Q J Med 2003; 96: 611-613
© 2003 Association of Physicians
Correspondence |
Hypokalaemic thyrotoxic periodic paralysis in the UK
Sir,I read with interest the article ‘Severe hypokalaemia in a Chinese male’ by Lin et al.1 In Western countries, most cases of hypokalaemic periodic paralysis (HPP) are due to autosomal dominant familial periodic paralysis (FPP), but in an Asian population, thyrotoxic periodic paralysis (TPP) is the most common cause.1–5 The age of onset, race, family history, medications and underlying disease states can help in identifying the cause of HPP.6 Initial therapy of the patient with HPP includes potassium (K+) replacement and search for underlying aetiology. Further management depends on the aetiology of hypokalaemia.6 TPP is common in Asian and Hispanic individuals, and uncommon in Whites and Afro-Americans.1–5,8,9 As patients of Oriental ethnicity are now frequently encountered in the Western world, TPP should be included in the differential diagnosis of muscle weakness in the Emergency department, in order to avoid life-threatening complications such as hypokalaemia and thyrotoxicosis, particularly in the UK with its ethnic Chinese population in the big cities.
In October 2002, a 30-year old Vietnamese man of Chinese parentage presented to the Emergency department in the early hours of the morning complaining of sudden generalized weakness in all four limbs. The previous day he started work in his ‘take-away’ restaurant at around 11 am and had worked until 8 pm. He then had a substantial meal of carbohydrate-rich food and went to bed at around midnight. He had no significant past or family history. He had a tachycardia of 100 bpm, and his blood pressure was 119/85. Physical examination revealed a diffusely enlarged palpable thyroid gland. He was fully alert and coherent. Motor power in all the four limbs was 2/5 grade. He was totally areflexic,6 with both plantars down-going. He was clinically euthyroid. His initial serum K+ was 1.2 mmol/l (3.5–4.8), with normal renal function, calcium, glucose and liver function tests. Serum creatinine phosphokinase (CK) level was 1099 IU/l (NR 38–148).12 Blood pH was 7.44. Hb%, white blood cell count, platelets, ESR and C-reactive proteins were all normal.
Emergency treatment was begun with prompt intravenous administration of potassium chloride (80 mmol over 90 min). The patient felt normal almost within 15 min. The K+ was stopped once serum K+ was 4.2, and he was kept on oral spironolactone 100 mg/day.4 His subsequent serum K+ remained within normal range, showing no rebound rise.7 Urine electrolytes in 24-h urine (volume 4.26 l) were within normal range. His free thyroxine (FT4) level was 73 pmol/l (NR 7–17) and TSH level was 0.02 mU/l (NR 0.35–2.75). Anti-thyroid peroxidase (TPO) antibodies17 were 439 IU/ml (NR 0–35), later rising to 723 IU/ml. Prolactin was 129 mI/l (NR 0–190). Electrocardiogram showed mild tachycardia of 100 bpm and U-waves in lead II, III, VI--V6.6 Ultrasound examination of the thyroid gland revealed mild enlargement of the thyroid gland with diffuse parenchymal disease. Chest X-ray was normal. Human leukocyte antigen (HLA) type was A11, A33; B15, B58; DR3; DQ2, DQ1. After 24 h of monitoring his FT4, he was started on carbimazole and the beta-blocker propronolol.1,5,16 Spironolactone was discontinued before his discharge on the seventh day. He has been followed-up regularly since. He has remained well without any overt signs of physical weakness or thyrotoxicosis. It took nearly 14 weeks before he became biochemically euthyroid. The plan is for a long-term close follow-up.
This patient had Graves’ disease with hypokalaemic paralysis. He was clinically euthyroid, but had a palpable goitre which prompted us to check his thyroid status. His blood pressure was never very high as reported elsewhere.9 He recovered quickly with K+ replacement. He was given a much larger dose of i.v. K+ than the recommended 10 mmol/h,9 but fortunately did not show any rebound rise.7 Although rare, this case is significant because if hyperthyroidism is not diagnosed and treated, TPP is likely to recur. This patient had a palpable goitre, as has been reported before,9 but many reported cases did not have clinical features of thyrotoxicosis or palpable goitre.2 The Asian experience suggests that the hyperthyroidism is usually obvious, although this has not been supported in another study.11 Laboratory findings include low serum potassium and elevated serum creatine phosphokinase;12 electrocardiographic changes of hypokalaemia may be present,6 and thyroid function studies are abnormal.
A total of 2% of thyrotoxic patients in China and Japan were reported to have this complication,4 but it has also been recognized in Thai, Filipino, Vietnamese, Korean and Malay populations.11 In the US, the incidence of TPP in a non-Asian ethnic population is approximately one-tenth that found in Asian countries, but also has a male predominance.10
TPP is characterized by sudden transient recurrent episodes of painless weakness or paralysis without alteration in consciousness or sensation, usually occurring after heavy exertion or a high-carbohydrate meal, followed by a prolonged rest.9 The diurnal variation in K+ movement, where there is nocturnal K+ influx into the muscles, would explain the tendency for TPP to occur at night.13 A heavy day’s work followed by a carbohydrate-rich meal probably precipitated the attack in this case. The principal clinical difference between FPP and TPP is the presence of thyrotoxicosis in the latter and the lack of positive family history, although familial TPP has been reported.4 Deep tendon reflexes are depressed in most patients.6 Respiratory muscles are usually, but not always, spared.6 Recovery can be spontaneous after 3–36 h, and may be hastened by K+ administration. The onset of paralytic attacks in FPP is often during adolescence, whereas in the majority of reports, TPP begins at 20–40 years of age.4 The male:female ratio in TPP is 20:1.4 Recently a rare case of TPP with hypokalaemia was described in a White woman.14
The pathophysiology of TPP is not well understood. The thyroid hormone directly stimulates the Na+-K+-ATPase dependent K+ channel and increases the catecholamine-mediated intracellular potassium shift,1,5,7 which is also stimulated by insulin1,9 (as a result of high carbohydrate intake). Direct measures of serum of catecholamines and their urinary metabolites show values that are equal to or less than normal in hyperthyroid state.15 However, beta-blockers are very useful in TPP associated with hypokalaemia.1,5,16 The male predominance and the racial differences in TPP with hypokalaemia are puzzling.14 Differences in HLA subtypes in different racial groups have been widely studied: Japanese (DRw 8), Singapore Chinese (A2BW22, AW19B17) and Hong Kong Chinese (B5, BW46) all have different HLA subtypes.9 HLA DRw8 makes the Japanese susceptible to TPP, and yet the same HLA in Caucasians makes them susceptible to Graves’ disease.19 Genetic mutations in the control of Na+-K+-ATPase activity within the same HLA subtype may explain the ethnic difference. Like FPP, a genetic mutation in TPP has recently been described in the K+ ionic channel gene KCNE3.17
The patient also had a high titre of anti-TPO autoantibody; 85–90% of patients with Graves’ disease have anti-TPO autoantibodies.18 This case shows that in the ethnically Chinese or other Oriental populations living in Britain, HPP may be caused by thyrotoxicosis, and that thyroid function studies are needed to confirm or deny this diagnosis.
-->
Department of Medicine
Tameside General Hospital
Ashton-under-Lyne
e-mail: ranjitsinharay{at}hotmail.com
References
1. Lin YF, Lin SH, Tsai WS, David MR, Halperin ML. Severe hypokalaemia in a Chinese male. Q J Med 2002; 95: 695–704.
2. Ober KP. Thyrotoxic periodic paralysis in the United States:report of 7 cases and review of the literature. Medicine 1992; 71:109–20.[Medline]
3. Ko GTC, Chow CC, Yeung VTF, Chan HHL, Li JKY, Cockram CS. Thyrotoxic periodic paralysis in a Chinese population. Q J Med 1996; 89:463–8.
4. McFadzean AJS, Yeung R. Periodic paralysis complicating thyrotoxicisis in Chinese. Br Med J 1967; 1:451–5.
5. Lin SH, Lin YF, Halperin ML. Hypokalaemia and paralysis. Q J Med 2001; 94:133–9.[Web of Science]
6. Ahlawat SK, Sachdev A. Hypokalaemic paralysis. Postgrad Med J 1999; 75:193–7.
7. Manoukain MA, Foote JA, Crapo LM. Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes. Arch Intern Med 1999; 159:601–6.
8. Zumo LA, Terzian C, Brannan T. Thyrotoxic hypokalaemic periodic paralysis in a Hispanic male. J Natl Med Assoc 2002; 94:383–6.[Medline]
9. Salifu MO, Otah K, Carroll HJ, Ifudu O, Friedman EA, Oh MS. Thyrotoxic hypokalaemic paralysis in a Black man. Q J Med 2001; 94:659–60.
10. Kelley DE, Gharib H, Kennedy FP, Duda R, McManis P. Thyrotoxic periodic paralysis. Report of 10 cases and review of electromyographic data. Arch Intern Med 1989; 149:2597–600.
11. Goh SH. Thyrotoxic periodic paralysis: reports of seven patients presenting with weakness in an Asian emergency department. Emerg Med J 2002; 19:78–9.
12. Kusakabe T, Yoshiba M, Nishikawa M. Thyrotoxic periodic paralysis:peculiar case with unusual dystonic behavior and variable relations of paralysis to serum potassium levels. J Clin Endocrinol Metab 1976; 43:730–40.
13. Charness ME, Johns RJ. Hypokalemic periodic paralysis. Johns Hopkins Med J 1978; 143:148–53.[Web of Science][Medline]
14. Dixon AN, Jones R. Thyrotoxic periodic paralysis in a white woman. Postgrad Med J 2002; 78:687–8.
15. Levey GS, Klein I. Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism. Am J Med 1990; 88:642–6.[CrossRef][Web of Science][Medline]
16. Conway MJ, Seibel JA, Eaton P. Thyrotoxicosis and periodic paralysis:improved with beta blockade. Ann Intern Med 1974; 81:332–6.
17. Da Silva MRD, Cerutti JM, Arnaldi LAT, Maciel RMB. A Mutation in the KCNE3 Potassium Channel Gene Is Associated with Susceptibility to Thyrotoxic Hypokalaemic Periodic Paralysis. J Clin Endocrinol Metab 2002; 87:4881–4.
18. Kotani T. anti-TPO autoantibodies. Rinsho Byori 1998; 46:324–30.[Medline]
19. Lazarus JH. Hyperthyroidism. Lancet 1997; 349:339–43.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||