Thyrotoxic Periodic Paralysis Research Articles

Thyrotoxic Periodic Paralysis: A Diagnostic Challenge

The aim of this article was to review the clinical presentation, pathogenesis, and management of thyrotoxic periodic paralysis (TPP). A MEDLINE search was conducted for articles published during the last 40 yr based on the key words thyrotoxic periodic paralysis and hypokalemic periodic paralysis. A total of 281 primary articles and 168 references of the retrieved articles were also reviewed. TPP is a common complication of hyperthyroidism in Asian men but is increasingly seen in Western countries. Hypokalemia and muscle paralysis results from a sudden intracellular shift of potassium and is not due to potassium deficiency. Clinical features of hyperthyroidism in patients with TPP may be subtle. Immediate potassium supplementation prevents serious cardiopulmonary complications and may hasten the recovery of muscle weakness. Nonselective beta-adrenergic blockers can ameliorate and prevent recurrence of the paralytic attacks. This episodic paralysis will remit with definitive control of hyperthyroidism. Increased sodium-potassium ATPase pump activity and enhanced insulin response in patients with TPP is postulated to contribute to the hypokalemia. The genetic predisposition for TPP is not entirely clear. Association of polymorphisms of the calcium channel alpha1-subunit gene with TPP has been noted. Due to population mobility, TPP is increasingly common in Western countries. Early diagnosis and prompt treatment prevent life-threatening complications associated with hypokalemia and muscle weakness. Assaying of thyroid function in patients with hypokalemic paralysis distinguishes TPP from other forms of hypokalemic periodic paralysis.

Thyrotoxic Periodic Paralysis

Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis. It has been increasingly reported in the USA due to the rise in the immigrant population. Hypokalemia in TPP results from an intracellular shift of potassium induced by the thyroid hormone sensitization of Na+/K+–ATPase rather than depletion of total body potassium. Treatment of TPP includes prevention of this shift of potassium by using nonselective beta-blockade, correcting the underlying hyperthyroid state, and replacing potassium. TPP is curable once a euthyroid state is achieved. It is important for physicians to distinguish TPP from familial hypokalemic periodic paralysis, a more common cause of periodic paralysis in Caucasians. The absence of a family history of paralysis, male sex, presentation in the second to fourth decades of life, and signs of thyrotoxicosis like sinus tachycardia help in the diagnosis of this disorder. Early recognition of TPP is vital to initiating appropriate treatment and to avoiding the risk of rebound hyperkalemia that may occur if high-dose potassium replacement is given.

Drug-Induced Thyrotoxic Periodic Paralysis

To report a case of iodine-induced (Jod-Basedow) hyperthyroidism leading to thyrotoxic periodic paralysis (TPP). A 64-year-old white male, one day status-post-cardiac catheterization, presented to the local emergency department with profound weakness of his extremities and an inability to stand on his own. Pertinent laboratory test results included a potassium level of 3.0 mEq/L. Treatments of oral and intravenous potassium supplementation resulted in his complete recovery. Two days later he was diagnosed with hyperthyroidism and subsequently treated with nadolol 40 mg daily and methimazole 20 mg daily. At time of writing, the patient remained euthyroid, receiving no antithyroid medications. There had been no further reports of paralysis in the 6 years since his original presentation. The Naranjo probability scale indicated a probable relationship between the patient's episode of TPP and his exposure to the iodinated contrast dye. TPP is an uncommon manifestation in white patients with hyperthyroidism. Iodine-induced TPP is even more rare, with only 2 such cases reported as of November 2, 2005. In this case, Jod-Basedow hyperthyroidism was induced by the iodine-containing dye that the patient received during cardiac catheterization. Soon after the dye was administered, he developed TPP. Clinicians should be aware not only of potential causes of drug-induced thyroid disease, but also of the potential for drug-induced hyperthyroidism leading to TPP. The diagnosis of TPP should be considered in patients presenting with acute onset of extremity weakness or paralysis and hypokalemia. Quick diagnosis and prompt treatment of TPP can prevent life-threatening complications of this treatable and curable disorder.

An Unusual Endocrine Cause of Recurrent Paraparesis

Endocrine causes of paraparesis are few and include thyrotoxic periodic paralysis, adrenomyeloneuropathy, acromegaly, primary hyperparathyroidism, and Paget disease. We report a middle-aged man who presented with recurrent paraparesis resulting from polyostotic Paget disease of the spine and well responded to alendronate therapy.

Thyrotoxic periodic paralysis and polymorphisms of sodium–potassium ATPase genes

Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism association with recurrent, reversible episodes of muscle weakness. Increased sodium-potassium ATPase (Na/K-ATPase) pump activity is postulated to contribute to the hypokalaemic paralytic attacks in TPP. The aim of this study was to determine the genetic predisposition to TPP in relation to Na/K-ATPase genes. A case-control association study. Ninety-nine male Chinese TPP patients were compared to 84 male Graves' disease (GD) patients without TPP and 100 normal male controls. A total of 1500 base pairs upstream of the transcriptional start site of the five Na/K-ATPase genes that are expressed in the skeletal muscles, namely ATP1A1, ATP1A2, ATP1B1, ATP1B2 and ATP1B4, were sequenced in all subjects for mutations or polymorphisms. The single nucleotide polymorphisms (SNPs) of the coding regions of the five genes were also studied for association with TPP. No mutations were detected in the 5' regions of the five genes in any of the patients studied. There was no difference in the distribution of SNPs and SNP haplotypes in the upstream and coding region of these genes between the three groups of subjects. No association between the polymorphisms of ATP1A1, ATP1A2, ATP1B1, ATP1B2 and ATP1B4 genes and TPP could be detected.

Mutation screening in Chinese hypokalemic periodic paralysis patients

Thyrotoxic periodic paralysis (TPP), familial periodic paralysis (FPP), and sporadic periodic paralysis (SPP) are the most common causes of hypokalemic periodic paralysis (hypoKPP). The patients present with similar clinical features characterized by episodic attacks of muscle weakness and a decrease in blood potassium. Mutations in the gene encoding the voltage-sensor coding regions of the skeletal muscle sodium channel gene ( SCN4A) and the α-1 subunit of the skeletal muscle calcium channel gene were analyzed in 23 Chinese hypoKPP patients, including 1 FPP pedigree, 14 TPP patients, and 8 SPP patients. In addition, R83H mutation of the potassium channel subunit gene which was originally published as periodic paralysis mutation was also analyzed. A heterozygous CGT-TGT mutation at codon 672 in SCN4A gene was identified to segregate with the disease in the FPP family. Mutations in these regions were excluded in those patients with SPP and TPP. The results suggest that a likely genetic basis for FPP does not contribute to TPP and SPP, despite close similarities among FPP, TPP, and SPP.

Ventricular Fibrillation Due to Severe Hypokalemia Induced by Steroid Treatment in a Patient with Thyrotoxic Periodic Paralysis

We report a 25-year-old Japanese man with ventricular fibrillation associated with severe hypokalemia. He developed arm and leg paralysis. He had received 2 g of methylprednisolone because thoracic epidural hematoma had been suspected in another hospital. His serum potassium was 0.8 mEq/l on arrival at our hospital. Half an hour after arrival ventricular fibrillation occurred. Treatment with electric defibrillation 8 times was successful. Afterward Graves' disease was diagnosed, therefore, his clinical symptom was diagnosed as thyrotoxic periodic paralysis. We considered that the unusual condition of hyperthyroid-related hypokalemia worsened by steroid therapy induced the ventricular fibrillation.

Thyrotoxic periodic paralysis: a case report

Thyrotoxic periodic paralysis (TPP) is characterized by recurrent episodes of muscle weakness and hypokalemia associated with thyroid hyperactivity. Reported predominantly among individuals of Asian descent, TPP is a rare manifestation of hyperthyroidism in western populations. We describe a typical case of TPP in a 33-year-old portuguese male, who presented with acute tetraparesis associated with hypokalemia (K+ 2.6 mEq/L). The patient had a 8-week history of several episodes of paraparesis of variable intensity; these attacks were usually nocturnal, preceded by strenuous exercise and resolved spontaneously after a few hours. The presence of tachycardia, weight loss, and goiter led to the diagnosis of Graves's disease. The correction of the hyperthyroid function with metimazol and propranolol prevented further episodes of muscle weakness. Thyrotoxic periodic paralysis should be considered in the differential diagnosis of acute episodes of motor paralysis in young patients. The maintenance of a euthyroid status is an essential part of management as this prevents the paralytic episodes.

Arg16Gly polymorphism in β2‐adrenergic receptor gene is not associated with thyrotoxic periodic paralysis in Korean male patients with Graves’ disease

Thyrotoxic periodic paralysis (TPP) occurs most frequently in Asian males and present with an acute episode of proximal muscle weakness in the setting of thyrotoxicosis. Despite the fact that mutations were described in genes encoding ion channels in familial hypokalaemic periodic paralysis, no definite genetic variants were found in TPP. beta2-adrenergic receptors (ADRB2s) are expressed in skeletal muscle and stimulate the sodium pump. Single nucleotide polymorphisms in ADRB2 gene were identified and may act as disease modifiers in various diseases. We were to demonstrate that ADRB2 gene might be a susceptibility gene for TPP in Korean male patients with Graves' disease. In a series of 28 male TPP patients and 31 control patients, three polymorphisms in ADRB2 gene have been studied: a T to C substitution at -47 (-47T/C), Arg16Gly and Gln27Glu. Control patients were male Graves' patients without history of paralysis. The distributions of the -47C, Gly16 and Glu27 alleles in all patients were 0.02, 0.34 and 0.02, respectively. The genotype Arg16/Arg16 was not significantly associated with TPP (odds ratio 0.53; 95% confidence interval, 0.19-1.50; corrected P = 0.897). Also, the frequency of genotype Gly16/Gly16 was not significantly different in TPP patients than in controls (0.07 vs. 0.23; odds ratio, 0.26; 95% confidence interval, 0.05-1.40; corrected P = 0.45). Allele frequencies of ADRB2 in patients with TPP did not differ from controls. The polymorphism of the ADRB2 gene may not confer genetic susceptibility to TPP in Korean male patients with Graves' disease.

Abstract #794: Thyrotoxic Hypokalemic Periodic Paralysis in a White Man: Case Report and Review of the Literature

Abstract #794: Thyrotoxic Hypokalemic Periodic Paralysis in a White Man: Case Report and Review of the Literature

Acute generalized weakness due to thyrotoxic periodic paralysis

THE CASE: A 28-year-old First Nations man was transferred from a northern nursing station to the Health Sciences Centre in Winnipeg for investigation of a 1-day history of generalized weakness that began when he woke in the early morning. He had no fever, myalgia, or gastrointestinal, respiratory or

Skeletal Muscle Dihydropyridine-Sensitive Calcium Channel (CACNA1S) Gene Mutations in Chinese Patients with Hypokalemic Periodic Paralysis

Thyrotoxic periodic paralysis (TPP), familial periodic paralysis (FPP), and sporadic periodic paralysis (SPP) are common causes of hypokalemic periodic paralysis and have similar clinical presentations, thus possibly sharing the identical mutations. We analyzed the role of the three known CACNA1S gene mutations (R528H, R1239H, and R1239G) in Chinese patients, including two FPP families, 36 TPP patients, 12 SPP patients, and their relatives. Fifty unrelated healthy subjects were also studied. Genomic DNA was prepared from the peripheral blood of all patients, their family members, and healthy subjects. Mutations of the CACNA1S gene were screened using polymerase chain reaction-based restriction analysis. Two FPP families had the R528H point mutation, but with incomplete penetrance occurring more commonly in men than in women. Only one SPP patient had a de novo mutation (R528H). None of the TPP patients had mutations in the three hot spots. Patients with FPP have R528H mutations in the CACNA1S gene. Only a few patients with SPP may share similar mutations with FPP. TPP patients do not carry any of the three known gene mutations.

Thyroid disease in the emergency department: A clinical and laboratory review

Emergency physicians regularly treat patients with thyroid disorders. Until the 1950s, clinical evaluation was the only available diagnostic tool. Since then, increasingly sophisticated laboratory assays have been developed to confirm thyroid pathology. Thyroid physiology, fundamental to interpreting thyroid function tests, is based on a classic negative feedback mechanism involving the hypothalamic-pituitary-thyroid axis. Primary hypothyroidism in developed countries is most commonly caused by Hashimoto’s disease. Secondary and tertiary etiologies are uncommon and the result of hypothalamic and pituitary pathology. Clinical presentations range from subclinical disease to myxedema coma. Thyrotoxicosis has many etiologies. A hyperadrenergic state precipitates characteristic signs and symptoms. Thyroid storm and thyrotoxic periodic paralysis are emergent complications. Third generation assays have made thyroid function testing practical for emergency physicians. An ultrasensitive thyroid stimulating hormone level is the most useful. A free thyroxine level is the preferred study for confirming a thyroid disorder. Confounding factors may affect thyroid function interpretation.

Thyrotoxic Periodic Paralysis in a Turkish Male; The Recurrence of the Attack after Radioiodine Treatment

Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare complication of hyperthyroidism and an uncommon form of hypokalemic periodic paralysis. Its differentiation of more common forms of periodic paralysis is important because aggressive treatment can place the patient at risk for rebound hyperkalemia. Treatment of the underlying thyroid dysfunction cures the muscle symptoms. Here we describe a 37-year-old Turkish male with THPP whose paralysis attack recurred soon after administration of radioactive iodine.

Thyrotoxic Hypokalemic Periodic Paralysis in a Turkish Male with Graves' Disease: A Rare Case Report and Review of the Literature

Thyrotoxic hypokalemic periodic paralysis (THPP) is a very rare complication of thyrotoxicosis in whites, but is more frequently reported in individuals of Asian descent. Hypokalemia, with associated flaccid paralysis, and signs of hyperthyroidism, are the hallmark. We have reported a case of a 28-yr-old white man with Graves' disease presenting with a 2-wk history of episodic flaccid quadriplegia. Physical examination disclosed a resting tachycardia and symmetrical, proximal weakness involving both arms and legs. Electrocardiogram and electrolyte analysis showed a severe hypokalemia, and thyroid function tests revealed hyperthyroidism. The patient was diagnosed as having Graves' hyperthyroidism and THPP. Paralysis resolved with potassium supplements. He was treated with propranolol and, subsequently, methimazole. He had no further episodes of hypokalemic paralysis. To the best of the author's knowledge, and after a Medline search, THPP has not been described previously in a Turkish man.

Thyrotoxic Periodic Paralysis

Thyrotoxic periodic paralysis (TPP), a hyperthyroidism-related hypokalemia and muscle-weakening condition resulting from a sudden shift of potassium into cells, has been seen increasingly in Western countries. Failure to recognize TPP may lead to improper management. Many patients with TPP have no obvious symptoms related to hyperthyroidism. Therefore, several important clues may help in diagnosing and managing TPP: presentation in an adult male with no family history of periodic paralysis; presence of systolic hypertension, tachycardia, high QRS voltage, first-degree atrioventricular block on electrocardiography; presence of low-amplitude electrical compound muscle action potential on electromyography and no notable changes in amplitudes after low doses of epinephrinine; and typical acid-base and electrolyte findings such as normal blood acid-base state, hypokalemia with low urinary potassium excretion, hypophosphatemia associated with hypophosphaturia, and hypercalciuria. Immediate therapy with potassium chloride supplementation may foster a rapid recovery of muscle strength, but with a risk of rebound hyperkalemia. Nonselective beta-blockers may provide an alternative choice. Long-term therapy with definite control of hyperthyroidism completely abolishes attacks. Early diagnosis and prompt treatment of TPP prevent life-threatening complications of this treatable and curable disorder.

PII: S1098-3597(05)80060-2

Emergency physicians regularly treat patients with thyroid disorders. Until the 1950s, clinical evaluation was the only available diagnostic tool. Since then, increasingly sophisticated laboratory assays have been developed to confirm thyroid pathology. Thyroid physiology, fundamental to interpreting thyroid function tests, is based on a classic negative feedback mechanism involving the hypothalamic-pituitary-thyroid axis. Primary hypothyroidism in developed countries is most commonly caused by Hashimoto’s disease. Secondary and tertiary etiologies are uncommon and the result of hypothalamic and pituitary pathology. Clinical presentations range from subclinical disease to myxedema coma. Thyrotoxicosis has many etiologies. A hyperadrenergic state precipitates characteristic signs and symptoms. Thyroid storm and thyrotoxic periodic paralysis are emergent complications. Third generation assays have made thyroid function testing practical for emergency physicians. An ultrasensitive thyroid stimulating hormone level is the most useful. A free thyroxine level is the preferred study for confirming a thyroid disorder. Confounding factors may affect thyroid function interpretation.

Paralisia periódica hipocalêmica tireotóxica: relato de 3 casos

Paralisia Periódica Hipocalêmica Tireotóxica (PPHT) é uma complicação rara do hipertireoidismo, mais freqüente em orientais que brancos. Apresentamos três pacientes do sexo masculino, brasileiros, cujas idades eram de 28 anos (caso 1), 29 anos (caso 2) e 60 anos (caso 3) com diagnóstico de PPHT. Foram admitidos com tetraparesia das extremidades, tendo o caso 1 relatado crises recorrentes de paralisia e os casos 2 e 3, apenas um episódio. No caso 1, estavam presentes sinais e sintomas de hipertireoidismo como emagrecimento, sudorese, tremor de extremidades, palpitação e bócio difuso discreto, enquanto no caso 2 manifestou-se apenas oftalmopatia, e o terceiro paciente referia diagnóstico de fibrilação atrial pregressa sem avaliação da função tireoidiana. Exames laboratoriais mostraram hipocalemia, TSH suprimido e T4 livre elevado em todos os pacientes. Foram tratados com potássio intravenoso, propranolol e tiamazol via oral, com remissão dos sintomas. O relato dos casos destaca a freqüente dificuldade diagnóstica desta enfermidade que apresenta evolução favorável quando diagnosticada e tratada adequadamente.

Effects of potassium supplementation on the recovery of thyrotoxic periodic paralysis

Potassium supplements have been recommended to hasten recovery and prevent cardiopulmonary complications in patients with thyrotoxic periodic paralysis (TPP). However, this recommendation has not yet been proven efficacious. Thirty-two patients with acute attacks of TPP over a 3-year-period were divided into 2 groups. Group A (n = 12) was a control group treated with normal saline infusion 125 mL/hr only. Group B (n = 20) received intravenous KCl administration at a rate of 10 mmol/hr in normal saline 125 mL/hr. During the attack and for 6 hours after muscle recovery, hemodynamics were continuously recorded and muscle strength and plasma K + concentration were measured hourly. The sex, age, muscle strength, thyroid function, biochemical values including plasma K + levels, as well as the time from attack to therapy (3.6 ± 1.6 v 3.3 ± 1.0 hr) were not significant between the 2 groups. However, recovery time was significantly shorter in the KCl group than the control (6.3 ± 3.8 v 13.5 ± 7.5 hr, P < .01). Rebound hyperkalemia greater than 5.5 mmol/L occurred in 40% patients receiving KCl. The dose of KCl administered and peak K + concentration were positively correlated (r = 0.85, P < .001). In conclusion, KCl therapy proves to help the recovery of paralysis in TPP associated with rebound hyperkalemia. KCl supplementation should be given as small as possible (<10 mmol/hr) to avoid rebound hyperkalemia unless there are cardiopulmonary complications.

Thyrotoxic periodic paralysis: an overview

SUMMARYThyrotoxic periodic paralysis (TPP) is a fairly common manifestation of hyperthyroidism in Asian populations, with an incidence of about 1.9% in thyrotoxic patients, but it is rarely diagnosed among Caucasians and blacks in the Western world. The diagnosis often can be made on the basis of the clinical manifestations alone. Sometimes, periodic paralysis precedes hyperthyroidism or occurs in silent hyperthyroidism. As a result, physicians may easily overlook it even when life-threatening hypokalemia is present. The pathophysiology of this disorder is still not well understood. Correction of the thyrotoxic state is the definitive treatment. Potassium supplementation, propranolol, and spironolactone may be helpful both in the acute state and in preventing attacks.