Comparative study of thyrotoxic periodic paralysis from idiopathic hypokalemic periodic paralysis: An experience from India

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).

Materials and 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.

Conclusion:

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.     

Thyrotoxic periodic paralysis and the sodium/potassium pump

The hypothesis of altered Na+/K+ transport in thyrotoxic periodic paralysis (TPP) was tested in an investigation of the K+ influx into erythrocytes from two patients with episodes of thyrotoxic muscle weakness. A patient with primary hypokalemic periodic paralysis (HPP) and three healthy volunteers served as controls. The TPP patients were of Oriental and Caucasian origin and differed in their clinical symptoms. For the Caucasian patient, the Na+ content of the erythrocytes was twice the control, for the Oriental patient it was normal. The K+ dependence of the ouabain-inhibitable K+ influx (the pump action) was also abnormal in the Caucasian patient, the flux being 70% of control at 2 mM [K+]e and normal at 4 mM [K+]e. The K+ influx was normal in the Oriental patient. By contrast, the K+ leak of the cells was normal in the Caucasian and was increased in the Oriental patient. The pump/leak ratio was thus reduced in both TPP patients. All parameters investigated were normal in the patient with primary HPP. It is concluded that the ion transport systems of muscle may be altered in TPP, but that the patho-mechanism might be different in the rare Caucasian cases and the rather more common Oriental cases.     

INa and IKir are reduced in Type 1 hypokalemic and thyrotoxic periodic paralysis

We evaluated voltage‐gated Na⁺ (I_Na) and inward rectifier K⁺ (I_Kir) currents and Na⁺ conductance (G_Na) in patients with Type 1 hypokalemic (HOPP) and thyrotoxic periodic paralysis (TPP). We studied intercostal muscle fibers from five subjects with HOPP and one with TPP. TPP was studied when the patient was thyrotoxic (T‐toxic) and euthyroid. We measured: (1) I_Kir, (2) action potential thresholds, (3) I_Na, (4) G_Na, (5) intracellular [Ca²⁺], and (6) histochemical fiber type. HOPP fibers had lower I_Na, G_Na, and I_Kir and increased action potential thresholds. Paralytic attack frequency correlated with the action potential threshold, G_Na and I_Na, but not with I_Kir. G_Na, I_Na, and [Ca²⁺] varied with fiber type. HOPP fibers had increased [Ca²⁺]. The subject with TPP had values for G_Na, I_Na, action potential threshold, I_Kir, and [Ca²⁺] that were similar to HOPP when T‐toxic and to controls when euthyroid. HOPP T‐toxic TPP fibers had altered G_Na, I_Na, and I_Kir associated with elevation in [Ca²⁺]. Muscle Nerve, 2010     

Muscle membrane excitability after exercise in thyrotoxic periodic paralysis and thyrotoxicosis without periodic paralysis

We evaluated whether the paralytic attacks in thyrotoxic periodic paralysis (TPP) are primarily due to the abnormal excitability of the muscle membrane caused by a preexisting latent abnormality or to the effects of thyroid hormone. The prolonged exercise (PE) test was used to evaluate muscle membrane excitability in 21 patients with TPP and 11 patients with thyrotoxicosis without paralytic attacks (Tw/oPP) in the hyperthyroid state. The PE tests were compared between the hyperthyroid and euthyroid states in five of the TPP and three of the Tw/oPP patients. Compared to 20 healthy subjects, a significant increase in compound muscle action potential (CMAP) amplitudes immediately after exercise and a significant time-dependent gradual decline in CMAP amplitudes starting from 20 min after exercise were observed in the TPP patients. A significant decline in CMAP amplitudes was also observed in the Tw/oPP patients but only at 50 min after exercise. All of the TPP and Tw/oPP patients had a tendency to improve in the euthyroid state; the PE tests remained abnormal only in the TPP patients. Paralytic attacks in TPP patients are due primarily to a preexisting latent abnormal excitability of the muscle membrane, possibly genetic in origin.     

甲亢性及非甲亢性周期性瘫痪的临床和肌电图

目的 探讨甲状腺功能亢进性周期性瘫痪（TPP）与非TPP的临床及肌电图特点。方法 将27例周期性瘫痪（PP）病人分成TPP及非TPP两组,并比较两组病人的诱发因素、近端肌力、血钾以及肌电图。结果 TPP组发病无明确诱发因素较非TPP多（P＜0．05）;肌电图异常者TPP较非TPP多（P＜0．01）;TPP和非TPP累及近端肌群及低血钾发生率相近（P＞0．05）。结论 肌电图在鉴别TPP和非TPP上有重要价值;PP病人应常规作肌电图及甲状腺功能检查,以确定是否有TPP存在。     

Gender differences in penetrance and phenotype in hypokalemic periodic paralysis

Introduction: Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant skeletal muscle ion channelopathy. Sex hormones are natural ion channel regulators. Different sex hormones have different effects on ion channels. A comparison of the penetrance and phenotype between males and females with HypoPP mutations should aid in proving that sex hormones play different roles in HypoPP and also provide the basis for the development of therapies against HypoPP. Methods: We identified all mutation carriers in 4 HypoPP families using PCR sequencing techniques. All patients underwent clinical investigation. Results: There were 8 men and 7 women mutation carriers in the 4 families. Male carriers had 100% penetrance, but female penetrance was only 28.57%. The highest attack frequency was 50–150 times/year for the men, whereas it was 30–50 times/year for the women. The attacks disappeared during pregnancy. Conclusions: The penetrance and attack frequency were lower in women than in men with HypoPP mutations. Muscle Nerve, 2013     

周期性瘫痪患者血清肌酶改变及其临床意义

目的　探讨周期性瘫痪患者发作期肌酶改变及其临床意义。方法　用速率法检测 10 3例周期性瘫痪患者发作期及 35名健康对照者的血清肌酸磷酸激酶 (CPK)、乳酸脱氢酶 (LDH)及天门冬氨酸氨基转移酶 (AST) ,分析肌酶改变与临床的关系。结果　患者各种血清肌酶水平与对照组比较均有显著升高 (均P <0 0 1) ;血清肌酶水平与临床肌力、伴发肌肉酸痛及症状持续时间有关。结论　周期性瘫痪发作期血清肌酶增高的程度及肌肉酸痛的程度可以作为判断病情及估计预后的指标     

Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine

1. 1. This case report of a Chinese male schizophrenic patient describes new side effects that have not been documented previously for patients treated with clozapine. At certain doses of clozapine, the patient showed direct adverse reactions, which include a combination of hyperglycemia, hyperlipemia, and periodic paralysis.

2. 2. In a four-year study of this patient who had no previous episodes of diabetes in his or his family history, the authors found that these symptoms disappeared upon withdrawal of clozapine and relapsed with re-treatment of the drug.

3. 3. This study indicates that hyperglycemia, hyperlipemia, and periodic paralysis may need to be monitored on patients treated with clozapine.

     

In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis

ObjectiveHypokalaemic periodic paralysis (HypoPP) is caused by mutations of Ca_v1.1, and Na_v1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Na_v1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo.MethodsMVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP(n = 7), HypoPP (n = 10), and normal controls (n = 26).ResultsMuscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges.ConclusionsThe in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita.SignificanceMVRCs provide important in vivo data that complements expression studies of ion channel mutations.