Mechanism of Thyrotoxic Periodic Paralysis
Open accessAbstract
The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na(+)-K(+) ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. This mechanism alone, however, cannot adequately explain how hypokalemia occurs during acute attacks or the associated paradoxical depolarization of the resting membrane potential. Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K(+) (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K(+) efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na(+) channels and causes muscle unexcitability and paralysis.
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The dual hits of increased intracellular K+ influx from activated Na+, K+-ATPase and decreased K+ efflux from defective Kir channels potentiates the serum hypokalemia that upsets membrane polarization and muscle excitability in TPP.
“The dual hits of increased intracellular K+ influx from activated Na+, K+-ATPase and decreased K+ efflux from defective Kir channels potentiates the serum hypokalemia that upsets membrane polarization and muscle excitability in TPP (46).”
From A 10-year analysis of thyrotoxic periodic paralysis in 135 patients: focus on symptomatology and precipitants (2013) · cites this paper as [46]
Reduced basal muscular Kir current may also be an important mechanism of TPP.
“These findings also suggest that reduced basal muscular Kir current may also be an important mechanism of TPP (46).”
From A 10-year analysis of thyrotoxic periodic paralysis in 135 patients: focus on symptomatology and precipitants (2013) · cites this paper as [46]
Recent studies support that genetic loss-of-function mutations in inward rectifying potassium channels are associated with TPP.
“Recent studies have supported the genetic loss of function mutations in inward rectifying potassium channels associated with TPP.”
From A Case of Thyrotoxic Periodic Paralysis: "I Can't Move!" (2023) · cites this paper as [8]
Thyrotoxic periodic paralysis is characterized by a thyroid hormone-induced intracellular shift of potassium, leading to muscle weakness and paralysis.
“Thyrotoxic periodic paralysis is characterized by a thyroid hormone-induced intracellular shift of potassium, leading to muscle weakness and paralysis.”
From A Case of Thyrotoxic Periodic Paralysis: "I Can't Move!" (2023) · cites this paper as [8]
Increased Na-K ATPase activity, coupled with genetic mutations, can lead to a cycle of extreme hypokalemia in periodic paralysis.
“This, coupled with increased Na-K ATPase activity, can lead to a cycle of extreme hypokalemia, as seen in periodic paralysis [8].”
From A Case of Thyrotoxic Periodic Paralysis: "I Can't Move!" (2023) · cites this paper as [8]
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“This, coupled with increased Na-K ATPase activity, can lead to a cycle of extreme hypokalemia, as seen in periodic paralysis [8].”
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- Authors
- Lin, S.-H., & Huang, C.-L.
- Affiliations
- Tri-Service General Hospital (TW)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Lin, Shih-Hua
- ORCID
- Lin, Shih-Hua
- Venue
- Journal of the American Society of Nephrology
- Published
- 2012-06
- Volume
- 23
- Issue
- 6
- Pages
- 985-988
- ISSN
- 1046-6673 (ISSN-L)
- PMC
- PMC3358768
- OpenAlex
- W2097464324
- Cited by
- 174
- References
- 17
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 20 · 2023: 18 · 2022: 18 · 2021: 12 · 2020: 14 · 2019: 5 · 2018: 9 · 2017: 11 · 2016: 8 · 2015: 9 · 2014: 13 · 2013: 10 · 2012: 2
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation pour la Recherche Médicale
- Tri-Service General Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
- Keywords
- thyrotoxic periodic paralysis, hypokalemia, inwardly rectifying potassium channels, skeletal muscle, Na+/K+-ATPase, hyperinsulinemia, resting membrane potential, thyroid hormones
- MeSH terms
- Kcnj10 Channel, Sodium-Potassium-Exchanging ATPase, Female, Humans, Male, Membrane Potentials, Potassium, Prognosis, Severity of Illness Index, Thyroid Function Tests, Thyroid Hormones, Thyrotoxicosis, Treatment Outcome, Risk Assessment, Hypokalemic Periodic Paralysis, Potassium Channels, Inwardly Rectifying
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