Attack Of Thyrotoxic Periodic Paralysis Research Articles

SAT449 Clinical Characteristics Of Patients With Thyrotoxic Periodic Paralysis; An Experience From A Tertiary Care Hospital

Abstract Disclosure: T. Park: None. I. Goak: None. H. Jin: None. K. Lee: None. Y. Kim: None. Backgrounds: Thyrotoxic periodic paralysis (TPP) is a life-threatening complication characterized recurrent episodes of hypokalemia and muscle weakness in the setting of thyrotoxicosis. The present study aimed to describe clinical manifestation and outcome of patients admitted for TPP in emergency department (ED). Methods: This retrospective study analyzed 42 patients with TPP who were admitted ED from January 2000 through December 2020 in a single tertiary referral hospital. Their clinical characteristics were reviewed retrospectively. Results: 42 patients with TPP were identified. The mean age of the patients was 35.0±12.4 years; all were males. The month in which the most patients occurred paralysis symptoms was February (16.7%), followed by October (14.3%). 5 patients had a history of severe exertion, 7 patients had ingested a heavy carbohydrate meal, one patient had an infection, 5 patients had ingested alcohol, but more than half of the patients (57.1%) were without a precipitating cause. TPP was the first presentation of thyrotoxicosis in 85.7% of patients. The most common cause of thyrotoxicosis in TPP patients was Graves' disease (88.1%). At the time of admission, the mean potassium level was 2.77±0.93 mmol/L (reference, 3.5-5.5), mean ionized calcium level was 1.17±0.15 mmol/L (1.13-1.32), mean Free T4 level was 43.36±16.92 pmol/L (11.5-22.7). About half of the patients (47.6%) suffered at least one further attack of TPP. 28 patients (66.7%) diagnosed with Graves’ disease had anti-thyroid drugs alone and 5 patients (11.9%) with thyrotoxic relapses eventually underwent radioactive iodine therapy. None of the patients underwent surgery. Conclusions: TPP can be the presenting feature of previously undiagnosed thyrotoxicosis and should be considered in the differential diagnosis in patients presenting with acute onset of motor paralysis. At the time of the TPP attack, a detailed interview and inquiry with a thorough physical examination usually provide clues to the diagnosis. Presentation: Saturday, June 17, 2023

A Case of Recurrent Paralysis and Low Potassium: Is It the Thyroid?

Introduction: Thyrotoxic periodic paralysis (TPP) is a rare complication of hyperthyroidism that is characterized by episodes of hypokalemia and acute weakness. Although hyperthyroidism is more common in females, over 95% of cases of TPP have been observed in males, especially in Asian males with an incidence of 2% among hyperthyroid patients. In non-Asian populations, the incidence in hyperthyroid patients is estimated to be around 0.1 to 0.2% [1]. We describe a case of TPP seen in a Hispanic male. Case Report: A 36-year-old Hispanic male with no past medical history presents with weakness in all extremities and difficulty breathing after consuming a carbohydrate heavy meal the night prior. He reports a recent, similar episode evaluated in another ER, which resolved after given potassium supplementation. He denied any vomiting, diarrhea, polyuria, diaphoresis, use of insulin or other medications, or any family history of paralysis.His labs were significant for hypokalemia of 1.9, TSH of <0.005 (0.358-3.740), free T4 of 2.22 (0.76-1.46), and total T3 of 2.7 (0.60-1.81). Thyroid stimulating immunoglobulin was 0.12 (0.0-0.55). His symptoms improved and potassium levels normalized following the administration of potassium chloride. He was discharged on propranolol and advised to follow up for further workup of his hyperthyroidism with radioactive iodine uptake scan. Discussion: Thyrotoxic periodic paralysis is a potentially life-threatening condition associated with cardiac arrhythmias and respiratory failure. Hyperthyroidism increases response to β-adrenergic stimulation, which increases activity of the sodium-potassium ATPase and causes hyperpolarization of skeletal muscle [2]. Hyperthyroid patients are prone to episodes of paralysis due to their increased susceptibility to the hypokalemic action of insulin, which activates the sodium-potassium ATPase pump, and epinephrine, which stimulates β-adrenoreceptors. Management of an acute attack of TPP includes potassium administration. In cases where paralysis and hypokalemia are not reversed, intravenous propranolol has been shown to resolve the attack by blocking the β-adrenergic receptors. Definitive treatment of TPP includes managing the hyperthyroid state with medical therapy, radioactive iodine therapy, or surgery. Until the euthyroid state is reached, a β-blocker can prevent episodes of acute paralysis. Avoidance of carbohydrate heavy meals, exercise, and stress are recommended as these factors can potentially exacerbate hypokalemia. In patient with acute paralysis, it is important to consider the diagnosis of TPP as this condition can be prevented once euthyroidism is achieved. Diagnosis and management will lead to prevention of morbidity and mortality associated with the hypokalemia.

Thyrotoxic Periodic Paralysis: Clinical Challenges

Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis. The underlying hyperthyroidism is often subtle causing difficulty in early diagnosis. Factors like high-carbohydrate meal exercise, steroid, and stress can precipitate an attack of TPP. Evidence is building up showing role of genetic mutations in Kir2.6 channel in the pathogenesis of TPP. Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia. Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes are characteristic of TPP. Treatment with low-dose potassium supplements and nonselective beta-blockers should be initiated upon diagnosis, and the serum potassium level should be frequently monitored to prevent rebound hyperkalemia.

THYROTOXIC PERIODIC PARALYSIS: DIAGNOSIS, MANAGEMENT AND ROLE OF PROPRANOLOL IN TREATMENT

Background: Hypokalemia is commonly encountered during paralysis in patients with thyrotoxic periodic paralysis (TPP) and may contribute to neuromuscular manifestations. This condition mainly affects male patients of Asian descent. With increasing population mobility and admixture, TPP as the presenting feature of hyperthyroidism is more common in Western countries and Gulf area. TPP is an alarming and potentially lethal complication of hyperthyroidism characterized by muscle paralysis and hypokalemia due to a massive intracellular shift of potassium. A potassium supplement has been recommended to hasten recovery and prevent cardiopulmonary complications. However, this recommendation has not yet proven efficacious. Hyperadrenergic activity has been implicated in the pathogenesis of TPP. We tested whether nonselective β-blockers could terminate neuromuscular symptoms rapidly while reducing an intracellular shift of potassium. Methods: We describe 7 patients who had an acute attack of TPP with characteristic hypokalemia. Results: After oral propranolol, 3 mg/kg, serum potassium concentrations increased promptly in all patients, and there was complete amelioration of paralysis. Only 3 patient needed short term K supplement for their sever hypokalemia and sever symptoms. No rebound hyperkalemia was detected. Conclusion: Given propranolol efficacy in this study, propranolol should be considered as a first-line therapy for TPP. Key words: Hypokalemia, TPP, hyperthyroidism, propranolol, periodic paralysis

Analytic Review: Thyrotoxic Periodic Paralysis: A Review

Thyrotoxic periodic paralysis (TPP) is an unusual complication of hyperthyroidism that frequently presents in a dramatic fashion, necessitating treatment in an emergency department or admission to an intensive care unit. Thyrotoxic periodic paralysis is characterized by transient, recurrent episodes of flaccid muscle paralysis affecting proximal more severely than distal muscles. Thyrotoxic periodic paralysis is most commonly a complication of Graves' disease in Asian males, although in recent decades, an increasing number of patients from all racial and ethnic backgrounds have been reported. Thyrotoxic periodic paralysis has a higher predilection for men than women despite the fact that thyroid disease is more frequently diagnosed in women. The presence of both hypokalemia and elevated levels of triiodothyronine (T3) and thyroxine (T4) are important diagnostic features during the acute episode. Treatment of TPP involves 2 steps, immediate action to reverse the paralysis followed by measures to prevent future attacks by restoration of a euthyroid state. Although the mainstay of treating an acute attack of TPP is correction of hypokalemia to avoid fatal cardiac arrhythmias and reverse muscle weakness, it must be appreciated by treating physicians that patients with TPP do not have a total body deficiency of potassium. Close attention must be given to potassium replacement as overly aggressive treatment can result in hyperkalemia. Correction of hypokalemia and the underlying thyrotoxic state usually results in amelioration of the acute attack. This review summarizes the epidemiology, clinical manifestations, pathogenesis, diagnosis, and treatment 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.

Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis

Hypokalemia and hypophosphatemia are commonly encountered during paralysis in patients with thyrotoxic periodic paralysis (TPP) and may contribute to neuromuscular manifestations. Potassium and phosphate supplements have been recommended to hasten recovery and prevent cardiopulmonary complications. However, this recommendation has not yet proven efficacious. Hyperadrenergic activity has been implicated in the pathogenesis of TPP. We tested whether nonselective β-blockers could terminate neuromuscular symptoms rapidly while reducing an intracellular shift of potassium and phosphate. We describe two patients who had an acute attack of TPP with characteristic hypokalemia and hypophosphatemia associated with low urinary potassium and phosphate excretion. After oral propranolol, 3 mg/kg, serum potassium and phosphate concentrations increased promptly in 2 hours in both patients, and there was complete amelioration of paralysis. No rebound hyperkalemia or hyperphosphatemia was detected. Given their efficacy in this pilot study, they should be considered as a first-line therapy for TPP.

Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis

Hypokalemia and hypophosphatemia are commonly encountered during paralysis in patients with thyrotoxic periodic paralysis (TPP) and may contribute to neuromuscular manifestations. Potassium and phosphate supplements have been recommended to hasten recovery and prevent cardiopulmonary complications. However, this recommendation has not yet proven efficacious. Hyperadrenergic activity has been implicated in the pathogenesis of TPP. We tested whether nonselective β-blockers could terminate neuromuscular symptoms rapidly while reducing an intracellular shift of potassium and phosphate. We describe two patients who had an acute attack of TPP with characteristic hypokalemia and hypophosphatemia associated with low urinary potassium and phosphate excretion. After oral propranolol, 3 mg/kg, serum potassium and phosphate concentrations increased promptly in 2 hours in both patients, and there was complete amelioration of paralysis. No rebound hyperkalemia or hyperphosphatemia was detected. Given their efficacy in this pilot study, they should be considered as a first-line therapy for TPP.

Thyrotoxic periodic paralysis and intravenous propranolol in the emergency setting

A 27-year-old male of Malaysian descent presented to the Emergency Department (ED) with rapidly progressive flaccid paralysis that quickly compromised his respiratory effort. The patient was found to have a serum potassium of 1.9 meq/L, and was diagnosed as having an acute paralytic episode secondary to thyrotoxic periodic paralysis. The paralytic attack was aborted with a combination of potassium replacement and parenteral propranolol in large doses. We report the use of a rarely described, yet possibly more effective, therapy for an acute attack of thyrotoxic periodic paralysis.

Transient Glucose Intolerance during Attacks of Thyrotoxic Periodic Paralysis

In a 19-year-old Japanese male (case 1) with thyrotoxic periodic paralysis (TPP), an increase of plasma glucose concentration together with abnormally high levels of serum immunoreactive insulin (IRI) was observed preceding a spontaneous attack of paralysis. Therefore, the plasma glucose, glucagon, epinephrine, norepinephrine, serum IRI, growth hormone and cortisol levels, and the erythrocyte insulin receptors were measured in case 1 and a 40-year-old Japanese male (case 2) with TPP during attacks of paralysis induced by prolonged glucose loading. In case 1, the serum IRI concentration was elevated to the extraordinarily high level of 655.0 microU/ml at the beginning of paralysis, and at that time, the plasma glucose concentration was 147 mg/dl. However, when paralysis was not induced by a similar glucose loading during methimazole treatment, the serum IRI and plasma glucose levels at the corresponding time after glucose loading were 20.9 microU/ml and 87 mg/dl, respectively. Furthermore, the affinity of the erythrocyte insulin receptors was decreased during the attack. In case 2, plasma glucose and serum IRI concentrations were increased in accordance with the initiation of paralysis although the blood levels of hormones counteracting insulin were not significantly changed. These findings suggest that there is something interacting with the normal action of the insulin in the early phase of paralysis.

STUDIES ON THE INTRACELLULAR WATER, SODIUM AND POTASSIUM IN THYROTOXIC MYOPATHY AND IN THYROTOXIC PERIODIC PARALYSIS

Biochemical analysis of intracellular water, sodium, potassium and nitrogen in biopsied muscle was attempted in 24 thyrotoxic myopathy, in 10 thyrotoxic periodic paralysis and in 19 control subjects. Water and electrolytes studies were done by chloride assumption.1. Serum electrolytes in all groups remained in normal range except remarkable fall of potassium during paralytic attack of thyrotoxic periodic paralysis.2. In thyrotoxic myophathy, total and intracellular water in solid tissue basis decreased by 11.6% and 12.9% respectively, through no significant alteration was observed in thyrotoxic periodic paralysis during either paralytic or non-paralytic state.3. Intracellular sodium content and concentration in muscle specimen increased in thyrotoxicosis and in thyrotoxic periodic paralysis during non-paralytic state. Intracellular potassium, in reverse, decreased significantly in either thyro toxicosis or during paralytic attack of thyrotoxic periodic paralysis. However in non-paralytic state intracellular potassium concentration did not differ significantly from control subjects.4. Since decrease of total nitrogen in biopsied specimen (10.4%) limited by half of the decrease of intracellular potassium (20.8%), this potassium depletion was not the result by muscle destruction.5. Linear correlation between grip strength and intracellular potassium concentration of biopsied muscle was proved in thyrotoxic myopathy.