Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms
- Author:
Gan QING
1
;
Wan Nur Amalina ZAKARIA
;
Fatimah Zahra Mohamad ROM
;
Wan Nor Fazila Hafizan Wan NIK
;
Hani Ajrina ZULKEFLEE
;
Siti Nadirah Ab RAHIM
Author Information
- Publication Type:Review Article
- From:Endocrinology and Metabolism 2025;40(6):821-829
- CountryRepublic of Korea
- Language:English
- Abstract: Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare but potentially fatal complication of thyrotoxicosis, characterized by transient episodes of muscle weakness in the setting of hypokalemia and underlying hyperthyroidism. Although thyrotoxicosis is more common in females, THPP predominantly affects males, especially in Asian populations, in which its prevalence is notably higher. Early recognition is essential to prevent serious complications such as cardiac arrhythmias and respiratory failure; however, THPP is frequently misdiagnosed, particularly in Western countries, due to clinical overlap with familial hypokalemic periodic paralysis. The pathophysiology of THPP involves thyroid hormone–induced upregulation of Na+/K+-ATPasease and heightened β-adrenergic sensitivity, which promote intracellular potassium shifts. Postprandial insulin surges following high carbohydrate intake further exacerbate this effect. Genetic susceptibility, including human leukocyte antigen haplotypes and mutations in ion channel genes (e.g., KCNE3, CACNA1S, SCN4A, and KCNJ18), plays a critical role. The resulting hypokalemia leads to hyperpolarization of muscle membranes, impairing excitability and causing paralysis. Structural muscle changes, such as sarcoplasmic reticulum proliferation and sodium channel dysfunction, may also contribute to THPP. Electrolyte abnormalities, including hypophosphatemia, hypomagnesemia, and hypocalcemia, are common due to transcellular shifts. This review underscores the importance of understanding the hormonal, genetic, and cellular mechanisms underlying THPP to enhance diagnostic accuracy and guide effective treatment strategies.
