In our study, nine of 52 (17.3%) patients with HPP had TPP, and two-thirds of them had subclinical thyrotoxicosis/hyperthyroidism. The demographic and clinical variables as well as rebound hyperkalemia were not statistically different between the TPP and the IHPP groups. TPP is thought to be common in Oriental Asian males. It has been reported mainly from China, Japan, Korea, Taiwan and Singapore.[2
] The incidence of TPP in these regions ranges between 8% and 13% in males and 0.2% and 0.4% in females. Thyrotoxicosis however is common in females, but TPP in more common in males. The male to female ratio varies from 17:1 to 20:1 in Japan, 33:1 to 48:1 in the USA and 44:1 to 76:1 in China.[2
] This figure is 8:1 in our study. A lower male to female ratio in our study may be because of the small sample size or difference in ethnicity. The commonness of TPP in males may be due to the influence of androgen in potassium homeostasis. Association of TPP in two patients with adrenal adenoma having hyperandrogenemia has been reported. It was postulated that androgen may have triggered TPP by inducing sodium potassium ATPase activity.[13
] TPP has also been reported from western countries, especially in American Indians and Hispanics.[4
] These reports are attributed to migration of the oriental population. From India, the present report is the largest series on TPP.
TPP commonly occurs in the age group of 20–40 years; the mean age of our patients is also 33.6 (24–48) years.[2
] Patients with TPP have variable weakness, which may be precipitated by high carbohydrate meal, physical exertion, preceding febrile illness and, often, on getting up from the sleep, similar to patients with IHPP.[16
] In the present study, heavy carbohydrate meal and febrile illness were the precipitating factors in the TPP group, while heavy exercise and alcohol were the precipitating factors in the IHPP group. Seasonal variation of TPP attacks has been reported from China and in few other studies.[2
] It has been attributed to increased consumption of sweet drinks, outdoor activities, exercise and increased potassium loss in sweat during the summer months. In our study, most of the patients with TPP were also admitted during the spring and summer months. Bulbar weakness in TPP has not been reported, although acute bulbar paralysis in the patients with thyrotoxicosis has reported in some patients who improved over weeks following treatment of thyrotoxicosis but not following potassium infusion.[17
] Both our patients with bulbar weakness however improved completely after potassium infusion along with the improvement in limb power, suggesting a relationship of bulbar weakness and hypokalemia. Acute respiratory failure in a 29-year-old male with TPP has been reported, whose plasma potassium was 3 mmol/L. He improved following potassium infusion and was weaned from the ventilator after 14 h.[19
] Bulbar weakness and respiratory paralysis have also been reported in a patient with severe HPP due to renal tubular acidosis. His neurological conditions improved following correction of potassium.[20
] Two of our patients with TPP had respiratory compromise, but did not require artificial ventilation. The serum potassium level in our TPP group was lower than in the IHPP group. In TPP, there is a shift of potassium ion into the cells rather than loss of potassium.[6
] This may result in very low serum potassium and may produce life-threatening paralysis and cardiac arrhythmias. Serum phosphorus also may be reduced during the attack, and was low in seven of our patients.[21
] Patients with TPP may be confused with GB syndrome, renal tubular acidosis and IHPP. In our study, one patient was inadvertently diagnosed as GB syndrome and was treated with IVIg by the primary physician and another with acetazolamide for prophylaxis of suspected IHPP. Acetazolamide aggravates muscle weakness in patients with TPP. The comparison of TPP and IHPP in a study revealed that patients with IHPP presenting before the age of 20 years may have a family history and that serum potassium levels are not very low.[22
] Severe hypokalemia in periodic paralysis suggests an underlying secondary cause.[10
] In our study, the demographic and clinical features were not significantly different in both the groups, except serum potassium, which was lower in the TPP group compared with the IHPP group.
The thyrotoxic symptoms may be absent at the time of attack of TPP in 10–25% of the patients.[5
] In our study, two-thirds of the patients with TPP had subclinical thyrotoxicosis/hyperthyroidism at the time of presentation. This makes diagnosis of TPP more challenging. A high index of suspicion is needed for the diagnosis of TPP, especially in a young to middle aged male of Asian ethnicity who develops hypokalemia and paralysis. Occurrence and severity of TPP does not depend on severity and etiology of thyrotoxicosis.[12
] In our study, the cause of thyrotoxicosis could be ascertained in seven patients, which were toxic nodular goiter, Grave's disease, diffuse toxic goiter, colloid goiter and thyroiditis. Etiology of hyperthyroidism could not be determined in two of our patients.
Treatment of TPP is oral or intravenous potassium supplementation, depending on the severity of weakness and to prevent recurrence. Nonselective beta blockers and correction of thyrotoxicosis are recommended. Rebound hyperkalemia has been reported in TPP and sporadic HPP during treatment. Fatal cardiac arrhythmia has been reported secondary to rebound hyperkalemia in TPP.[23
] It is important to monitor the serum potassium during treatment to avoid such complications. In our study, three patients with TPP and eight with IHPP had rebound hyperkalemia. None of the patients however had complications of rebound hyperkalemia. In our patients, propranolol and neomarcazole were prescribed to all. Radioactive iodine or surgery was performed later depending on the severity of the thyrotoxicosis and patient preference. Correction of thyrotoxicosis is important for preventing the recurrent attacks of paralysis. The limitations of the present study are its retrospective nature, having been performed in a neurology setting and long-term follow-up not being available.