OBJECTIVE: Thyrotoxic periodic paralysis (TPP) is characterized by muscle paralysis and significant intracellular potassium movement resulting in hypokalemia. Since TPP is a rare condition, only a few studies have explicated the clinical characteristics of patients with this disease. This study aimed to elucidate the clinical characteristics of patients with TPP by comparing them with those with thyrotoxicosis without paralysis (non-TPP) and sporadic periodic paralysis (SPP).
METHODS: This was a single-center retrospective cohort study. Clinical data of patients with hyperthyroidism (n = 62) or periodic paralysis (n = 92) who were emergently admitted to our hospital was extracted from the electronic medical records and analyzed.
RESULTS: All patients in the TPP group (15 males and 2 females) had Graves\' disease, with 14 being newly diagnosed. The average serum potassium level on admission was 2.3±0.75 mEq/L. No significant correlation was observed among serum potassium level, amount of potassium required for normalization, and thyroid hormone levels. The TPP group showed significantly younger age, higher male ratio and body mass index (BMI), and lower serum potassium and phosphorus levels than the non-TPP group, which comprised 36 patients with Graves\' disease. No significant differences were observed between the TPP and SPP (n = 11) groups in terms of age, sex, BMI, serum electrolyte levels, potassium requirement for normalization, and recovery time.
CONCLUSIONS: Considering that most patients with TPP have undiagnosed Graves\' disease, distinguishing TPP from SPP based on clinical information and course alone is difficult in emergency settings. Therefore, for early detection and launch of specific treatment of Graves\' disease, screening for thyroid hormone and anti-thyroid stimulating hormone receptor antibody levels is necessary when treating patients with periodic paralysis.

The aim of this study was to establish whether bumetanide can abort an acute attack of weakness in patients with HypoPP. This was a randomised, double-blind, cross-over, placebo-controlled phase II clinical trial. Focal attack of weakness was induced by isometric exercise of ADM followed by rest (McManis protocol). Participants had two study visits and received either placebo or 2 mg bumetanide at attack onset (defined as 40 % decrement in the abductor digiti minimi CMAP amplitude from peak). CMAP measurements assessed attack severity and duration. Nine participants completed both visits. CMAP percentage of peak amplitudes in the bumetanide (40.6 %) versus placebo (34.9 %) group at 1hr following treatment did not differ significantly (estimated effect difference 5.9 % (95 % CI: (-5.7 %; 17.5 %), p = 0.27, primary outcome). CMAP amplitudes assessed by the area under the curve for early (0-2hr post-treatment) and late (2-4 h post-treatment) efficacy were not statistically different between bumetanide and placebo (early effect estimate 0.043, p = 0.3; late effect estimate 0.085, p = 0.1). Two participants recovered from the attack following bumetanide intake; none recovered following placebo. Bumetanide was well tolerated but not efficacious to rescue a focal attack in an immobilised hand in the majority of patients, although data supports further studies of this agent.

OBJECTIVE: Primary hypokalemic periodic paralysis (HypoPP) is an inherited channelopathy most commonly caused by mutations in CACNA1S. HypoPP can present with different phenotypes: periodic paralysis (PP), permanent muscle weakness (PW), and mixed weakness (MW) with both periodic and permanent weakness. Little is known about the natural history of HypoPP.
METHODS: In this 3-year follow-up study, we used the MRC scale for manual muscle strength testing and whole-body muscle MRI (Mercuri score) to assess disease progression in individuals with HypoPP-causing mutations in CACNA1S.
RESULTS: We included 25 men (mean age 43 years, range 18-76 years) and 12 women (mean age 42 years, range 18-76 years). Two participants were asymptomatic, 21 had PP, 12 MW, and two PW. The median number of months between baseline and follow-up was 42 (range 26-52). Muscle strength declined in 11 patients during follow-up. Four of the patients with a decline in muscle strength had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis. Fat replacement of muscles increased in 27 patients during follow-up. Eight of the patients with increased fat replacement had no attacks of paralysis during follow-up, and two of these patients had never had attacks of paralysis.
CONCLUSIONS: The study demonstrates that HypoPP can be a progressive myopathy in both patients with and without attacks of paralysis.

Hypokalemic periodic paralysis type 1 (OMIM; HOKPP1) and type 2 (OMIM; HOKPP2) are diseases of the muscle characterized by episodes of painless muscle weakness, and is associated with low potassium blood levels. Hyperthyroidism has been associated with thyrotoxic periodic paralysis (TTPP) (OMIM; TTPP1 and TTPP2), and genetic susceptibility has been implicated. In the present study, the clinical and epidemiological characteristics of patients with TTPP are described, together with their association with genetic variants reported previously in other populations. A prospective and a retrospective search of the medical records of patients who attended the emergency department at the Hospital Universitario \'Dr. Jose E. Gonzalez\' in Monterrey, Nuevo León, Mexico, and were diagnosed with TTPP was performed. A total of 16 gene variants in the genes MUC1, CACNA1S, KCNE3 and SCN4A, and nine ancestry informative markers (AIMs), were analysed by Multiplex TaqMan™ Open Array assay, and a genetic association study was performed. A total of 11 patients were recruited, comprising nine males and two females (age range, 19-52 years) and 64 control subjects. Only two cases (18%) had a previous diagnosis of hyperthyroidism; the rest were diagnosed subsequently with Graves\' disease. Based on the analysis, two DNA variants were found to potentially confer an increased risk for TTPP: S1PR1 rs3737576 [odds ratio (OR), 4.38; 95% confidence interval (CI), 1.08-17.76] and AIM rs2330442 (OR, 4.50; 95% CI, 1.21-16.69), and one variant was suggested to be possibly associated with TTPP, namely MUC1 rs4072037 (OR, 3.08; 95% CI, 0.841-1.38). However, there were no statistically significant associations between any of the 24 DNA variants and TTPP in a population from northeast Mexico.

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BACKGROUND: Hypokalemia is associated with increased morbidity and at times mortality. \"Hypokalemic paralysis\", particularly if recurrent, has often been considered synonymous with \"hypokalemic periodic paralysis (HPP)\"; however, diseases such as Gitelman syndrome (GS), Bartter syndrome (BS), and renal tubular acidosis (RTA) can have identical presentation. We have tried to explore the etiological spectrum along with epidemiological and certain clinical, biochemical, and electrophysiological features in patients with hypokalemic paralysis.
METHODS: In this observational study, 200 appropriate patients with hypokalemic paralysis (serum K+ <3.5 mmol/L) were evaluated for transcellular shift, extra-renal or renal loss of K+ as the underlying etiology of hypokalemia. We took urinary potassium >25 mmol/day as the cutoff for inappropriate renal loss of potassium in presence of hypokalemia. Serum and urinary osmolality along with arterial blood gas analysis were performed in all patients with renal loss of potassium. Serum and urinary sodium, potassium, calcium, magnesium, chloride, and creatinine were measured in normotensive patients with metabolic alkalosis. Hypertensive patients were evaluated with plasma aldosterone and renin activity.
RESULTS: Probable GS topped the list involving 28% individuals of the entire cohort while probable BS, distal RTA, and HPP were diagnosed in 20%, 22%, and 19% cases, respectively. Rural tribal population (61%) and age group of 30-40 years suffered the most (48%) with concentration of cases in hot and humid summer months.
CONCLUSIONS: We suggest that patients with hypokalemic paresis should be evaluated thoroughly to unmask the underlying etiology that may have a different therapeutic and prognostic connotations and not to use the term \"periodic\" in cases of recurrent hypokalemic paralysis.

OBJECTIVE: To obtain minimum point prevalence rates for the skeletal muscle channelopathies and to evaluate the frequency distribution of mutations associated with these disorders.
METHODS: Analysis of demographic, clinical, electrophysiologic, and genetic data of all patients assessed at our national specialist channelopathy service. Only patients living in the United Kingdom with a genetically defined diagnosis of nondystrophic myotonia or periodic paralysis were eligible for the study. Prevalence rates were estimated for England, December 2011.
RESULTS: A total of 665 patients fulfilled the inclusion criteria, of which 593 were living in England, giving a minimum point prevalence of 1.12/100,000 (95% confidence interval [CI] 1.03-1.21). Disease-specific prevalence figures were as follows: myotonia congenita 0.52/100,000 (95% CI 0.46-0.59), paramyotonia congenita 0.17/100,000 (95% CI 0.13-0.20), sodium channel myotonias 0.06/100,000 (95% CI 0.04-0.08), hyperkalemic periodic paralysis 0.17/100,000 (95% CI 0.13-0.20), hypokalemic periodic paralysis 0.13/100,000 (95% CI 0.10-0.17), and Andersen-Tawil syndrome (ATS) 0.08/100,000 (95% CI 0.05-0.10). In the whole sample (665 patients), 15 out of 104 different CLCN1 mutations accounted for 60% of all patients with myotonia congenita, 11 out of 22 SCN4A mutations for 86% of paramyotonia congenita/sodium channel myotonia pedigrees, and 3 out of 17 KCNJ2 mutations for 42% of ATS pedigrees.
CONCLUSIONS: We describe for the first time the overall prevalence of genetically defined skeletal muscle channelopathies in England. Despite the large variety of mutations observed in patients with nondystrophic myotonia and ATS, a limited number accounted for a large proportion of cases.

OBJECTIVE: There is paucity of reports on thyrotoxic periodic paralysis (TPP) from India. We report the patients with TPP and compare them with idiopathic hypokalemic periodic paralysis (IHPP).
METHODS: Patients with hypokalemic periodic paralysis (HPP) treated during the past 11 years were evaluated retrospectively. Their demographic parameters, family history, clinical features, precipitating factors, severity of weakness, laboratory parameters and rapidity of recovery were recorded. The demographic, clinical and laboratory parameters of TPP and IHPP were compared.
RESULTS: During the study period, we managed 52 patients with HPP; nine (17.3%) of whom had TPP and 27 (52%) had IHPP. The demographic, precipitating factors, number of attacks and severity of limb weakness were similar between the TPP and IHPP groups, except in the IHPP group, bulbar weakness was present in four and respiratory paralysis in six, needing artificial ventilation in two patients. Serum potassium was significantly lower in TPP (2.21 ± 0.49) compared with IHPP (2.67 ± 0.59, P = 0.04). Four patients with TPP had subclinical thyrotoxicosis and two had subclinical hyperthyroidism. Rebound hyperkalemia occurred in both TPP and IHPP (three versus eight patients). The recovery was faster in IHPP (26.7 ± 15.4 h) compared with TPP (34.0 ± 14.0 h), but was statistically insignificant.
CONCLUSIONS: TPP constitutes 17.3% of HPP, and absence of clinical features of thyrotoxicosis and subclinical hyperthyroidism in TPP is not uncommon. Clinical features, demographic profile and rebound hyperkalemia are similar in both TPP and IHPP. The serum potassium level is significantly low in the TPP compared with the IHPP group.

This report describes the case of a 29-year-old Chechen refugee with periodic hypokalemic thyreotoxic tetraparesis (PHTP). Besides a partial respiratory insufficiency, the patient was also presented with sinus bradycardia. Medical literature describes several cases of thyreotoxicosis in combination with bradycardia. For the first time, we were able to observe a case of PHTP in combination with sinus bradycardia. PHTP is rarely seen in central Europe. In this case establishing a final diagnosis was difficult because of the concomitant presence of bradycardia and Graves\' disease.

Hypokalemic paralysis is rarely seen as the presenting feature in patients with Gitelman syndrome. We report a Chinese man who presented with periodic paralysis, in whom molecular analysis revealed compound heterozygous inheritance of three mutations of the thiazide-sensitive sodium chloride cotransporter. Family history revealed intrafamilial variation in phenotypes. Gitelman syndrome should be considered as a cause of hypokalemic paralysis, and molecular analysis may help establish the diagnosis.