Thyrotoxic Periodic Paralysis: Clinical Challenges

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Hyperthyroidism is more common in females, with a female-to-male ratio of 9:1.

“The male to female ratio ranges from 17 : 1 to 70 : 1 despite the fact that hyperthyroidism is more common in females (female-to-male ratio of 9 : 1) [6].”

• cites [6] 1996, QJM sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Neurologic examination during an attack of TPP demonstrates weakness, usually affecting proximal more than distal muscles, and the legs more than the arms.

“Neurologic examination during an attack demonstrates weakness, usually affecting proximal more than distal muscles, and the legs more than the arms.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Thyrotoxic periodic paralysis (TPP) is a disorder most commonly seen in Asian men.

“Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis.”

• cites [2] sourceNot checked yet

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May combine two claims.

In TPP, reduced outward K+ current because of loss-of-function mutations of Kir2.6 causes a similar imbalance between inward leak current and outward K+ current, and it results in paradoxical depolarization.

“In TPP, reduced outward K+ current because of loss-of-function mutations of Kir2.6 causes a similar imbalance between inward leak current and outward K+ current, and it results in paradoxical depolarization.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

TPP primarily affects the lower extremities and is secondary to thyrotoxicosis.

“The condition primarily affects the lower extremities and is secondary to thyrotoxicosis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The incidence of TPP in Japanese thyrotoxic patients is 1.9%.

“The incidence of TPP in Chinese and Japanese thyrotoxic patients has been reported at 1.8% and 1.9%, respectively [2], whereas in North Americans at 0.1%–0.2% [5].”

• cites [2] sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Exercise releases potassium from the skeletal muscles, whereas rest promotes influx of potassium.

“Exercise releases potassium from the skeletal muscles, whereas rest promotes influx of potassium.”

Probably not a substantial claim: may not pass S3 (load-bearing).

TPP is characterized by acute onset of severe hypokalemia and profound proximal muscle weakness in patients with thyrotoxicosis.

“TPP is characterized by acute onset of severe hypokalemia and profound proximal muscle weakness in patients with thyrotoxicosis [4].”

• cites [4] 1967, The British Medical JournalNot checked yet

  Not checked in the free run.

May combine two claims.

Kir2.6 forms functional homotetramer and heterotetramer with Kir2.1.

“Cheng et al. also reported that Kir2.6 forms functional homotetramer and heterotetramer with Kir2.1, another Kir channel in the skeletal muscle.”

• cites [19] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Among hypokalemic periodic paralysis, familial hypokalemic periodic paralysis (FPP) is the most common cause in Western countries, and TPP is the most common cause in Asia.

“Among the hypokalemic periodic paralysis, familial hypokalemic periodic paralysis (FPP) is the most common cause in Western countries, and thyrotoxic periodic paralysis (TPP), characterized by the triad of acute hypokalemia without total body potassium deficit, muscle paralysis, and thyrotoxicosis, is the most common cause in Asia.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The incidence of TPP in Chinese thyrotoxic patients is 1.8%.

“The incidence of TPP in Chinese and Japanese thyrotoxic patients has been reported at 1.8% and 1.9%, respectively [2], whereas in North Americans at 0.1%–0.2% [5].”

• cites [2] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The incidence of TPP in North Americans is 0.1%-0.2%.

“The incidence of TPP in Chinese and Japanese thyrotoxic patients has been reported at 1.8% and 1.9%, respectively [2], whereas in North Americans at 0.1%–0.2% [5].”

• cites [5] 1989, Archives of Internal Medicine sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Patients with TPP are usually young adult males 20-40 years of age.

“Patients are usually young adult males 20–40 yr of age.”

May combine two claims.

Testosterone enhances hypertrophy of myoblasts and thus causes higher muscle-to-body mass ratio and total Na+/K+-ATPase abundance in males.

“Testosterone enhances hypertrophy of myoblasts and thus causes higher muscle-to-body mass ratio and total Na+/K+-ATPase abundance in males.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The male to female ratio of TPP ranges from 17:1 to 70:1.

“The male to female ratio ranges from 17 : 1 to 70 : 1 despite the fact that hyperthyroidism is more common in females (female-to-male ratio of 9 : 1) [6].”

• cites [6] 1996, QJM sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Mild myalgia is a complaint in less than half of patients with TPP.

“Mild myalgia is a complaint in less than half of patients [21].”

• cites [21] sourceNot checked yet

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May combine two claims.

Insulin and catecholamine not only activate Na+/K+ ATPase but also inhibit Kir channels.

“Moreover, insulin and catecholamine not only activate Na+/K+ ATPase but also inhibit Kir channels [17].”

• cites [17] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Chinese thyrotoxic patients, TPP occurs in 13% of males and 0.17% of females.

“In the Chinese, TPP occurs in 13% of male and 0.17% of female thyrotoxic patients, in a series published in 1967 [4].”

• cites [4] 1967, The British Medical JournalNot checked yet

  Not checked in the free run.

May combine two claims.

Hyperinsulinemia is observed in acute attack of TPP, and the release of insulin in response to oral glucose challenge is exaggerated in TPP patients.

“Hyperinsulinemia is also observed in acute attack of TPP, and the release of insulin in response to oral glucose challenge is exaggerated in TPP patients, supporting the idea that insulin participates in the pathogenesis of hypokalemia in TPP [9].”

• cites [9] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

TPP is more commonly reported in oriental Asians.

“Thyrotoxic periodic paralysis (TPP) is more commonly reported in oriental Asians [2].”

• cites [2] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

TPP has also been reported from western countries as a result of migration of different ethnic populations.

“It has also been reported from the western countries as a result of migration of different ethnic populations [3].”

• cites [3] 1992, Medicine sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia, leading to paradoxical depolarization with consequent inactivation of Na+ channel and muscle inexcitability.

“Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia, leading to paradoxical depolarization with consequent inactivation of Na+ channel and muscle inexcitability [20].”

• cites [20] sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

TPP is commonly misdiagnosed in Western countries because of its similarities to familial periodic paralysis.

“TPP is commonly misdiagnosed in Western countries because of its similarities to familial periodic paralysis.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Increased outdoor activity with increased perspiration of potassium and ingestion of sugar-containing cold beverages may be responsible for the higher prevalence of TPP attacks in the summer and fall.

“With respect to the seasonal variation, increased outdoor activity with increased perspiration of potassium and ingestion of sugar-containing cold beverages may be responsible for the higher prevalence of TPP attacks in the summer and fall.”

May combine two claims.

Mutations in the gene encoding Kir2.6 are associated with TPP and predispose these patients to acute paralytic attacks.

“Recent studies have shown that mutations in the gene encoding Kir2.6, a skeletal muscle-specific Kir channel, are associated with TPP and predispose these patients to acute paralytic attacks.”

• cites [18] sourceNot checked yet

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• cites [19] sourceNot checked yet

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Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes are characteristic of TPP.

“Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes are characteristic of TPP.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Factors such as high-carbohydrate meal, exercise, steroid, and stress can precipitate an attack of TPP.

“Factors like high-carbohydrate meal exercise, steroid, and stress can precipitate an attack of TPP.”

May combine two claims.

Paralytic attacks occur only during recovery from exercise, and resumption of exercise can abort an attack.

“This explains why paralytic attacks occur only during recovery from exercise and resumption of exercise can abort an attack.”

May combine two claims.

In one series, tachycardia (mean heart rate = 105 bpm) was noted at presentation and distinguished TPP patients from those with familial hypokalemic periodic paralysis.

“In one series, tachycardia (mean heart rate = 105 bpm) was noted at presentation and distinguished these patients from those with familial hypokalemic periodic paralysis [22].”

• cites [22] 2001, QJM sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

A seasonal variation has been suggested for TPP, with more frequent attacks in summer months.

“A seasonal variation has also been suggested, with more frequent attacks in summer months.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Patients with TPP may experience recurrent episodes of weakness that last from a few hours up to 72 h, with complete recovery in between the attacks.

“Patients may experience recurrent episodes of weakness that last from a few hours up to 72 h, with complete recovery in between the attacks.”

May combine two claims.

Propranolol, but not the selective beta1-blocker metoprolol, also effectively prevented recurrence of paralytic attacks or inhibited paralysis induced by a carbohydrate load.

“Propranolol, but not the selective beta1-blocker metoprolol, also effectively prevented recurrence of paralytic attacks or inhibited paralysis induced by a carbohydrate load.”

• cites [46] sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

TPP has been increasingly documented in Asian and Hispanic populations in the USA.

“TPP has been increasingly documented in Asian and Hispanic populations in the USA.”

May combine two claims.

Using Wayne's index, only 17% of TPP patients had toxic thyrotoxicosis (score > 19), supporting the notion that most TPP patients have equivocal symptoms.

“Using the Wayne's index, a reliable quantitative score of hyperthyroid severity, it was found that only 17% of TPP patients had toxic thyrotoxicosis (score > 19), supporting the notion that most TPP patients have equivocal symptoms [24].”

• cites [24] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Exceptional cases of bulbar weakness and respiratory weakness requiring ventilatory support have been reported in TPP.

“Exceptional cases of bulbar weakness and respiratory weakness requiring ventilatory support have been reported in TPP [23].”

• cites [23] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

The complication of rhabdomyolysis may occur in a severe attack of TPP.

“The complication of rhabdomyolysis may occur in a severe attack.”

Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

Increased awareness among physicians about TPP will result in early diagnosis, appropriate treatment, and the prevention of rebound hyperkalemia.

“Increased awareness among physicians about this disorder will result in early diagnosis, appropriate treatment, and the prevention of rebound hyperkalemia.”

May combine two claims.

During an attack of paralysis or weakness in TPP, serum potassium level is usually less than 3.0 mmol/liter and can be as low as 1.1 mmol/liter.

“During an attack of paralysis or weakness serum, potassium level is usually less than 3.0 mmol/liter and can be as low as 1.1 mmol/liter.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Nonspecific beta-adrenergic blockers like propranolol have been proposed as an alternative treatment to ameliorate the paralysis without rebound hyperkalemia and raise the serum levels of potassium and phosphate.

“Nonspecific beta-adrenergic blockers like propranolol have also been proposed as an alternative treatment to ameliorate the paralysis without rebound hyperkalemia and raise the serum levels of potassium and phosphate.”

May combine two claims.

In contrast to familial hypokalemic PP, carbonic anhydrase inhibitors have not been shown to be of benefit in thyrotoxic PP and may even increase the frequency of attacks.

“In contrast to familial hypokalemic PP, carbonic anhydrase inhibitors have not been shown to be of benefit in thyrotoxic PP and may even increase the frequency of attacks [47].”

• cites [47] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Traditionally, patients with TPP are given intravenous or oral potassium to hasten muscle recovery and prevent cardiopulmonary complications; however, there is a danger of rebound hyperkalemia due to release of potassium and phosphate from the cells on recovery.

“Traditionally, patients are given intravenous or oral potassium to hasten muscle recovery and prevent cardiopulmonary complications; however, there is a danger of rebound hyperkalemia due to release of potassium and phosphate from the cells on recovery.”

May combine two claims.

In addition to hypokalemia, there may be hypophosphatemia and hypomagnesemia in TPP.

“In addition to hypokalemia, there may be hypophosphatemia and hypomagnesemia.”

May combine two claims.

Rebound hyperkalemia occurred in approximately 40% of patients with TPP, especially if they received >90 mEq of potassium chloride within the first 24 hours.

“Rebound hyperkalemia occurred in approximately 40% of patients with TPP, especially if they received >90 mEq of potassium chloride within the first 24 hours.”

May combine two claims.

Most patients with TPP have only mildly elevated serum thyroid hormone levels, and only about 10% may have mild thyrotoxic symptoms.

“Most patients with TPP have only mildly elevated serum thyroid hormone levels and only about 10% of patients may have mild thyrotoxic symptoms [6].”

• cites [6] 1996, QJM sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Although the majority of cases of thyrotoxicosis associated with TPP are due to Graves' disease, TPP can appear with thyrotoxicosis of any origin.

“Although the majority of cases of thyrotoxicosis associated with TPP are due to Graves' disease, TPP can appear with thyrotoxicosis of any origin.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Decreased muscle tone with hyporeflexia or areflexia is typical in TPP, although normal or hyperactive reflexes may be seen in some cases.

“Decreased muscle tone with hyporeflexia or areflexia is typical, although normal or hyperactive reflexes may be seen in some cases.”

Probably not a substantial claim: may not pass S4 (based).

Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes clinches the diagnosis of TPP.

“Biochemical hyperthyroidism with normal urinary potassium excretion and ECG changes clinches to diagnosis of TPP.”

May combine two claims.

Other electrocardiographic abnormalities in TPP include atrioventricular block, atrial fibrillation, ventricular fibrillation, and asystole.

“Other electrocardiographic abnormalities include atrioventricular block, atrial fibrillation, ventricular fibrillation, and asystole [40, 41].”

• cites [40] sourceNot checked yet

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• cites [41] sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Occasionally, if the patient is at the recovery stage of the paralysis, serum potassium can be normal.

“Occasionally if the patient is at the recovery stage of the paralysis, serum potassium can be normal.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Mild to moderate hypophosphatemia in the range of 0.36-0.77 mmol/liter has been reported in two thirds of TPP cases.

“Mild to moderate hypophosphatemia in the range of 0.36–0.77 mmol/liter has been reported in two thirds of cases [39].”

• cites [39] sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Precipitating factors for TPP include high carbohydrate loads, strenuous exercise, trauma, acute URI, high-salt diet, emotional stress, exposure to cold, alcohol ingestion, menstruation, and use of drugs such as corticosteroids, epinephrine, acetazolamide, and nonsteroidal anti-inflammatory drugs.

“Precipitating factors include high carbohydrate loads, strenuous exercise, trauma, acute URI, high-salt diet, emotional stress, exposure to cold, alcohol ingestion, menstruation, and use of drugs such as corticosteroids, epinephrine, acetazolamide, and nonsteroidal anti-inflammatory drugs.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Workup for other causes of hypokalemia includes urinary potassium excretion (>30 mEq indicates urinary loss), arterial blood gas for acidosis, and urinary potassium to creatinine ratio, which is <13 in TPP.

“Workup for other causes of hypokalemia include urinary potassium excretion (>30 mEq indicates urinary loss), arterial blood gas for acidosis, urinary potassium to creatinine ratio which is <13 in TPP.”

May combine two claims.

A high carbohydrate or strenuous exercise was identified as precipitant in only 12% and 7% of TPP patients, respectively.

“A high carbohydrate or strenuous exercise was identified as precipitant in only 12 and 7%, respectively.”

• cites [24] sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

The muscles affected in TPP may be asymmetrical, and bowel and bladder function are never affected.

“The muscles affected may be asymmetrical and bowel and bladder function are never affected.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Sensory function is not affected in TPP.

“Sensory function is not affected.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Attacks in thyrotoxic PP may be precipitated by events that are associated with an increased release of epinephrine or insulin, both of which cause movement of potassium into cells and low potassium blood levels.

“As with hypokalemic PP, attacks in thyrotoxic PP may be precipitated by events that are associated with an increased release of epinephrine or insulin, both of which cause movement of potassium into cells and low potassium blood levels.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

Although attacks of weakness may occur at any time of the day, a high frequency of attacks at night or early in the morning has been reported in TPP.

“Although attacks of weakness may occur at any time of the day, a high frequency of attacks at night or early in the morning has been reported in TPP.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Serum creatine phosphokinase of muscle origin is elevated in about two thirds of TPP patients, particularly among those whose attacks are precipitated by exercise.

“Serum creatine phosphokinase of muscle origin is elevated in about two thirds of patients, particularly among those whose attacks are precipitated by exercise.”