What are the other Names for this Condition? (Also known as/Synonyms)

• Thyrotoxic, Hypokalemic Periodic Paralysis
• TPP (Thyrotoxic Periodic Paralysis)

What is Thyrotoxic Periodic Paralysis? (Definition/Background Information)

• Thyrotoxic Periodic Paralysis (TPP) is a rare neurological disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state
• TPP manifests as recurrent episodes of acute muscular weakness of the four extremities that vary in severity from paresis to complete paralysis
• Recovery occurs within 2-72 hours
• Attacks typically occur at night and may be preceded by muscle cramps, aches and stiffness. Ocular, bulbar and respiratory involvement has also been reported but is rare. Attacks are triggered by ingestion of a high carbohydrate load or strenuous physical activity followed by a period of rest
• Episodes only occur when patients are thyrotoxic but symptoms and classical signs of hyperthyroidism are often absent at the time of the first attack
• TPP can occur in association with any cause of hyperthyroidism, but is most commonly associated with Graves' disease

(Source: Thyrotoxic Periodic Paralysis; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Thyrotoxic Periodic Paralysis? (Age and Sex Distribution)

• Thyrotoxic Periodic Paralysis is a rare disorder
• The onset of symptoms occurs in adulthood, typically in the 20s
• Although all populations may be affected, the disorder is most common amongst Asians, occurring at a high frequency of 1:50 in individuals of Japanese and Chinese descent
• The condition can occur in both genders, although among Asians, it is more prevalent in males (male: female prevalence ratio is between 17:1 and 70:1)

What are the Risk Factors for Thyrotoxic Periodic Paralysis? (Predisposing Factors)

The risk factors for Thyrotoxic Periodic Paralysis may include:

• Being of Asian descent
• Being Asian male
• Single nucleotide polymorphisms in CACNA1S or GABRA3 gene 
• Grave’s disease

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Thyrotoxic Periodic Paralysis? (Etiology)

• The exact cause of Thyrotoxic Periodic Paralysis is not clear at the present time
• Single nucleotide polymorphisms in CACNA1S or GABRA3 gene may predispose an individual to developing this condition, as reported in some Asian populations
• Individuals with Grave’s disease, characterized by excess thyroid hormone in their system, are reported to develop Thyrotoxic Periodic Paralysis

What are the Signs and Symptoms of Thyrotoxic Periodic Paralysis?

The signs and symptoms of Thyrotoxic Periodic Paralysis may include:

• Episodic hypokalemia 
• Periodic hypokalemic paresis
• Goiter 
• Hyperthyroidism 
• Hypokalemia 
• Muscle weakness 
• Periodic paralysis 
• Sporadic

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Decreased urinary potassium 
• EMG abnormality 
• Episodic flaccid weakness 
• Graves disease 
• Hyperhidrosis
• Hypomagnesemia
• Increased intramyocellular lipid droplets 
• Lower limb muscle weakness 
• Mildly elevated creatine phosphokinase 
• Obesity 
• Palpitations
• Tetraplegia 
• Thyrotoxicosis with toxic multinodular goiter 
• Thyrotoxicosis with toxic single thyroid nodule 
• Transient hypophosphatemia

Frequently present symptoms in 30-79% of the cases:

• Constipation 
• Exercise-induced muscle fatigue 
• Hyporeflexia 
• Muscle cramps 
• Muscle stiffness 
• Postprandial hyperglycemia 
• Rhabdomyolysis 
• Tremor 
• Urinary retention 
• Weight loss

Occasionally present symptoms in 5-29% of the cases:

• Late-onset proximal muscle weakness
• Prolonged QT interval  
• Second degree atrioventricular block 
• Shortened PR interval 
• Ventricular fibrillation

1%-4% of individuals have these symptoms:

• Hyperkalemia 
• Ophthalmoparesis 
• Respiratory paralysis

(Source: Thyrotoxic Periodic Paralysis; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Thyrotoxic Periodic Paralysis Diagnosed?

Thyrotoxic Periodic Paralysis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests, including checking for levels of thyroid hormone and potassium in blood
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Thyrotoxic Periodic Paralysis?

The complications of Thyrotoxic Periodic Paralysis that is left untreated may include:

• Osteoporosis: A condition causing brittle bones
• Heart disorders such as abnormal heart rhythm and heart failure due to low levels of potassium
• Thyroid storm/crisis: It is a medical emergency that needs to be treated in a hospital. In this condition, there is a sudden worsening of the symptoms of hyperthyroidism, which may occur with an infection, and it includes abdominal pain, fever, and decreased alertness

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Thyrotoxic Periodic Paralysis Treated?

The treatment for Thyrotoxic Periodic Paralysis involves medication to allow an affected individual reach a euthyroid status. Management methods may include:

• Radioactive iodine treatment or surgery to address elevated levels of thyroid hormones
• Management of heart function abnormalities with medication (propranolol)
• Potassium administration during attacks of paralysis

How can Thyrotoxic Periodic Paralysis be Prevented?

Currently, no methods or guidelines are available for the prevention of Thyrotoxic Periodic Paralysis 

• However, the severity of the condition can be reduced by a timely diagnosis and proper treatment
• Active research is currently being performed to explore the possibilities for treatment and prevention of disorders such as Thyrotoxic Periodic Paralysis 

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Thyrotoxic Periodic Paralysis? (Outcomes/Resolutions)

• The prognosis of Thyrotoxic Periodic Paralysis is dependent upon the severity of the signs and symptoms and associated complications, if any
• With a timely diagnosis and prompt treatment, thyroid hormone levels may be brought to within the normal range. In such cases, the outcomes are positive
• The prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Thyrotoxic Periodic Paralysis:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/