Thyrotoxic periodic paralysis in Mexican mestizo patients: a clinical, biochemical and HLA-serological study

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is characterized by episodes of neuromuscular weakness occurring in the context of hypokalemia and hyperthyroidism and has been predominantly described in Oriental populations. Whereas it is uncommon in Caucasians and Blacks, TPP does occur in individuals of Native American descent. The objective was to analyze the clinical, biochemical, and HLA characteristics of a group of Mexican mestizo patients with TPP. METHODS: The sample was comprised of 14 men with TPP diagnosed since January 1990, based on one or more episodes of flaccid paralysis, accompanied by hypokalemia and occurring in the context of clinical and biochemical hyperthyroidism. Eight were available for HLA testing. RESULTS: Hyperthyroidism was diagnosed before the development of periodic paralysis in five of the patients, whereas in six it occurred afterward. The severity of paralysis did not correlate with the degree of either hypokalemia or hyperthyroidism. An increased frequency of HLA-DR3 was found in Graves' patients without paralysis but not in those with paralysis, as compared to the general population. CONCLUSIONS: TPP is more common than previously thought in Mexicans, in whom it behaves as in other Native American groups. The lack of HLA-DR3 association in Graves' patients with TPP is interesting, but at the moment has no pathophysiological implications.     

甲状腺毒性周期性麻痹患者反跳性高钾血症三例报道并文献复习

甲状腺毒性周期性麻痹（TPP）是由甲状腺毒症引起的一种内分泌急症,主要表现为周期性肌无力和低钾血症,严重威胁患者健康。血钾降低的水平与TPP患者肌无力的严重程度密切相关,补钾治疗能快速缓解患者的肌无力症状和低钾血症。但过量补钾治疗会导致TPP患者出现急性反跳性高钾血症,再次威胁患者的健康。本文报道了3例TPP患者因过量补钾治疗而导致急性反跳性高钾血症,分析引起反跳性高钾血症的危险因素,希望为TPP患者的临床治疗提供更多资料。     

甲状腺功能亢进合并低钾血症及周期性麻痹的临床研究

回顾分析1225例甲状腺功能亢进症（甲亢）患者临床资料,了解低钾血症和周期性麻痹的发生情况.其中单纯低钾血症者104例（8.5%）,女性占82.7%（86/104）,血钾为3.10～3.42mmol/L;周期性麻痹者60例（4.9%）,男性占96.7%（58/60）,血钾低于3.0 mmol/L者占93.3%（56/60）.甲亢控制后低钾血症和周期性麻痹均可缓解.     

血睾酮水平与男性甲状腺功能亢进症伴周期性麻痹的关系

目的探讨毒性弥漫性甲状腺肿（Graves病）患者血睾酮水平与周期性麻痹的关系。方法选择男性甲状腺机能亢进症伴周期性麻痹（TPP组）患者组30例,单纯甲状腺机能亢进症（单纯甲亢组）患者组30例,比较两组组间血睾酮水平及相关实验室指标变化。结果TPP组体质量指数（bodymass index,BMI）、血睾酮高于单纯甲亢组（P〈0．05）,游离三碘甲状腺原氨酸（FL）、游离甲状腺素（n）低于单纯甲亢组（P〈0．05）。结论TTP患者存在高睾酮血症,血清钾下降可能与血清睾酮增高、血钾向细胞内转移有关。     

甲亢性周期性麻痹的遗传易感基因研究进展

甲亢性周期性麻痹(TPP)是甲亢的一种合并症,其发生存在着明显的性别和种族差异,由于遗传因素与环境因素相互作用而发病。本文简单介绍了TPP的临床特征和流行病学,报告了与其可能相关的易感基因。     

Hyperthyroidism with Periodic Paralysis

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.

     

甲亢性周期性瘫痪30例临床分析

目的探讨以低钾性瘫痪为主要临床表现的甲状腺功能亢进症(甲亢)的发病相关因素及治疗方法。方法对30例甲亢性周期性瘫痪(TPP)的临床资料进行回顾性分析。结果发作时均有不同程度双下肢或四肢瘫痪;T3、T4均高于正常。结论甲亢性周期性瘫痪以年轻男性多见,补钾短期内可改善TPP症状,抗甲亢治疗是预防TPP复发的关键。     

甲状腺功能亢进合并周期性麻痹18例临床分析

目的 探讨甲状腺功能亢进合并周期性麻痹的临床特点和有效地治疗方法。方法 回顾性分析了18例甲状腺功能亢进合并周期性麻痹患者的临床资料。结果 本组患者发病时均有不同程度的对称性下肢或四肢软瘫，17例伴有血钾降低，18例FT3，FT44均高于正常。结论 补钾治疗后可迅速改善症状，联合抗甲状腺治疗是防止甲状腺功能亢进合并周期性麻痹复发的重要措施。     

20例低血钾型周期性麻痹患者临床和病理分析

目的探讨低血钾型周期性麻痹（hypokalemie period paralysis,HOPP）患者的临床及骨骼肌病理特点。方法回顾性分析2005年9月—-2012年12月在河北医科大学第三医院做骨骼肌活检的HOPP患者20例,均行血钾、肌酸激酶、心电图及甲状腺功能检查。结果20例患者中,原发性HOPP组16例,甲状腺功能亢进合并HOPP组（TPP组）4例。TPP组的起病年龄较原发性HOPP组晚,（42．75±9．36）岁135（24．81±5．49）岁（P〈0．01）;原发性HOPP组与TPP组分别有43．75％（7／16）和25．00％（1／4）的患者存在血清肌酸激酶水平异常增高;2组患者血钾水平差异无统计学意义,（2．82士0．30）mmol／L125（2．58±0．13）mmol／L）;20例患者中,有8例（40．00％）骨骼肌活检见肌纤维胞浆中存在典型“管聚集”现象,其中原发性HOPP组7例,TPP组1例。结论低血钾型周期性麻痹“管聚集”的发病率为40．00％,8例患者存在肌纤维网结构紊乱、“管聚集”现象,原发性HOPP组“管聚集”现象较TPP组更常见;原发性HOPP组发病年龄较早。     

Thyrotoxic periodic paralysis

A young man of 30 yrs got himself admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, Bangladesh with the complaints of suddenly developed weakness in his all four limbs. He had features of hyperthyroidism and he gave the history of similar attacks of weakness in his all four limbs in the previous months. His potassium was in the lower part of the normal range and his T4 and T3 were elevated but TSH was markedly low. He was diagnosed as a case of thyrotoxic periodic paralysis on the basis of clinical and biochemical findings. After treatment with carbimazole, propranolol and potassium replacement, patient's condition improved dramatically.     

SCN4A基因Arg672His突变致低钾性周期性麻痹伴维生素D严重缺乏一例报道并文献复习

低钾性周期性麻痹（HypoPP）是一种常染色体显性遗传性离子通道疾病,以反复发作、骨骼肌松弛性瘫痪、低钾血症为主要特征。研究表明,约60%的HypoPP由CACNA1S基因R528H和RI239H突变导致,中国人群及东亚人群以CACNA1S基因突变多见,而SCN4A基因突变较为少见。本文报道了1例SCN4A基因Arg672His突变所致HypoPP伴维生素D严重缺乏患者,并进行了文献复习,提示维生素D缺乏可能导致腹泻并诱发HypoPP,临床发现低钾血症患者并明确排除其他病因后,需考虑到HypoPP的可能。     

Hyperthyroidism and periodic paralysis

The periodic paralyses are a rare group of disorders which may be familial, sporadic, occur in association with hyperthyroidism or as a result of potassium loss. A 46-year-old otherwise healthy Filipino male is described who presented with a second episode of paroxysmal painless weakness. Examination revealed a pattern of weakness consistent with a myopathic process (symmetric/proximal). The neurologic examination was otherwise physiologic. The clinical features are described as well as the differential diagnosis, pathophysiology, and treatment. This case also demonstrates the phenomenon wherein periodic paralysis may precede clinical hyperthyroidism.     

巴特综合征临床分析

目的 总结巴特综合征的临床特点,探讨其发病机制.方法 回顾性分析天津医科大学总医院内分泌科2006年11月至2010年5月的6例巴特综合征病例.结果 6例患者发病年龄13～35岁,男女比例为5∶1.临床上以乏力(6/6)、发作性四肢软瘫(1/6)、肢体麻木(5/6)、手足搐搦(4/6)等为主要表现;血压正常;实验室检查出现持续性低血钾、代谢性碱中毒(6/6),有血浆肾素活性(6/6)、血管紧张素Ⅱ(6/6)及醛固酮(2/6)升高;三角肌活检病理:肌纤维肿胀变性坏死、肌细胞纤维化和肌横纹消失,多种免疫复合物沿肌膜沉积;肾穿刺病理:肾小球旁器增生(5/6)和肾脏多种免疫复合物沉积.补钾及甲泼尼龙等治疗后症状缓解.结论 巴特综合征的临床特点包括乏力、肢体麻木抽搐、正常血压、低血钾性碱中毒及高肾素活性.检查电解质、血气分析及肾素血管紧张素醛固酮水平可明确诊断.不排除免疫因素参与本疾病过程.

Abstract：

Objective To summarize the clinical characteristics of Bartter syndrome and investigate its pathogenesis. Methods The clinical data of 6 cases of Bartter syndrome at our hospital from November 2006 to May 2010 were analyzed retrospectively. Results The onset age of Bartter syndrome was 13-35years old. The main symptoms included weakness (6/6), paralysis ( 1/6 ), numbness ( 5/6 ) and tetany (4/6). All patients had normal blood pressure. The biochemical tests showed persistent hypokalemia, metabolic alkalosis (6/6) and hyperreninemia. The pathological examination of deltoid muscle biopsy showed the swelling, degeneration and necrosis of myocytes and the deposition of immunocomplex in myolemma. And the pathological examination of renal biopsy showed the hyperplasia of juxtaglomerular apparatus (5/6) and the deposition of immunocomplex.All symptoms were relieved after a therapy of potassium supplementation or a combination of indomethacin, spironolactone and immunosuppressant.Conclusion When such clinical features as weakness, paralysis, tetany, hypokalemic alkalosis and normotension are encountered, Bartter syndrome should be suspected. Serum electrolytes, blood gas analysis and activation of the renin-angiotensin-aldosterone system should be examined for a definite diagnosis. The treatment of choice includes potassium and magnesium supplementation or in combination with prostaglandin synthetase inhibitor, aldosterone antagonist and immunosuppressant. Immunologic mechanism may participate in the course of Bartter syndrome.     

An unusual case of hypokalemic paralysis associated with primary Sjogren's syndrome

43-year-old Caucasian female presented with progressive weakness and dyspnea. She was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:640 and positive antibodies to SSA and SSB. Schirmer's test was normal. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy and corticosteroids. Primary SS should be a differential in premenopausal women with acute weakness and hypokalemia.     

17例Gitelman综合征临床分析

目的分析Gitelman综合征的临床特点和实验室特点,进一步提高诊疗水平。方法对解放军总医院近5年来17例(男/女:11/6)患者进行回顾性研究,对其临床症状、实验室、影像学检查结果及诊治情况进行分析。结果 17例患者中15例均有不同程度的下肢乏力,其中软瘫8例;实验室检查表现为低血钾(17/17),低血镁(17/17)、低尿钙(17/17);血肾素活性(17/17)、血管紧张素Ⅱ(14/17)及醛固酮(7/17)明显升高;单纯补钾或联合消炎痛、安体舒通和门冬氨酸钾镁片等药物治疗后症状缓解,但血钾、血镁未升至正常水平。结论 Gitelman综合征以双下肢乏力为主要临床表现,并伴有低血钾、低血镁等,治疗应以补钾、补镁、醛固酮拮抗剂等多种药物联合应用,预后良好。     

Gitelman综合征合并严重低钠血症的诊治分析

本文报道了1例以间断四肢乏力起病,伴有咳嗽、咳痰、间断发热的患者,经检查发现低血钾、低血镁、低血氯、低尿钙及肾素-血管紧张素-醛固酮系统（RASS）活性增高,同时合并严重低钠血症、肺部感染,临床诊断为Gitelman综合征合并血管升压素分泌不当综合征（SIADH）,经抗感染、限水、补钠及补钾治疗后,患者全身无力症状明显改善,除血镁变化不明显外,其余电解质水平得到显著改善。后期SLC12A3基因检测发现患者为D486N单杂合突变,再次验证了临床诊断。本病例提示当出现严重低钾合并低钠血症,应积极寻找原因鉴别施治。临床工作中发现疾病不能单从一元论解释时,需要从多种病因考虑,避免延误病情。     

Hypokalaemic paralysis

Hypokalaemic paralysis is a relatively uncommon but potentially life-threatening clinical syndrome. If recognised and treated appropriately, patients recover without any clinical sequellae. The syndrome of hypokalaemic paralysis represents a heterogeneous group of disorders characterised clinically by hypokalaemia and acute systemic weakness. Most cases are due to familial or primary hypokalaemic periodic paralysis; sporadic cases are associated with numerous other conditions including barium poisoning, hyperthyroidism, renal disorders, certain endocrinopathies and gastrointestinal potassium losses. The age of onset, race, family history, medications, and underlying disease states can help in identifying the cause of hypokalaemic paralysis. Initial therapy of the patient with hypokalaemic paralysis includes potassium replacement and search for underlying aetiology. Further management depends on the aetiology of hypokalaemia, severity of symptoms, and duration of disease. This review presents the differential diagnosis for hypokalaemic paralysis and discusses management of the syndrome.     

554例内分泌科住院患者低钾血症的病因和临床特点的回顾性分析:来自单中心的研究

目的 探讨低钾血症的病因、临床特点及中重度低钾相关的危险因素。 方法 回顾性分析2006年1月到2018年12月山东省立医院内分泌科住院低钾血症患者554例。根据血钾水平分为轻、中、重度低钾,分析不同低钾程度的临床资料,应用Logistic回归分析评估低钾程度相关的影响因素。 结果 常见的低钾血症的病因依次为糖尿病［109例(19.68%)］、甲状腺功能亢进症［95例(17.15%)］和原发性醛固酮增多症［64例(11.55%)］。随着低钾程度的增加,男性比例、游离三碘甲腺原氨酸(FT3)、二氧化碳结合力(CO₂CP)逐渐升高,年龄、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)逐渐降低。除外病因不明相关的低钾血症,二分类Logistic回归分析结果显示,男性(OR=2.071,P=0.001)是中重度低钾的影响因素,甲状腺功能亢进症(OR=2.953,P<0.001)、原发性醛固酮增多症(OR=2.660,P=0.004)、肾小管酸中毒(OR=4.967,P<0.001)和Gitelman综合征(OR=7.326,P=0.015)患者发生中重度低钾的风险高于糖代谢异常患者。 结论 糖尿病、甲状腺功能亢进症和原发性醛固酮增多症是内分泌科住院患者低钾血症的相关因素,性别、病因是影响低钾严重程度的主要因素。     

表现为严重低钙血症、周期性麻痹的Gitelman 氏综合征

患者,女,63岁,因反复乏力,双下肢瘫痪,双手搐搦50 年,加重2 年入院。查体:P80/min,BP120/70mmHg,BMI23.0kg/m2,WHR0.84,焦虑,四肢肌力正常,膝反射、踝反射轻度减弱。无阳性家族史,无服用利尿剂及泻药史。实验室检查示低血钾(2.77～3.17mmol/L),低血镁(0.31～0.35mmol/L),低血钙(1.79～1.99mmol/L),和低尿钙(0.12～1.10mmol/24h)。血浆肾素活性升高,血浆醛固酮水平正常,PTH水平正常。尿钙及尿肌酐比低(5.17～23.57×10-3mg/mgCr),血气分析显示代谢性碱中毒。在该患者进行的速尿或双氢克尿噻的清除率试验中,使用速尿后其尿量及氯离子的清除率增加,远端肾小管氯离子的重吸收分数降低;而使用双氢克尿噻后以上变化均不明显,提示缺陷位于远曲小管而不是亨利氏襻的厚壁升之段。因此,Gitelman氏综合征(Gitelman'ssyndrome,GS)诊断明确。给予消炎痛50mg,tid治疗3d后,复查患者的血钾水平开始上升,但血镁及血钙水平无明显改善,加用氨苯蝶啶50mg,tid治疗,4d后发现血钾及血钙水平恢复正常,血镁从0.35mmol/L升到0.52mmol/L出院;院外随访18个月,复查血钾、血钙及血镁水平完全恢复正常。GS可伴有严重低钙血症、周期性麻痹,肾脏清除率试验在临床上可帮助诊断,消炎痛及氨苯蝶啶联合应用治疗有效。     

青少年Gitelman综合征2例临床特点及基因分析

目的研究2例Gitelman综合征患者的临床特点及其SLC12A3基因的突变特点,以提高对该病的认识。方法回顾2例临床诊断为Gitelman综合征的青少年男性患者的临床表现、实验室检查结果等,并对SLC12A3基因进行测序,以确定其突变位点。结果2例患者均表现为不同程度的乏力,低血钾、低血镁、低尿钙,及高血浆肾素活性、高醛固酮水平。应用氯化钾缓释片、门冬氨酸钾镁针、钙镁片治疗后,患者乏力有所缓解,但是易反复。基因检测共发现3个SLC12A3基因的突变位点,均为错义突变：Thr163Met、Gly196Val、Arg871His。患者A存在杂合突变（Thr163Met、Arg871His）,患者B存在纯合突变（Gly196Val）。结论SLC12A3基因检测有助于早期明确诊断Gitelman综合征。