Thyrotoxic periodic paralysis in Chinese patients: milder thyrotoxicosis yet lower dose of (131)I should be avoided.

PURPOSE: Thyrotoxic periodic paralysis (TPP) is a complication of thyrotoxicosis mainly observed in male Asian patients. It was proposed that patients with TPP tend to have lower thyroid hormone levels. We aimed to prove this observation and to assess whether a lower I dose is feasible for prompt control of TPP. METHODS: A total of 123 male TPP patients were enrolled in this study in a 7-year period. Baseline characteristics were compared with 70 thyrotoxic patients without periodic paralysis (nTPP). Different I doses were given to 90 TPP patients with a median follow-up of 11 months, and the outcome was evaluated. RESULTS: The serum thyroid hormone levels, including total T3 and T4, and free T3 and T4, in TPP patients were slightly less elevated compared with those in nTPP patients. Patients who received lower radioactivity of I had an unsatisfactory overall remission rate of 28.6%. Longer time to remission (P = 0.004; hazard ratio, 1.846; 95% confidence interval, 1.216-2.798) was also observed in patients with lower dose. CONCLUSIONS: The serum thyroid hormone levels of TPP patients are lower than those of nTPP patients. Median/high dose of I is necessary to achieve rapid control of thyrotoxicosis.

Episodes of paralysis in Chinese men with thyrotoxic periodic paralysis are associated with elevated serum testosterone.

BACKGROUND: The strong predilection for thyrotoxic periodic paralysis (TPP) to occur in males suggests androgen may contribute to its pathogenesis. We therefore sought to determine if serum total and free testosterone (TT and FT) concentrations differed among patients with TPP during episodes of paralysis, patients with TPP between episodes of paralysis, and patients with Graves' disease (GD) not having TPP. METHODS: A total of 105 Chinese men were included in the study, and were divided into three groups. Group 1 consisted of men with TPP who were studied during episodes of paralysis; group 2 consisted of men with TPP who were studied between episodes of paralysis; group 3 consisted of men with GD not having TPP. Patients in each were different persons. Serum electrolytes, free triiodothyronine (FT3), free thyroxine (FT4), TT, and FT were measured. Multiple regression analyses and analysis of covariance were performed to analyze the relationship of serum parameters, group status, and age. RESULTS: One multiple regression analysis was used to determine if serum TT concentrations were associated with age, FT3, FT4, or group status. This analysis indicated that age, FT4 level, and group status were significantly and independently associated with serum TT concentrations. With regard to group status, patients in group 1 had serum TT concentrations 0.92 ng/mL higher than patients in group 3 (p=0.033). As to FT4 level, TT concentrations increased by 0.016 ng/mL for each additional pmol/L of FT4 (p=0.002). Another multiple regression analysis was used to determine if serum FT concentrations were associated with age, FT3, FT4, group status, or serum TT concentrations. This analysis revealed that serum TT concentrations and group status were significantly and independently associated with serum FT concentrations. In terms of group status, patients in group 1 had serum FT concentrations of 2.11 pg/mL greater on average than patients in group 3 (p=0.006). CONCLUSIONS: We infer that episodes of paralysis in Chinese men with TPP are associated with elevated serum testosterone. We also found serum TT and FT concentrations of men with GD are both affected by group status; serum TT rather than FT concentrations are associated with thyroid function.

Clinical profile of periodic paralysis.

This cross sectional descriptive study was done to find out common clinical presentations, etiologies and laboratory investigation abnormalities in patients of periodic paralysis. Study was carried out in 30 patients with an age range from 8 to 70 years who were enrolled from July 2008 to June 2009 in Mymensingh Medical College Hospital (MMCH) medicine unit. Individuals who were admitted with sudden onset generalized muscle weakness, had history of previous attack and serum potassium level <3mmol/l or >5.5mmol/l were included in this study. In this series, majority of the patients were male (66.67%). Male: female ratio was approximately 2:1. The mean age of the patients was 27.4±4.5 years. Majority (26.67%) of them were in age range of 31-40 years. About 30% of the patients experienced the first attack of paralysis at the age of 20-24 years. Majority of patients (53%) were from middle class family with occupation of private service (26.66%) and farmer (20%). Positive family history was reported in 20% of patients. Regarding the precipitating factors, majority of patients (83.3%) were related to high carbohydrate meal, 56.67% related to temperature, 41.67% to exercise. Flaccid muscle weakness with variables muscle power (MRC grade 4/5 to 2/5 in 60% and 1/5 to 0/5 in 40%) was found. Cerebellar functions, all modalities of sensations and functions of cranial nerves were intact in all patients. In this series, laboratory investigations revealed reduced serum potassium level (<3mmol/l) in 90% of patients. Serum potassium value >5.5mmol/l was found in only 3.33% of patients. Creatine kinase (MM) was raised in 23% of the patients and Thyroid stimulating hormone (TSH) level was 0.8-2mmol/l in 6% of the patients. More than half of the patients (56%) showed variable ECG changes. Impaired nerve conduction function was found in 28.00%. So, careful history taking, meticulous clinical examination and simple laboratory investigations is sufficient to make a prompt diagnosis and rapid management of patients with periodic paralysis.

Fatal thyrotoxic periodic paralysis with normokalemia.

We present a 10-year-old girl who presented to our emergency services with difficulty in breathing of 2-days duration and progressive weakness of a month's duration. In a previous admission elsewhere, she had not been detected to have hyperthyroidism or electrolyte abnormalities. On admission, the child was in hypercapnic respiratory failure with tachycardia and hepatomegaly. A small goiter as well as signs of thyrotoxicosis were present. Laboratory investigations showed anemia, mildly elevated liver enzymes and serum potassium of 4.8mEq/L. Despite intubation and ventilation and other supportive management including propranolol, the patient could not be saved. Post-mortem biopsy of the thyroid showed diffuse hyperplasia of the follicles and muscles showed evidence of thyroid myopathy.

Normokalemic periodic paralysis revisited: does it exist?

Normokalemic periodic paralysis (normoKPP) is well established in the literature, but there are doubts as to whether it exists as a discrete entity. Retrospective clinical and molecular analysis has confirmed suspicions that most normoKPP families actually have a variant of hyperkalemic periodic paralysis (hyperKPP) due to a mutation of the muscle-specific sodium channel gene (SCN4A). However, the original normoKPP family described by Poskanzer and Kerr (Poskanzer DC, Kerr DNS. A third type of periodic paralysis, with normokalemia and favourable response to sodium chloride. Am J Med 1961;31:328-342) has remained unchallenged. We identified the Met1592Val mutation of SCN4A in an affected descendent of this original normoKPP family. This is the final piece in the puzzle: normoKPP is actually a variant of hyperKPP and is not a distinct disorder.

Total intravenous anaesthesia in a patient with familial hypokalaemic periodic paralysis.

A 35-year-old woman with known familial hypokalaemic periodic paralysis received general anaesthesia for reduction of bilateral breast hyperplasia. Uncomplicated general anaesthesia was performed using a propofol target-controlled infusion, remifentanil infusion and bolus doses of mivacurium with neuromuscular function monitoring. Plasma potassium concentrations were controlled intermittently in the peri-operative period and supplemented to achieve normokalaemia. Despite continuous substitution, an episode of low plasma potassium concentration occurred during the recovery period; this was without any clinical signs of muscle paralysis or respiratory distress.

Dysfunction of sensory nerves during attacks of hypokalemic periodic paralysis.

Reversible electrophysiologic abnormalities of sensory nerve function were found by chance in three patients with hypokalemic periodic paralysis, a disorder previously considered to affect the function of muscle membranes only. A formal, prospective study was therefore conducted. Serial nerve conduction studies were done in ten additional patients. Amplitude of sensory action potentials was significantly smaller during paralytic attacks, but did not differ from controls after normalization of serum potassium concentration. These apparently novel findings might be explained by previous electrodiagnostic studies either not involving the testing of sensory nerves at all, or not being repeated after recovery from an attack. Involvement of sensory nerves in hypokalemic periodic paralysis is suggested to arise through dorsal root ganglia having an incomplete blood-nerve barrier and sensory neurons being particularly vulnerable to derangements affecting nerve cell metabolism. Neuronal inexcitability is postulated to occur consequent upon possible inactivation of the sodium-potassium pump by the low concentration of extracellular potassium. In patients with acute areflexic limb weakness, the diagnosis of hypokalemic periodic paralysis should not be excluded by abnormal results of sensory nerve conduction studies.

Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes.

BACKGROUND: Hypokalemia is a well-known, consistent finding in thyrotoxic periodic paralysis (TPP). It is less well known that hypophosphatemia and mild hypomagnesemia are often present in TPP and that rebound hyperkalemia can occur as a result of potassium therapy. OBJECTIVE: To report the prevalence of these electrolyte abnormalities in 24 episodes of TPP in 19 patients admitted to a single university-affiliated public hospital during a 15-year period. METHODS: The medical records of all patients admitted to the Santa Clara Valley Medical Center in San Jose, Calif, between August 1, 1982, and June 1, 1997, with any type of hypokalemic periodic paralysis were reviewed. In patients with TPP, serum potassium, phosphorus, and magnesium levels were evaluated during and after episodes of paralysis. The administered dose of potassium chloride, recovery time from hypokalemia, and prevalence of rebound hyperkalemia after recovery were also ascertained. Data are presented as mean +/- SD. RESULTS: Hypokalemia was present in all 24 initial episodes of TPP, with serum potassium levels ranging from 1.1 to 3.4 mmol/L (mean, 1.9+/-0.5 mmol/L). After recovery from hypokalemia, the maximum serum potassium level significantly increased, ranging from 4.0 to 6.6 mmol/L (mean, 4.9+/-0.5 mmol/L; P<.001). In 10 (42%) of 24 episodes, rebound hyperkalemia (serum potassium level >5.0 mmol/L) was present. Recovery time did not correlate with the potassium chloride dose administered (r = 0.17). Initial serum phosphorus levels ranged from 0.36 to 0.97 mmol/L (mean, 0.61+/-0.23 mmol/L) (1.1-3.0 mg/dL [mean, 1.9+/-0.7 mg/dL]), with hypophosphatemia present in 12 (80%) of 15 episodes. Serum phosphorus levels significantly increased (P<.01), to 1.26 to 1.74 mmol/L (mean, 1.48+/-0.16 mmol/L) (3.9-5.4 mg/dL [mean, 4.6+/-0.5 mg/dL]), with or without phosphorus replacement therapy. A slight increase in serum magnesium levels after paralysis resolved was observed in all patients (P<.07). No further episodes of paralysis occurred in any patients after they became euthyroid. CONCLUSIONS: Hypokalemia, hypophosphatemia, and mild hypomagnesemia are characteristic features of TPP. Hypokalemia occurred in 100% and hypophosphatemia in 80% of the episodes in our study. Rebound hyperkalemia is a potential hazard of potassium administration and occurred in 42% of 24 episodes.

Effect of high-intensity exercise on arterial blood gas tensions and upper airway and cardiac function in clinically normal quarter horses and horses heterozygous and homozygous for hyperkalemic periodic paralysis.

OBJECTIVE: To determine the effect of exercise on arterial blood gas tensions and upper airway and cardiac function in clinically normal Quarter Horses and horses heterozygous and homozygous for hyperkalemic periodic paralysis (HYPP). ANIMALS AND PROCEDURE: 5 clinically normal Quarter Horses, and 5 heterozygous and 2 homozygous HYPP-affected horses were examined before, during, and after exercise on a high-speed treadmill. Arterial blood gas tensions, ECG, and echocardiogram were obtained prior to exercise. Upper airway endoscopy, collection of arterial blood samples, and continuous electrocardiography were performed during a high-intensity stepwise exercise test. An ECG was obtained within 1-minute after completion of the final step. RESULTS: None of the horses homozygous or heterozygous for HYPP had signs of weakness or muscle fasciculations before, during, or after exercise. Horses homozygous for HYPP had intermittent laryngospasm, dynamic pharyngeal collapse, and appreciable hypoxemia, hypercapnia, and ventricular premature contractions during exercise. Heterozygous and clinically normal horses did not have any abnormalities. Potassium concentration increased significantly above the baseline reference range during exercise in all groups of horses. CONCLUSIONS: Horses homozygous for HYPP had laryngospasm and dynamic pharyngeal collapse associated with exercise, most likely secondary to increase in potassium concentration. Upper airway dysfunction is the most likely cause of hypoxemia and hypercapnia. Cardiac arrhythmias were most likely caused by a combination of hypoxemia and hyperkalemia.

Mutation in DHP receptor alpha 1 subunit (CACLN1A3) gene in a Dutch family with hypokalaemic periodic paralysis.

Hypokalaemic periodic paralysis (HypoPP) is characterised by transient attacks of muscle weakness of varying duration and severity accompanied by a drop in serum potassium concentration during the attacks. The largest known HypoPP family is of Dutch origin and consists of 277 members in the last five generations, 55 of whom have HypoPP inherited in an autosomal dominant pattern. Forty-eight persons including 28 patients with a proven diagnosis of HypoPP were used for linkage analysis. Microsatellite markers were used to exclude 45 to 50% of the genome and linkage to chromosome 1q31-32 was found. No recombinants were found between HypoPP and D1S412 and a microsatellite contained within the DHP receptor alpha 1 subunit (CACLN1A3) gene. A previously reported G to A mutation causing an arginine to histidine substitution at residue 528 in the transmembrane segment IIS4 of the CACLN1A3 gene was shown in patients by restriction analysis of genomic PCR products.

Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features.

Andersen's syndrome is a clinically distinct form of potassium-sensitive periodic paralysis associated with cardiac dysrhythmias. The subtle nature of the cardiac and dysmorphic features may delay the recognition of this syndrome and its potentially lethal cardiac dysrhythmias. The genetic defect in Andersen's syndrome is not genetically linked to other forms of potassium-sensitive periodic paralysis and is probably distinct from the long QT syndrome locus.

Paralisia periódica: estudo anátomo-patológico do músculo esquelético de 14 pacientes / Periodic paralysis: anatomo-pathological study of musculoskeletal of 14 patients

A paralisia periódica é entidade caracterizada por crises de fraqueza muscular relacionadas com alteraçöes do nível sérico de potássio. A biópsia muscular pode mostrar alteraçöes específicas ou inespecíficas. Nosso estudo tem como objetivo a análise de 18 biópsias musculares de 14 pacientes com paralisia periódica (14 hipocalêmica, 2 hipercalêmica). Todas as biópsias mostraram alguma alteraçäo histopatológica. Quatorze biópsias apresentavam vacúolos, que se caracterizavam por serem únicos, de localizaçäo periférica, de aparecimento frequente e preferentemente em fibras do tipo I. Os vacúolos eram mais visualizados naqueles pacientes com longa evoluçäo e sem relaçäo com a frequência de crises. Os agregados tubulares foram encontrados em 10 biópsias principalmente naqueles pacientes com crises frequentes e doença de longa evoluçäo. Em 3 pacientes foram realizadas 2 biópsias, notando-se piora das alteraçöes em 2. Um paciente evoluiu com quadro clínico de miopatia permanente, confirmado pela biópsia muscular. Alteraçöes inespecíficas foram encontradas em graus variáveis em 15 biópsias. Nosso estudo mostra que os vacúolos e os agregados tubulares säo achado frequentes na paralisia periódica, constituindo importante auxílio diagnóstico. Alteraçöes miopáticas evidentes à biópsia sugerem o aparecimento de miopatia permanente, quadro decorrente de doença de longa evoluçäo ou crises severas

Possible normokalemic variant of hyperkalemic periodic paralysis in two horses.

Hyperkalemic periodic paralysis (HPP), characterized by intermittent episodes of muscle fasciculations, profound muscle weakness, and hyperkalemia, has been described in Quarter Horses, Appaloosas, and Paints. In previous reports, the hallmark of this syndrome has been the development of hyperkalemia during each episode. Two affected horses had episodes of paralysis without associated hyperkalemia, demonstrating that normokalemia during an episode otherwise consistent with HPP does not eliminate HPP as a diagnosis. This clinical presentation appeared to be a variant of HPP.

[Primary hypokalemic periodic paralysis. Presentation of 18 cases]. / Parálisis periódica hipokalémica primaria. Presentación de 18 casos.

The clinical features of 16 males and 2 females with hypokalemic periodic paralysis (HPP) are presented. Five patients had familial HPP, 4 thyrotoxic HPP and 9 sporadic disease. The age of onset ranged from 6 to 42 years. Clinical pictures varied from paraparesis to severe quadriplegia. The disease onset was earlier in familial HPP (p < 0.05) while sporadic cases showed the most severe, albeit shorter paralysis (p < 0.05). On admission, serum potassium levels ranged from 1.5 to 3.3 mEq/L; they did not correlate with the severity of paralysis. Glucose-insulin provocation test was positive in 5/5 patients. Oral potassium chloride and amiloride were useful to prevent paralysis. Contrasting with reports from USA and Europe, in México, HPP is not exceptional, and should be considered in the differential diagnosis of acute paralysis.

Linkage of hyperkalaemic periodic paralysis in quarter horses to the horse adult skeletal muscle sodium channel gene.

A genetic disease observed in certain Quarter horses is hyperkalaemic periodic paralysis (HYPP). This disease causes attacks of paralysis which can be induced by ingestion of potassium. Recent studies have shown that HYPP in humans is due to single base changes within the adult skeletal muscle sodium channel gene. A large Quarter horse pedigree segregating dominant HYPP was studied to determine if mutations of the sodium channel gene are similarly responsible for HYPP in horses. We used cross-species, PCR-mediated, cDNA cloning and sequencing of the horse adult skeletal muscle sodium channel alpha-subunit gene to identify a polymorphism, and then used this polymorphism to see if the horse sodium channel gene was genetically linked to HYPP in horses. The sodium channel gene was indeed found to be tightly linked to HYPP (LOD = 2.7, theta = 0). Our results suggest that HYPP in horses involves the same gene as the clinically similar human disease, and indicates that these are homologous disorders. The future identification of the specific sodium channel mutation causing HYPP in Quarter horses will permit the development of accurate molecular diagnostics of this condition, as has been recently shown for humans.

Different gene loci for hyperkalemic and hypokalemic periodic paralysis.

The periodic paralyses are dominantly inherited disorders in which patients acutely develop muscle weakness in association with changes in the level of blood potassium. We recently reported genetic linkage of hyperkalemic periodic paralysis (HIKPP) to the gene encoding the adult form of the skeletal muscle sodium channel on the long arm of chromosome 17. In this paper, we exclude genetic linkage between hypokalemic periodic paralysis (HOKPP) and this sodium channel gene, demonstrating that there is non-allelic genetic heterogeneity among different forms of periodic paralysis. Electrophysiological abnormalities in muscle sodium conductance have been reported for both HIKPP and HOKPP as well as other muscle disorders characterized by membrane hyperexcitability or myotonia (myotonia congenita, paramyotonia congenita and the Schwartz-Jampel syndrome). The possibility that there may be a family of human muscle diseases arising from mutations in the sodium channel suggests these disorders may be classified by categories of mutations within this critical voltage-sensitive membrane protein.

Potential role of acute hypophosphatemia during hypokalemic periodic paralysis attack.

A paralysis attack was induced by glucose load in a patient with hypokalemic periodic paralysis. A profound drop in serum phosphorus was observed (from 3.0 to 0.8 mg/dl) in parallel to the serum potassium decrease. The potential role of phosphorus metabolism in the pathophysiology of muscle weakness in this disease is discussed.