Diagnosing thyrotoxic periodic paralysis in the ED

Thyrotoxic periodic paralysis (TPP) and sporadic periodic paralysis (SPP) are the most common causes of hypokalemic periodic paralysis (HPP) in EDs in Asia. Their neuromuscular presentations are almost indistinguishable. We conducted this study to identify clinical clues that can help EPs distinguish between TPP and SPP. Thirty-four patients presenting to the ED with HPP were enrolled during a 3-year period. They did not have known hyperthyroidism before the attack and no family history of paralysis. They all had low K(+) excretion rates. Vital signs and blood biochemistry, including acid-base and electrolytes, were measured. TPP was subsequently established by thyroid function tests. Twenty patients had TPP and 14 patients had SPP. There was no significant difference in age and sex distribution between them. Systolic (SBP) but not diastolic blood pressure (SBP 145 +/- 4 vs 128 +/- 4 mm Hg, P < 0.001) and heart rate (106 +/- 3 vs 73 +/- 3 beats/min, P < 0.001) were significantly higher in those experiencing TPP than SPP. Among the biochemical factors, only plasma phosphate concentration (2.2 +/- 0.2 vs 3.2 +/- 0.2 mg/dL, P < 0.001) was significantly lower in those experiencing TPP than SPP. Systolic hypertension, tachycardia, and hypophosphatemia are clinical clues favoring the diagnosis of TPP.     

Drug-induced thyrotoxic periodic paralysis

OBJECTIVE: To report a case of iodine-induced (Jod-Basedow) hyperthyroidism leading to thyrotoxic periodic paralysis (TPP). CASE SUMMARY: 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. DISCUSSION: 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. CONCLUSIONS: 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.     

Severe hypokalemia in thyrotoxic periodic paralysis

Thyrotoxic hypokalemic periodic paralysis is an uncommon but sometimes fatal disease in which early recognition and therapy may prevent untoward complications. The case of a 26-year-old Chinese man who presented to the emergency department with rapidly progressive profound weakness and severe hypokalemia (serum potassium, 1.2 mEq/L) is presented. The patient required endotracheal intubation, ventilatory assistance, and intravenous potassium administration. Emergency medical evaluation and management of this entity are discussed.     

Hypokalemic thyrotoxic periodic paralysis: a case series

Hypokalemic periodic paralysis is a rare and dramatic complication of hyperthyroidism. This series summarizes the clinical and metabolic features of 10 patients who presented to the Western and Sunshine hospitals in Melbourne, Australia, between 1997 and 2002 with thyrotoxic periodic paralysis (TPP). TPP classically presents with proximal lower-limb weakness in the setting of a low potassium level and biochemical evidence of thyrotoxicosis: low thyroid-stimulating hormone levels along with elevated free thyroxine (FT(4)) or free triiodothyronine (FTL(3)). The challenge for emergency physicians is to recognize the association with thyroid disease, since features of hyperthyroidism may not be apparent on history and examination. Acute treatment with potassium supplements and long-term management is aimed at achieving an euthyroid state. Thyrotoxic periodic paralysis is more common in Asian populations; however, increasing immigration from Asia will lead to higher TPP prevalence in Western countries.     

Recent progress on the searchs of pathogenesis of thyrotoxic periodic paralysis

In Japan, more than 60% of hypokalemic periodic paralysis is thyrotoxic instead of familial type frequently experienced in Caucasian countries. The pathogenesis of familial hypokalemic periodic paralysis (FHPP) has been elucidated to be due to the mutation of one of the genes in either Ca(CACN1AS), Na(SCN4A) or K channel(KCNE3). Clinical features of thyrotoxic periodic paralysis (TPP) is very similar to that of FHPP and rigorous attempts have been devoted to the search of the gene mutation of ion channels in TPP. To date, however, no such an attempt has been successful except for the findings of SNiPs in those ion channel genes or in the vicinity of TRE of CACN1AS. Those SNiPs may provide a risk to the attack of TPP. In TPP, we and others reported that the serum insulin level tremendously elevated prior to the attack of paralysis. There were clinical evidences indicating that hypokalemic periodic paralysis is caused by the depolarization block of muscle cell membrane instead of hyperpolarization block once assumed previously. Otsuka reported that insulin can induce depolarization block of muscle membrane in low K concentration by increasing membrane permeability to Na. We have reported that K deficiency and thyroid hormone excess increased NaK-ATPase and may sensitize the muscle membrane to the effect of insulin to cause depolarization in an animal model. In fact, in Japan, incidence of TPP of male decreased from 8.6% in 1958 to 4.3% in 1998. During this 40 years, intake of K was increased from 43 to 65 mEq per day per person as described by the National Survey of Nutrition. The SNiPs of ion channel genes, together with K deficiency or thyroid hormone excess, may provide a risk to the occurrence of TPP.     

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.     

Early diagnosis of thyrotoxic periodic paralysis: spot urine calcium to phosphate ratio

OBJECTIVES: To identify a clinically reliable index of thyrotoxic periodic paralysis (TPP), a life-threatening emergency with unique and effective therapies. DESIGN: Diagnostic study. SETTING: University teaching hospital. PATIENTS: Fifty-three consecutive patients with hypokalemic paralysis during a 3-yr period and 30 thyrotoxic patients without paralysis as the thyrotoxic control group. INTERVENTIONS: For patients with hypokalemic paralysis, blood and second-void spot urine samples were obtained and measured by routine laboratory prior to therapy. For the thyrotoxic control group, blood and spot urine were collected when they visited outpatient clinics. MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients fulfilled the criteria for TPP. Compared with the thyrotoxic control group, the TPP group had significant decreases in plasma potassium (K) and phosphate concentrations associated with very low urine K and phosphate excretion. Compared with the non-TPP group, the TPP group had significantly lower plasma creatinine and phosphate levels, a significantly higher urine calcium to creatinine ratio (0.25 +/- 0.12 vs. 0.08 +/- 0.07 mg/mg, p < .001), and a significantly lower urine phosphate to creatinine ratio (0.08 +/- 0.05 vs. 0.31 +/- 0.23 mg/mg, p < .001). The urine calcium to phosphate ratio had greater discriminatory power between TPP and non-TPP hypokalemic paralysis (4.1 +/- 2.3 vs. 0.5 +/- 0.6 mg/mg, p < .001). Using a urine calcium to phosphate ratio cutoff value of 1.7 mg/mg, sensitivity and specificity for TPP were 100% and 96%, respectively. CONCLUSIONS: Hypercalciuria and hypophosphaturia are characteristic features of TPP.     

Hypokalaemic thyrotoxic periodic paralysis in an Asian man in the United Kingdom

A large number of ethnic Chinese and other oriental populations are living in the West because of the modern day migration of people. Hypokalaemic periodic paralysis attributable to thyrotoxicosis is a common presentation in an Asian emergency department. It is uncommon in the white communities. There is a difference in the genetic type in the different racial groups. Thyrotoxic features are often masked or absent. Life may be threatened because of severe hypokalaemia and therefore a prompt diagnosis of this condition in the certain ethnic group presenting with weakness and hypokalaemia is essential. Thyroid function studies are mandatory in these cases.     

An unrecognized cause of recurrent hypercalcemia: immobilization

We report a 66-year-old Chinese man with chronic renal insufficiency (creatinine 1.7 mg/dL) and gout suffering from slurred speech and right hemiplegia for 3 days. Acute cerebral infarction was confirmed by computed tomography. Conscious disturbance occurred on the tenth hospital day without significant changes on imaging study when compared with a previous scan. Hypercalcemia (total calcium 14.1 mg/dL) and acute exacerbation of chronic renal failure (serum creatinine 2.5 mg/dL) were noticed. Hypercalciuria (FECa 3.2%), and low serum levels of intact parathyroid hormone and 1,25(OH)2D3 suggested nonparathyroidal hypercalcemia. An extensive workup failed to identify any etiology of hypercalcemia. Hypercalcemia and renal failure were temporarily ameliorated after aggressive volume expansion and loop diuretic treatment but recurred 2 weeks later. Immobilization hypercalcemia was considered after the exclusion of other discernible causes and was successfully treated with rehabilitative exercises and bisphosphonates without further recurrence during a 2-year follow-up. Clinical alertness to immobilization as a possible cause of hypercalcemia may avoid unnecessary and invasive examinations, life-threatening complications and annoying recurrences.     

甲状腺毒症周期性瘫痪与rs312691多态性关联的meta分析

目的 探讨KCNJ2基因下游rs312691多态性是否与甲状腺毒症周期性瘫痪（thyrotoxic periodic paralysis, TPP）发病有关。方法 计算机检索PubMed、Embase、万方和中国知网数据库,收集关于rs312691单苷酸多态性（single nucleotide polymorphism, SNP）与TPP的病例对照研究文献。利用meta分析的方法评价该位点多态性与TPP之间的关系。结果 共纳入7篇文献,共计961例患者,其中TPP组610例,对照组351例。Meta分析结果显示rs312691多态性与TPP的发生有关（OR=3.072,95%CI 2.590 3.643,P＜0.01）,剔除对照组不符合哈-温平衡后的亚组分析依然显示rs312691能增加TPP的风险（OR=2.804,95%CI 2.304 3.413,P＜0.001）。结论 rs312691单核苷酸多态性能增加发生TPP的风险。     

Potassium chloride supplementation alone may not improve hypokalemia in thyrotoxic hypokalemic periodic paralysis

This article reports a 29-year-old man who came to the Emergency Department because of sudden onset of bilateral lower extremity weakness and inability to walk after intake of a high carbohydrate meal and alcohol. He was found to have severe hypokalemia, with K(+) level at 1.7 mmol/L. However, after administration of potassium chloride (KCl), 10 mEq/h intravenous (i.v.) drip for 4 h, follow-up serum potassium was even lower at 1.5 mmol/L and the patient complained of persistent weakness. Twenty mg of propranolol, a non-selective beta-blocker, was given orally and a dramatic improvement of muscle power to grade 5 was noted after 30 min of administration. On the fifth day after discharge, he had another episode of bilateral lower extremity weakness after ingesting a mouthful of alcohol. Muscle power recovered completely after i.v. drip of KCl, 20 mEq. Laboratory data revealed an underlying primary hyperthyroidism for which he was given anti-thyroid agents and beta-blockers.     

The pitfalls of potassium replacement in thyrotoxic periodic paralysis: a case report and review of the literature

Thyrotoxic Periodic Paralysis is an uncommon disorder seen primarily in Asian males and caused by excessive thyroid hormones. This is an endocrine emergency that can lead to respiratory failure, dysrhythmia, and death. The mainstay of therapy has been potassium replacement, however, recent evidence suggests propranolol is a more effective therapy. We present a severe case of TPP in a 22-year-old Latino male with rapidly progressive ascending paralysis and hypokalemia severe enough to lead to cardiac arrest.     

Hypertension in the ED: still an unrecognized problem

Introduction

Hypertension is prevalent in the general population. Emergency Department (ED) follow-up studies show persistence of blood pressure elevations in up to 50% of patients, and ED screening for hypertension has been recommended. Blood pressure elevations are often ignored or attributed to pain or anxiety. Our purpose was to document the incidence and recognition of hypertension in the ED and to assess its relation to pain scores and age.

Methods

This was a retrospective study. Patients presenting to the ED during a 1-month period were included. Age, blood pressure, and pain scores were reviewed. Discharge instructions and diagnoses were assessed as to whether blood pressure was recognized or follow-up was recommended.

Results

There were 2821 patients. Fifteen percent were less than 18 years old. Twenty-six percent had an elevated blood pressure (40% of pediatric patients). There was no correlation between the distribution of pain scores in either children or adults. There was almost no recognition of the problem. Follow-up for elevated blood pressure was recommended in only 4%. Of these, only 46% actually received follow-up. Twenty-four percent of patients with elevated blood pressure received follow-up for other reasons. Blood pressure was still elevated in 47%.

Conclusion

Hypertension was a common problem in our patient population. Elevated blood pressure readings were almost uniformly ignored or unrecognized, particularly in children. There was no correlation of elevated blood pressure readings and acute pain scores. Elevated blood pressure readings should not be attributed solely to anxiety or acute pain on presentation.     

CACNA1S基因多态性引起甲状腺毒性低钾周期性麻痹的研究进展

目的 低钾周期性麻痹作为一种常见的并发症,好发于甲状腺毒症的亚洲男子.造成低血钾症和肌麻痹的原因是钾离子突然的细胞内移,而非机体内钾的不足.伴有低钾周期性麻痹的甲状腺毒症患者的临床特点可能是不典型的,不易被临床医生识别.甲状腺毒性低钾周期性麻痹(1PP)的遗传易感性并不完全清楚,编码L型钙通道亚基(cavl.1)的基因CACNA1S多态性与TPP相关已被注意到.本文旨在探讨TPP的临床表现,以及其发病与钙离子通道及CACNA1S基因多态性关系的研究进展.     

Cation transport across lymphocyte plasma membranes in euthyroid and thyrotoxic men with and without hypokalaemic periodic paralysis

1. To study potassium transport in hypokalaemic periodic paralysis in a model of striated muscle cells, we measured specific [3H]ouabain binding (the number of sodium-potassium pumps), sodium-potassium-pump-mediated (ouabain-sensitive) 86Rb+ influx and sodium-potassium-pump-independent (ouabain-resistant) 86Rb+ influx in lymphocytes in vitro. 2. The subjects comprised euthyroid and thyrotoxic men with hypokalaemic periodic paralysis between attacks, men with uncomplicated thyrotoxicosis, and healthy men matched for age and weight. 3. Thyrotoxic patients, both with and without periodic paralysis, had significantly more lymphocyte sodium-potassium pumps than normal, and a significantly greater sodium-potassium-pump-mediated 86Rb+ influx. Anti-thyroid treatment corrected this defect in patients with thyrotoxic periodic paralysis. Euthyroid patients with cryptogenic periodic paralysis had significantly increased sodium-potassium-pump-mediated 86Rb+ influx, but a normal number of sodium-potassium pumps. 4. Only untreated thyrotoxic and euthyroid patients with periodic paralysis showed a significant increase in sodium-potassium-pump-independent 86Rb+ influx (5.2 +/- 2.8 and 4.5 +/- 1.8 respectively, vs control 2.8 +/- 1.0 pmol h-1 10(-6) cells; mean +/- SD; P less than 0.001, P less than 0.005). 5. We conclude that thyrotoxicosis increases the number and activity of sodium-potassium pumps and facilitates, but is probably not necessary for, periodic paralysis. Hypokalaemic periodic paralysis is associated with an increase in sodium-potassium-pump-independent potassium influx.     

An often unrecognized cause of thunderclap headache: reversible cerebral vasoconstriction syndrome

Thunderclap headache (TCH) can have several causes of which subarachnoid hemorrhage (SAH) is most common and well known. A rare cause of TCH is the reversible cerebral vasoconstriction syndrome (RCVS) which is characterized by a reversible segmental vasoconstriction of the intracranial vessels. We describe two patients with TCH due to RCVS and the probable precipitating factor, namely, cannabis and an anti-migraine drug. In RCVS, cerebrospinal fluid examination is (near) normal, in contrast to SAH and (primary) cerebral vasculitis. Brain MRI may be normal or shows infarction. MRA can demonstrate vasoconstriction of the great arteries, but a normal MRA does not rule out the diagnosis. Caliber changes on cerebral angiography cannot adequately differentiate between RCVS and vasculitis. Calcium-channel antagonists may be a good therapy and repeated transcranial Doppler ultrasonography can be a reliable non-invasive investigation to monitor the effect of treatment and demonstrate reversibility of the vasoconstriction.