in the United States.Report of 7 cases and review of the literature,”Medicine, vol. 71,no. 3, pp. 109–120, 1992.

[4] A. J. McFadzean and R. Yeung, “Periodic paralysis complicatingthyrotoxicosis in Chinese,” The British Medical Journal, vol. 1,no. 538, pp. 451–455, 1967.

[5] D. E. Kelley, H. Gharib, F. P. Kennedy, R. J. Duda Jr., and P.G. McManis, “Thyrotoxic periodic paralysis. Report of 10 casesand review of electromyographic findings,” Archives of InternalMedicine, vol. 149, no. 11, pp. 2597–2600, 1989.

[6] G. T. C. Ko, C. C. Chow, V. T. F. Yeung, H. H. L. Chan, J. K. Y. Li,and C. S. Cockram, “Thyrotoxic periodic paralysis in a Chinesepopulation,” QJM, vol. 89, no. 6, pp. 463–468, 1996.

[7] A. Chan, R. Shinde, C. C. Chow, C. S. Cockram, and R.Swaminathan, “In vivo and in vitro sodium pump activity insubjects with thyrotoxic periodic paralysis,”The British MedicalJournal, vol. 303, no. 6810, pp. 1096–1099, 1991.

[8] R. B. Layzer, “Periodic paralysis and the sodium-potassiumpump,” Annals of Neurology, vol. 11, no. 6, pp. 547–552, 1982.

[9] S. Soonthornpun, W. Setasuban, and A. Thamprasit, “Insulinresistance in subjects with a history of thyrotoxic periodicparalysis (TPP),” Clinical Endocrinology, vol. 70, no. 5, pp. 794–797, 2009.

[10] A. Chan, R. Shinde, C. C. Chow, C. S. Cockram, and R. Swami-nathan, “Hyperinsulinaemia and Na+, K+-ATPase activity inthyrotoxic periodic paralysis,” Clinical Endocrinology, vol. 41,no. 2, pp. 213–216, 1994.

[11] M. Guerra, A. Rodriguez del Castillo, E. Battaner, and M. Mas,“Androgens stimulate preoptic area Na+, K+-ATPase activity inmale rats,” Neuroscience Letters, vol. 78, no. 1, pp. 97–100, 1987.

[12] H. Biering, J. Bauditz, M. Pirlich, H. Lochs, and H. Gerl,“Manifestation of thyrotoxic periodic paralysis in two patientswith adrenal adenomas and hyperandrogenaemia,” HormoneResearch, vol. 59, no. 6, pp. 301–304, 2003.

[13] M. Frankenhaeuser, E. Dunne, and U. Lundberg, “Sex differ-ences in sympathetic adrenal medullary reactions induced bydifferent stressors,” Psychopharmacology, vol. 47, no. 1, pp. 1–5,1976.

[14] C. Schofl, C. Becker, K. Prank, A. von zur Muhlen, and G.Brabant, “Twenty-four-hour rhythms of plasma catecholaminesand their relation to cardiovascular parameters in healthy youngmen,”European Journal of Endocrinology, vol. 137, no. 6, pp. 675–683, 1997.

[15] K. Kjeldsen,M. E. Everts, and T. Clausen, “The effects of thyroidhormones on 3H-ouabain binding site concentration, Na,K-contents and 86Rb-efflux in rat skeletal muscle,” Pflugers Archiv,vol. 406, no. 5, pp. 529–535, 1986.

[16] A. Puwanant and R. L. Ruff, “INa and IKir are reduced in type1 hypokalemic and thyrotoxic periodic paralysis,” Muscle &Nerve, vol. 42, no. 3, pp. 315–327, 2010.

[17] R. L. Ruff, “Insulin acts in hypokalemic periodic paralysis byreducing inward rectifier K+ current,” Neurology, vol. 53, no. 7,pp. 1556–1563, 1999.

[18] D. P. Ryan, M. R. da Silva, T. W. Soong et al., “Mutationsin potassium channel Kir2.6 cause susceptibility to thyrotoxichypokalemic periodic paralysis,” Cell, vol. 140, no. 1, pp. 88–98,2010.


[19] C.-J. Cheng, S.-H. Lin, Y.-F. Lo et al., “Identification andfunctional characterization of Kir2.6 mutations associated withnon-familial hypokalemic periodic paralysis,” The Journal ofBiological Chemistry, vol. 286, no. 38, pp. 27425–27435, 2011.

[20] E. Matthews, R. Labrum, M. G. Sweeney et al., “Voltage sensorcharge loss accounts for most cases of hypokalemic periodicparalysis,” Neurology, vol. 72, no. 18, pp. 1544–1547, 2009.

[21] M.-J. Hsieh, R.-K. Lyu, W.-N. Chang et al., “Hypokalemic thy-rotoxic periodic paralysis: clinical characteristics and predictorsof recurrent paralytic attacks,” European Journal of Neurology,vol. 15, no. 6, pp. 559–564, 2008.

[22] S.-H. Lin, Y.-F. Lin, and M. L. Halperin, “Hypokalaemia andparalysis,” QJM, vol. 94, no. 3, pp. 133–139, 2001.

[23] Y.-C. Liu,W.-S. Tsai, T. Chau, and S.-H. Lin, “Acute hypercapnicrespiratory failure due to thyrotoxic periodic paralysis,” TheAmerican Journal of theMedical Sciences, vol. 327, no. 5, pp. 264–267, 2004.

[24] C.-C. Chang, C.-J. Cheng, C.-C. Sung et al., “A 10-year anal-ysis of thyrotoxic periodic paralysis in 135 patients: focuson symptomatology and precipitants,” European Journal ofEndocrinology, vol. 169, no. 5, pp. 529–536.

[25] W. Li, C. Changsheng, F. Jiangfang et al., “Effects of sex steroidhormones, thyroid hormone levels, and insulin regulation onthyrotoxic periodic paralysis in Chinese men,” Endocrine, vol.38, no. 3, pp. 386–390, 2010.

[26] J. I. Lee, T. S. Sohn, H. S. Son et al., “Thyrotoxic periodicparalysis presenting as polymorphic ventricular tachycardiainduced by painless thyroiditis,”Thyroid, vol. 19, no. 12, pp. 1433–1434, 2009.

[27] T. D. Tinker and J. B. Vannatta, “Thyrotoxic hypokalemicperiodic paralysis: report of four cases and review of theliterature,” Journal of the Oklahoma State Medical Association,vol. 80, no. 2, pp. 76–83, 1987.

[28] T. Tagami, T. Usui, A. Shimatsu, and M. Naruse, “Toxicthyroid adenomapresenting as hypokalemic periodic paralysis,”Endocrine Journal, vol. 54, no. 5, pp. 797–803, 2007.

[29] H. Ozaki, K. Mori, Y. Nakagawa, S. Hoshikawa, S. Ito, and K.Yoshida, “Autonomously functioning thyroid nodule associatedwith thyrotoxic periodic paralysis,” Endocrine Journal, vol. 55,no. 1, pp. 113–119, 2008.

[30] F.-S. Hsu, W.-S. Tsai, T. Chau, H.-H. Chen, Y.-C. Chen, and S.-H. Lin, “Thyrotropin-secreting pituitary adenoma presenting ashypokalemic periodic paralysis,” The American Journal of theMedical Sciences, vol. 325, no. 1, pp. 48–50, 2003.

[31] Y. Kiso, K. Yoshida, K. Kaise et al., “A case of thyrotropin (TSH)-secreting tumor complicated by periodic paralysis,” JapaneseJournal of Medicine, vol. 29, no. 4, pp. 399–404, 1990.

[32] M. J. Hannon, L. A. Behan, and A. Agha, “Thyrotoxic periodicparalysis due to excessive L-thyroxine replacement in a Cau-casian man,” Annals of Clinical Biochemistry, vol. 46, no. 5, pp.423–425, 2009.

[33] H.-K. Chou, Y.-T. Tsao, and S.-H. Lin, “An unusual causeof thyrotoxic periodic paralysis: triiodothyronine-containingweight reducing agents,” The American Journal of the MedicalSciences, vol. 337, no. 1, pp. 71–73, 2009.

[34] K. P. Ober and J. F. Hennessy, “Jodbasedow and thyrotoxicperiodic paralysis,” Archives of Internal Medicine, vol. 141, no.9, pp. 1225–1227, 1981.

[35] P. Piraino Neuenschwander, H. Pumarino Carte, F. BidegainGonzalez, M. L. Zura Jimenez, and F. Ferreiro Merino, “Thy-rotoxic hypokalemic periodic paralysis: 18 cases with differentforms of thyrotoxicosis,” Revista Clinica Espanola, vol. 195, no.5, pp. 294–297, 1995.

[36] S. T. Laroia, K. M. Zaw, A. K. Ganti, W. Newman, and A. O.Akinwande, “Amiodarone-induced thyrotoxicosis presenting ashypokalemic periodic paralysis,” Southern Medical Journal, vol.95, no. 11, pp. 1326–1328, 2002.

[37] S. Akar, A. Comlekci, M. Birlik et al., “Thyrotoxic periodicparalysis in a Turkish male; The recurrence of the attack afterradioiodine treatment,”Endocrine Journal, vol. 52, no. 1, pp. 149–151, 2005.

[38] J. Cohen-Lehman, M. M. Charitou, and I. Klein, “Tiratricol-induced periodic paralysis: a review of nutraceuticals affectingthyroid function,” Endocrine Practice, vol. 17, no. 4, pp. 610–615,2011.

[39] M. A. Manoukian, J. A. Foote, and L. M. Crapo, “Clinicaland metabolic features of thyrotoxic periodic paralysis in 24episodes,” Archives of Internal Medicine, vol. 159, no. 6, pp. 601–606, 1999.

[40] C. Boccalandro, L. Lopez, F. Boccalandro, and V. Lavis, “Elec-trocardiographic changes in thyrotoxic periodic paralysis,”TheAmerican Journal of Cardiology, vol. 91, no. 6, pp. 775–777, 2003.

[41] Y.-J. Hsu, Y.-F. Lin, T. Chau, J.-T. Liou, S.-W. Kuo, and S.-H. Lin, “Electrocardiographic manifestations in patients withthyrotoxic periodic paralysis,” The American Journal of theMedical Sciences, vol. 326, no. 3, pp. 128–132, 2003.

[42] K.-C. Lu, Y.-J. Hsu, J.-S. Chiu, Y.-D. Hsu, and S.-H. Lin,“Effects of potassium supplementation on the recovery of thy-rotoxic periodic paralysis,”The American Journal of EmergencyMedicine, vol. 22, no. 7, pp. 544–547, 2004.

[43] M. Cesur, F. Bayram, M. A. Temel et al., “Thyrotoxichypokalaemic periodic paralysis in a Turkish population: threenew case reports and analysis of the case series,” ClinicalEndocrinology, vol. 68, no. 1, pp. 143–152, 2008.

[44] H. Tassone, A. Moulin, and S. O. Henderson, “The pitfallsof potassium replacement in thyrotoxic periodic paralysis: acase report and review of the literature,” Journal of EmergencyMedicine, vol. 26, no. 2, pp. 157–161, 2004.

[45] S.-H. Lin and Y.-F. Lin, “Propranolol rapidly reverses paralysis,hypokalemia, and hypophosphatemia in thyrotoxic periodicparalysis,” American Journal of Kidney Diseases, vol. 37, no. 3,pp. 620–623, 2001.

[46] R. T. T. Yeung andT. F. Tse, “Thyrotoxic periodic paralysis: effectof propranolol,”TheAmerican Journal of Medicine, vol. 57, no. 4,pp. 584–590, 1974.

[47] L. Ptacek, “The familial periodic paralyses and nondystrophicmyotonias,” The American Journal of Medicine, vol. 105, no. 1,pp. 58–70, 1998.

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

review article thyrotoxic periodic paralysis: clinical...

Documents