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Recognizing the underlying causes of hypokalemic paralysis seems to be essential for the appropriate management of affected patients and their prevention of recurrent attacks. There is, however, a paucity of documented reports on the etiology of hypokalemic paralysis in Korea. We retrospectively analyzed 34 patients with acute flaccid weakness due to hypokalaemia who were admitted during the 5-year study period in order to determine the spectrum of hypokalemic paralysis in Korea and to identify the differences in clinical parameters all across the causes of hypokalemic paralysis. We divided those 34 patients into 3 groups; the 1st group, idiopathic hypokalemic periodic paralysis (HPP), the 2nd, thyrotoxic periodic paralysis (TPP), and the 3rd group, secondary hypokalemic paralysis (HP) without TPP. Seven of the patients (20.6%) were diagnosed as idiopathic HPP considered the sporadic form, and 27 patients (79.4%) as secondary HP. Among the patients diagnosed as secondary HP, 16 patients (47.1%) had TPP. Patients of secondary hypokalemic paralysis without TPP required a longer recovery time compared with those who had either idiopathic HPP or TPP. This is due to the fact that patients of secondary HP had a significantly negative total body potassium balance, whereas idiopathic HPP and TPP were only associated with intracellular shift of potassium. Most of the TPP patients included in our study had overt thyrotoxicosis while 3 patients had subclinical thyrotoxicosis. This study shows that TPP is the most common cause of hypokalemic paralysis in Korea. And we suggest that doctors should consider the presence of TPP in patients of hypokalemic paralysis even if they clinically appear to be euthyroid state.

SUMMARY

Thyrotoxic hypokalemic periodic paralysis (TPP) is characterized by acute attacks of weakness, hypokalemia, and thyrotoxicosis of various etiologies. These transient attacks resemble those of patients with familial hypokalemic periodic paralysis (hypoKPP) and resolve with treatment of the underlying hyperthyroidism. Because of the phenotypic similarity of these conditions, we hypothesized that TPP might also be a channelopathy. While sequencing candidate genes, we identified a previously unreported gene (not present in human sequence databases) that encodes an inwardly rectifying potassium (Kir) channel, Kir2.6. This channel, nearly identical to Kir2.2, is expressed in skeletal muscle and is transcriptionally regulated by thyroid hormone. Expression of Kir2.6 in mammalian cells revealed normal Kir currents in whole-cell and single-channel recordings. Kir2.6 mutations were present in up to 33% of the unrelated TPP patients in our collection. Some of these mutations clearly alter a variety of Kir2.6 properties, all altering muscle membrane excitability leading to paralysis.

Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. All ethnicities can be affected, but TPP typically presents in men of Asian descent. The most common cause of TPP in thyrotoxicosis is Graves' disease. However, TPP can occur with any form of thyrotoxicosis. Up to our knowledge, very few cases ever reported the relationship between TPP and painless thyroiditis. We herein report a 25-yr-old Korean man who suffered from flaccid paralysis of the lower extremities and numbness of hands. The patient was subsequently diagnosed as having TPP associated with transient thyrotoxicosis due to painless thyroiditis. The paralytic attack did not recur after improving the thyroid function. Therefore, it is necessary that early diagnosis of TPP due to transient thyrotoxicosis is made to administer definite treatment and prevent recurrent paralysis.

Objectives. To describe 2 cases of thyrotoxic periodic paralysis. Methods. We report of 2 cases of thyrotoxic periodic paralysis in 2 individuals from 2 different backgrounds with emphasis on their presentation and treatment. We also conducted a literature search to put together an update review of thyrotoxic periodic paralysis. Results. A 47-year-old Chinese and 28-year-old Caucasian male presented with profound yet reversible weakness associated with hypokalemia on admission bloods and thyrotoxicosis. Both were given definitive therapy to prevent recurrence of attacks with any future relapse of thyrotoxicosis. Conclusion. Thyrotoxic periodic paralysis (TPP) is a rare but potentially serious complication of thyrotoxicosis resulting in temporary but severe muscle weakness. Recent discovery of a novel mutation in the KCNJ18 gene which codes for an inwardly rectifying potassium channel and is controlled by thyroid hormones may provide greater insight into the pathogenesis of TPP.

Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare, potentially life-threatening endocrine emergency. It is characterized by recurrent muscle weakness and hypokalemia. Because many THPP patients do not have obvious symptoms and signs of hyperthyroidism, misdiagnosis may occur. The published studies revealed that definitive therapy for THPP is control of hyperthyroidism by medical therapy, radioactive iodine or surgery, but the long-term post-operative follow-up result was not observed. We reported two cases of medically refractory THPP with recurrent paralysis of extremities and hypokalemia, and both were combined with thyroid nodules. Both patients were treated with total thyroidectomy; the pathology revealed that one is Graves' disease with thyroid papillary carcinoma, and the other is adenomatous goiter with papillary hyperplasia. No episode of periodic paralysis was noted and laboratory evaluation revealed normal potassium level during the post-operative follow up. Our experience suggests that total thyroidectomy by experienced surgeon is an appropriate and definite treatment for medically refractory THPP, especially in cases combined with thyroid nodules.

Thyrotoxic periodic paralysis (TPP) attacks are characterized as recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. Episodes of weakness are accompanied by hypokalemia, which left untreated can lead to life-threatening arrhythmias (6). In this case study, we followed a patient’s potassium levels analyzing how they correlate with electrocardiogram changes seen while treating his hypokalemia and ultimately his paralysis.

A 21-year-old Caucasian man had recurrent hospital admissions for thyrotoxic periodic paralysis (TPP). He was poorly compliant with carbimazole treatment and admitted to recreational ecstasy use the night prior to each admission. This is the first time that ecstasy has been identified as a precipitant of TPP.

Hyperthyroidism may be associated with hypokalemic periodic paralysis. Two cases are presented demonstrating intermittent attacks of flaccid paralysis associated with clinical symptoms, signs and laboratory findings of hyperthyroidism. During an attack, one patient had a serum potassium of 2.1 mEq. per litre.

Various factors such as trauma, exposure to cold, excessive carbohydrate ingestion and certain medications have been stated to precipitate an episode of paralysis. Attacks may range from mild weakness to generalized flaccid paralysis with loss of deep tendon reflexes. Several reported patients have died owing to cardiac arrest or respiratory paralysis.

During attacks, the serum potassium is usually in the range of 2.2 to 3.2 mEq. per litre. It is postulated that a metabolic abnormality affecting the muscle-cell membrane can occur in the hyperthyroid state resulting in a shift of potassium to the intracellular position, thus producing a situation of hyperpolarization of the muscle-cell membrane which in turn alters the muscle contractibility.

The importance of recognizing the unusual association of hypokalemic periodic paralysis with hyperthyroidism is stressed because, with successful treatment of the hyperthyroidism, the episodes of paralysis disappear.

This article aims at highlighting the importance of suspecting thyrotoxicosis in cases of recurrent periodic flaccid paralysis; especially in Asian men to facilitate early diagnosis of the former condition. A case report of a 28 year old male patient with recurrent periodic flaccid paralysis has been presented. Hypokalemia secondary to thyrotoxicosis was diagnosed as the cause of the paralysis. The patient was given oral potassium intervention over 24 hours. The patient showed complete recovery after the medical intervention and was discharged after 24 hours with no residual paralysis. Thyrotoxic periodic paralysis (TPP) is a complication of thyrotoxicosis, more common amongst males in Asia. It presents as acute flaccid paralysis in a case of hyperthyroidism with associated hypokalemia. The features of thyrotoxicosis may be subtle or absent. Thus, in cases of recurrent or acute flaccid muscle paralysis, it is important to consider thyrotoxicosis as one of the possible causes, and take measures accordingly.

Background

Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine.

Patients and Methods

Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1–2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined.

Results

Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2–24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations.

Conclusions

IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.

Methods: Seven male patients were enlisted who presented to the emergency department over a period of three years with weakness and paralysis in the morning.

Results: Initial electrolyte studies revealed hypokalaemia in these patients, and later thyroid function tests confirmed thyrotoxicosis for all. Only two of these patients had clinical symptoms and signs of thyrotoxicosis, the others being asymptomatic.

Conclusions: Early morning paralysis can be the first manifestation of hyperthyroidism in Asian men, without the other more typical symptoms of weight loss, increased appetite, excitability, sweaty palms or goitre. Treatment to a euthyroid state will ameliorate the syndrome.

We report a case of a Hispanic male presenting with acute onset of bilateral lower extremity weakness, without any antecedent viral or bacterial illness, dietary changes, infiltrative orbitopathy, diffuse goiter, infiltrative dermopathy, and family history of periodic paralysis, who was later found to have Graves' disease. This demonstrates a rare case of periodic paralysis as the initial presentation of hyperthyroidism. Thyrotoxic hypokalemic periodic paralysis is common in Asian and Hispanic individuals and uncommon in whites and African Americans.

A case is presented of a rare complication of hyperthyroidism, known as thyrotoxic hypokalaemic periodic paralysis, in a man from Nepal. A 26-year-old Nepalese man, with known hypokalaemia, was referred to the clinical laboratory services for electrolyte analysis. Results showed Na+ 120 mmol/l and K+ 2.8 mmol/l, and he was prescribed potassium chloride. In fact, he had previously been receiving potassium supplementation periodically and his history revealed that he had experienced the same type of attack and was hospitalised 6 months earlier. He had profound tremor and was agitated and irritable during his visit to this hospital. Thyroid function testing showed high T3 (tri-iodothyronine) and T4 (thyroxine) with low thyroid stimulating hormone (TSH) concentration in the serum, indicating thyrotoxic hypokalaemic periodic paralysis. Treatment with neomercazole resulted in an improvement during the follow up visit. Hypokalaemia is believed to be a consequence of a massive shift due to increased sodium–potassium–adenosine triphosphatase (Na+K+ATPase ) pump activity in the presence of elevated thyroid hormones.

Hypokalemic Periodic Paralysis is one form of Periodic Paralysis, a rare group of disorders that can cause of sudden onset weakness. A case of a 29 year old male is presented here. The patient presented with sudden onset paralysis of his extremities. Laboratory evaluation revealed a markedly low potassium level. The patient's paralysis resolved upon repletion of his low potassium and he was discharged with no neurologic deficits. An association with thyroid disease is well established and further workup revealed Grave's disease in this patient. Although rare, Periodic Paralysis must differentiated from other causes of weakness and paralysis so that the proper treatment can be initiated quickly.

Thyrotoxic periodic paralysis is a disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state. Thyrotoxic periodic paralysis is a common complication of hyperthyroidism in Asian populations, but can affect other ethnic groups as well. Due to population mobility, Thyrotoxic periodic paralysis is increasingly common in Western countries. Early diagnosis and prompt treatment of the thyrotoxic state and potassium supplementation prevent life-threatening complications associated with hypokalemia and muscle weakness. We present a young Turkish man who developed acute flaccid paralysis after receiving pulse prednisolone therapy for treatment of Pityriasis versicolor. His muscle strength and serum potassium fully recovered after potassium replacement and treatment of the thyrotoxic state which was a consequence of underlying Graves’ disease.

Evidence suggests that most hyperthyroid patients have a proximal myopathy. The more severe this is the more frequently are distal muscles, and ultimately, bulbar muscles involved. Probably acute thyrotoxic myopathy or encephalopathy supervenes on a previous chronic background or occurs concurrently with skeletal muscle involvement. Using careful electromyographic techniques evidence of myopathy may be found in most thyrotoxics; it disappears with adequate treatment of the primary disease.

Myasthenia gravis and periodic paralysis are also associated with thyrotoxicosis and their differentiation is discussed. Infiltrative ophthalmopathy is not related to the effects of excess thyroid hormone, but is possibly due to EPS working in conjunction with LATS.

Images

A thyrotoxic patient who initially presented with periodic paralysis is described. Precipitation of an attack by a high carbohydrate diet was associated with only a modest fall in plasma potassium but with a marked rise in total blood cell potassium.

Methods: 22 subjects were studied from two families with HPP caused by R528H mutation, four patients with thyrotoxic periodic paralysis, 15 normal controls, and four controls with hyperthyroidism. All family members were submitted to clinical evaluation, electrophysiological exercise testing, and DNA analysis. Patients with thyrotoxic periodic paralysis had exercise tests before and after treatment of their hyperthyroidism.

Results: Abnormal responses to the exercise tests were obtained only in subjects with recent attacks of weakness. They were not correlated with genotype, as asymptomatic carriers were unaffected. Patients with thyrotoxic periodic paralysis showed pronounced impairment while they were hyperthyroid, but improved when they were euthyroid. One patient with HPP and chronic KCl use had an increase in amplitude potentials over ~20 minutes, possibly related to alteration of potassium homeostasis.

Conclusions: The exercise test is a useful diagnostic test for periodic paralysis, but in the absence of recent weakness negative results must be viewed with caution. It has advantages over the DNA test in being a non-invasive functional test that can provide insights into abnormalities of muscle excitability.

Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene SCN4A, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications.

Thyrotoxic induced hypokalemic periodic paralysis is a rare disorder that had been described in middle-aged men, predominantly Asians and Hispanics. This case presented with generalized weakness and hypokalemia after changing prescription for levothyroxine and starting prednisone to treat upper respiratory infection in a previously asymptomatic middle-aged Hispanic male. In this paper, we will go over the clinical presentation, mechanisms, and treatment of thyrotoxic induced hypokalemic periodic paralysis. Our objectives are to identify the classic constellation of findings in thyrotoxic periodic paralysis and to recognize the importance of considering thyrotoxic periodic paralysis among patients with hypokalemia.

We present a case of fatal rebound hyperkalemia in a patient with thyrotoxic periodic paralysis (TPP) treated with potassium supplementation. Although TPP is a rare hyperthyroidism-related endocrine disorder seen predominantly in men of Asian origin, the diagnosis should be considered in patients of non-Asian origins presenting with hypokalemia, muscle weakness or acute paralysis. The condition may present as a life threatening emergency and unfamiliarity with the disease could result in a fatal outcome. Immediate therapy with potassium chloride supplementation may foster a rapid recovery of muscle strength and prevent cardiac arrhythmias secondary to hypokalemia, but with a risk of rebound hyperkalemia.

Over a 5-year period, three cases of thyrotoxic pretibial myxoedema were encountered. The incidence of pretibial myxoedema in Chinese thyrotoxic patients in Singapore was 0·7% (0·3% in females and 1·6% in males). One of the three patients also had thyroid acropachy. The incidence of thyrotoxic pretibial myxoedema in Singapore is compared with that in the literature and the aetiology briefly reviewed.

Management considerations in hypokalemic periodic paralysis include accurate diagnosis, potassium dosage for acute attacks, choice of diuretic for prophylaxis, identification of triggers, creating a safe physical environment, peri-operative measures, and issues in pregnancy. A positive genetic test in the context of symptoms is the gold standard for diagnosis. Potassium chloride is the favored potassium salt given at 0.5–1.0 mEq/kg for acute attacks. The oral route is favored, but if necessary, a mannitol solvent can be used for intravenous administration. Avoidance of or potassium prophylaxis for common triggers, such as rest after exercise, high carbohydrate meals, and sodium, can prevent attacks. Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. Potassium, water, and a telephone should always be at a patient's bedside, regardless of the presence of weakness. Perioperatively, the patient's clinical status should be checked frequently. Firm data on the management of periodic paralysis during pregnancy is lacking. Patient support can be found at .

Background and Purpose

Mutations of the skeletal muscle sodium channel gene SCN4A, which is located on chromosome 17q23-25, are associated with various neuromuscular disorders that are labeled collectively as skeletal muscle sodium channelopathy. These disorders include hyperkalemic periodic paralysis (HYPP), hypokalemic periodic paralysis, paramyotonia congenita (PMC), potassium-aggravated myotonia, and congenital myasthenic syndrome. This study analyzed the clinical and mutational spectra of skeletal muscle sodium channelopathy in Korean subjects.

Methods

Six unrelated Korean patients with periodic paralysis or nondystrophic myotonia associated with SCN4A mutations were included in the study. For the mutational analysis of SCN4A, we performed a full sequence analysis of the gene using the patients' DNA. We also analyzed the patients' clinical history, physical findings, laboratory tests, and responses to treatment.

Results

We identified four different mutations (one of which was novel) in all of the patients examined. The novel heterozygous missense mutation, p.R225W, was found in one patient with mild nonpainful myotonia. Our patients exhibited various clinical phenotypes: pure myotonia in four, and PMC in one, and HYPP in one. The four patients with pure myotonia were initially diagnosed as having myotonia congenita (MC), but a previous analysis revealed no CLCN1 mutation.

Conclusions

Clinical differentiating between sodium-channel myotonia (SCM) and MC is not easy, and it is suggested that a mutational analysis of both SCN4A and CLCN1 is essential for the differential diagnosis of SCM and MC.

Myotonic syndromes and periodic paralyses are rare disorders of skeletal muscle characterized mainly by muscle stiffness or episodic attacks of weakness. Familial forms are caused by mutation in genes coding for skeletal muscle voltage ionic channels. Familial periodic paralysis and nondystrophic myotonias are disorders of skeletal muscle excitability caused by mutations in genes coding for voltage-gated ion channels. These diseases are characterized by episodic failure of motor activity due to muscle weakness (paralysis) or stiffness (myotonia). Clinical studies have identified two forms of periodic paralyses: hypokalemic periodic paralysis (hypoKPP) and hyperkalemic periodic paralysis (hyperKPP), based on changes in serum potassium levels during the attacks, and three distinct forms of myotonias: paramyotonia congenita (PC), potassium-aggravated myotonia (PAM), and myotonia congenita (MC). PC and PAM have been linked to missense mutations in the SCN4A gene, which encodes α subunit of the voltage-gated sodium channel, whereas MC is caused by mutations in the chloride channel gene (CLCN1). Exercise is known to trigger, aggravate, or relieve symptoms. Therefore, exercise can be used as a functional test in electromyography to improve the diagnosis of these muscle disorders. Abnormal changes in the compound muscle action potential can be disclosed using different exercise tests. Five electromyographic (EMG) patterns (I-V) that may be used in clinical practice as guides for molecular diagnosis are discussed.