Mechanism of Thyrotoxic Periodic Paralysis

Abstract

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.

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

“…In addition, several other studies have demonstrated that the activity of the Na+/K+-ATPase pump is increased in thyrotoxicosis and is more exacerbated in patients with TPP [21,22]. The hypokalemia observed in these cases is due to the increased K + influx into a cell secondary to the increase in the activity of the Na+/K+-ATPase pump and by the hyperinsulinemic response to carbohydrate intake in patients susceptible to TPP [23,24]. Androgens also can increase the activity of the Na+/K+-ATPase pump, which explains the higher incidence of the disease in young males [24].…”

Paralisia periódica hipocalêmica tireotóxica em paciente de ascendência africana

“…Sobre a fisiopatologia da PPHT, é possível que o excesso de hormônios tireoidianos, a estimulação β2-adrenérgica e a hiperinsulinemia estimulem a bomba de sódio/potássio ATPase, localizada nas membranas celulares dos músculos esqueléticos, resultando em transporte de potássio para o compartimento intracelular, com consequente hipocalemia e alterações na força muscular (7,10). Entretanto, a patogênese da PPHT não é totalmente elucidada, sendo possível que haja também predisposição genética (1).…”

Iodine-induced thyrotoxic hypokalemic paralysis after ingestion ofSalicornia herbace

“…Thyroid hormone can directly stimulate Na þ /K þ adenosine triphosphatase (ATPase) activity, which results in the transcellular shift of potassium into the cells. 14,15 Hyperinsulinemia may be another important factor that provokes attacks of TPP. 16 The higher incidence of TPP in males may be explained by the fact that Na…”