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Disease Profile

Thyrotoxic periodic paralysis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Adult

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ICD-10

G72.3

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Categories

Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 79102

Definition
Thyrotoxic periodic paralysis (TPP) is a rare neurological disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state.

Epidemiology
It is most common in Asian males (with male-to-female ratios ranging from 17:1 to 70:1) during the third decade of life: the annual incidence in Chinese and Japanese thyrotoxicosis patients is estimated at around 1/50, whereas it is estimated at 1-2/1,000 among non-Asian thyrotoxicosis patients.

Clinical description
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.

Etiology
The pathogenesis remains unclear. Genetic predisposition is thought to play a role in the pathogenesis of TPP and single nucleotide polymorphisms (SNPs) of the CACNA1S (1q32) and GABRA3 (Xq28) genes have been associated with TPP susceptibility in some Asian populations. Hypokalemia is the consequence of an extrato intracellular potassium shift due to an increase in Na/K-ATPase pump activity, either as a direct response to thyroid hormone or indirectly via adrenergic stimulation, insulin or exercise.

Diagnostic methods
Biochemical studies are essential for diagnosis, with mild-to-severe thyrotoxicosis and hypokalemia during attacks being the major findings. Other anomalies may include hypophosphatemia and hypomagnesemia, without changes in acid-base balance. EMG reveals myopathic changes during attacks and muscle excitability anomalies after a prolonged exercise test. ECG anomalies are also noted. Thyrotoxicosis is the key finding for distinguishing TPP from other causes of hypokalemic periodic paralysis (HOP), such as familial HOP (FHOP; see this term), and from other hypokalemic disorders with a transcellular potassium shift, and excessive renal potassium wasting or gastrointestinal losses.

Differential diagnosis
The differential diagnosis may also include Guillain-Barré syndrome, transverse myelitis (see these terms), spinal cord compression and hysteria, as well as muscle weakness and fatigue associated with hyperthyroidism in patients with thyrotoxic myopathy or myasthenia gravis (see this term).

Genetic counseling
TPP usually occurs sporadically

Management and treatment
Management of TPP includes definitive control of hyperthyroidism, prevention of attacks with propranolol and avoidance of precipitating factors. Potassium administration during attacks may prevent cardiac arrhythmias and hasten the recovery from paralysis.

Prognosis
The prognosis for patients is good and TPP resolves when euthyroid status is achieved.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
100% of people have these symptoms
Episodic hypokalemia
Recurrent low potassium
0012726
Periodic hypokalemic paresis
0008153
80%-99% of people have these symptoms
Decreased urinary potassium
0012364
EMG abnormality
0003457
Episodic flaccid weakness
0003752
Graves disease
0100647
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hypomagnesemia
Low blood magnesium levels
0002917
Increased intramyocellular lipid droplets
0012240
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Mildly elevated creatine kinase
0008180
Obesity
Having too much body fat
0001513
Palpitations
Missed heart beat
Skipped heart beat

[ more ]

0001962
Tetraplegia
Paralysis of all four limbs
0002445
Thyrotoxicosis with toxic multinodular goiter
0011785
Thyrotoxicosis with toxic single thyroid nodule
0011786
Transient hypophosphatemia
0008285
30%-79% of people have these symptoms
Constipation
0002019
Exercise-induced muscle fatigue
0009020
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Muscle spasm
0003394
Muscle stiffness
0003552
Postprandial hyperglycemia
0011998
Rhabdomyolysis
Breakdown of skeletal muscle
0003201
Tremor
0001337
Urinary retention
0000016
Weight loss
0001824
5%-29% of people have these symptoms
Late-onset proximal muscle weakness
0003694
Prolonged QT interval
0001657
Second degree atrioventricular block
0011706
Shortened PR interval
0005165
Ventricular fibrillation
0001663
1%-4% of people have these symptoms
Hyperkalemia
Elevated serum potassium levels
0002153
Ophthalmoparesis
Weakness of muscles controlling eye movement
0000597
Respiratory paralysis
0002203
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Goiter
Enlarged thyroid gland in neck
0000853
Hyperthyroidism
Overactive thyroid
0000836
Hypokalemia
Low blood potassium levels
0002900
Muscle weakness
Muscular weakness
0001324
Periodic paralysis
0003768
Sporadic
No previous family history
0003745
Tachycardia
Fast heart rate
Heart racing
Racing heart

[ more ]

0001649

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Thyrotoxic periodic paralysis. Click on the link to view a sample search on this topic.