Novel etiopathophysiological aspects of thyrotoxic periodic paralysis

Abstract

Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and is the most common cause of acquired periodic paralysis. Typically, paralytic attacks cease when hyperthyroidism is abolished, and recur if hyperthyroidism returns. TPP is often underdiagnosed, as it has diverse periodicity, duration and intensity. The age at which patients develop TPP closely follows the age at which thyrotoxicosis occurs. All ethnicities can be affected, but TPP is most prevalent in people of Asian and, secondly, Latin American descent. TPP is characterized by hypokalemia, suppressed TSH levels and increased levels of thyroid hormones. Nonselective β adrenergic blockers, such as propranolol, are an efficient adjuvant to antithyroid drugs to prevent paralysis; however, an early and definitive treatment should always be pursued. Evidence indicates that TPP results from the combination of genetic susceptibility, thyrotoxicosis and environmental factors (such as a high-carbohydrate diet). We believe that excess T(3) modifies the insulin sensitivity of skeletal muscle and pancreatic β cells and thus alters potassium homeostasis, but only leads to a depolarization-induced acute loss of muscle excitability in patients with inherited ion channel mutations. An integrated etiopathophysiological model is proposed based on molecular findings and knowledge gained from long-term follow-up of patients with TPP.

Mechanism of Thyrotoxic Periodic Paralysis

“…Sympathetic stimulation of insulin release in pancreas b-cells provides additional rationale for using nonselective b-blockers to treat acute hypokalemia and paralytic attack of TPP. 5,9 TPP is also known to occur predominately among males despite a higher incidence of thyrotoxicosis in women, suggesting the potential role of androgen on Na + -K + ATPase activity. Although more work needs to be done in this area, androgens may increase Na + -K + ATPase activity through androgen receptor 10 and hyperadrenergic state.…”

Thyrotoxic Periodic Paralysis in a 20-Year-Old Nigerian Male

“…Evidence suggests that TPP results from a combination of factors such as genetic, environmental, and thyrotoxicosis [17] the interaction of these factors would alter the channel dynamics of the cell membrane at the neuromuscular junction, triggering the paralysis crises only in patients genetically susceptible [18]. The genetic factors could include a defect in one of the ion channels involved in excitation contraction coupling (Ca2+, Na+, and K+) or a defect in one of the channel's regulatory subunits.…”

Thyrotoxic periodic paralysis- A case report

“…3 Differential diagnosis of TPP includes familial hypokalemic periodic paralysis, Guillain-Barré syndrome and other causes of proximal myopathy ( Table I). 5 Various factors are involved in pathogenesis of TPP including genetic, environmental and acquired factors. 4 The genetic factors could include a defect in one of the ion channels involved in excitation-contraction coupling (Ca 2+ , Na + , and K + ) or a defect in one of the The diagnosis of TPP is mainly based on biochemical parameters.…”

“…In the Chinese, TPP occurs in 13% of male and 0.17% of female thyrotoxic patients, in a series published in 1967. The male to female ratio ranges from 17: 1 to 70: 1 despite the fact that hyperthyroidism is more common in females (female-to-Journal of International Medicine and Dentistry 2017;4(1): [1][2][3][4][5] male ratio of 9: 1). 2 We report the clinical and laboratory findings in a patient with TPP without associated symptoms of thyrotoxicosis.…”