CASE REPORT

In October 2002, a 30 year old Vietnamese of Chinese parentage presented in the early hours of one morning complaining of sudden generalised weakness. The previous day he had worked hard in his “take away” restaurant. He then had a carbohydrate rich meal at around 8 pm and went to bed at around 12 midnight. He had no significant medical or family history.

He had a tachycardia of 100/min and his blood pressure was 119/85. He was fully alert and coherent. His motor power was reduced. He was totally areflexic with both plantars downgoing. 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. His serum creatinine phosphokinase concentration was 1099 IU/l (38–148). His blood pH was 7.44. His Hb%, white blood cell count, platelets, erythrocyte sedimentation rate, and C reactive proteins were all normal.

Treatment was started with intravenous administration of K⁺ of 80 mmol over 90 minutes. Once the serum K⁺ reached 4.2 his weakness disappeared. His subsequent serum K⁺ remained normal. His urine electrolytes in 24 hours’ urine were within normal range. His free thyroxine (FT4) level was 73 pmol/l (7–17), and the TSH level was 0.02 mu/l (0.35–2.75). Anti-thyroid peroxidase antibodies were 439 IU/ml (0.0–35) on admission, which later was increased to 723 IU/ml. Electrocardiogram showed mild tachycardia of 100/min and U-waves in lead II, III, VI–V6.

Ultrasound examination of the thyroid gland showed mild enlargement of the thyroid gland with diffuse parenchymal disease. He was found to have the following human leucocyte antigen (HLA) sub-type: A11, A33; B15, B58; DR3; DQ2, DQ1.

He was given a carbimazole and β blocker combination. In three weeks his FT4 came down to 35 pmol/l. He became biochemically euthyroid by the end of the 14th week. He has remained hypokalaemic weakness free ever since.

DISCUSSION

This patient has Graves’ disease with hypokalaemic paralysis. He recovered quickly with K⁺ replacement. He was given a much larger dose of intravenous K⁺, instead of the recommended 10 mmol/h,⁵ but fortunately did not show any rebound rise.⁴

Many reported cases of TPP did not have clinical features of thyrotoxicosis.⁵ However, in the Asian patients hyperthyroidism were always obvious, although this has been disputed recently in another study.⁹ A total of 2% of thyrotoxic patients in China and Japan were reported to have TPP,² but it has also been recognised in the Thai, Vietnamese, Korean, and Malay populations.⁹

TPP is characterised by sudden transient recurrent episodes of painless paralysis usually occurring after heavy exertion or a high carbohydrate meal, followed by a prolonged rest.⁵ 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.⁷ Deep tendon reflexes are depressed in most patients.⁵ Respiratory muscles are usually, but not always spared.³

Recovery can be spontaneous after 3 to 36 hours, but must be speeded up by K⁺ administration. The onset of paralytic attacks in familial periodic paralysis is often during adolescence, but in most published reports, TPP were found to be between the ages of 20 and 40 years.⁴ The male:female ratio in TPP has been estimated to be 20:1.² Recently, a case of TPP with hypokalaemia has been described in a white woman.⁸ Table 1 shows the differential diagnostic criteria for the two most common forms of hypokalaemic periodic paralysis.

Ober reported seven cases of TPP and provided an excellent review of the literature.¹ It has been postulated that the thyroid hormone directly stimulates Na-K-ATPase dependent K⁺ channel and increases the catecholamine mediated intracellular potassium shift, which is also stimulated by insulin.⁵ Therefore, β blockers are a very useful treatment in TPP, associated with hypokalaemia.⁵

Male dominance and the racial difference in TPP with hypokalaemia are very puzzling.⁸ Difference in HLA subtypes in different racial groups have been reported in the past. Japanese (DRw 8), Singapore Chinese (A2BW22, AW19B17), and Hong Kong Chinese (B5, BW46), all have different HLA subtypes.⁵ HLA DRw8 makes the Japanese susceptible to TPP, and yet the same HLA subtype in the white population makes them susceptible to Graves’ disease.¹⁰ A genetic mutation in the control of Na-K-ATPase activity within the same HLA subtype may explain the racial difference. Interestingly, a genetic mutation in TPP has recently been described in the K⁺-ionic channel gene KCNE3.¹¹ Anti-TPO autoantibody is present in 85%–95% of Graves’ disease cases,¹² which is diagnostic of the condition.

This case shows that among the Chinese and other Oriental population living in Britain, hypokalaemic periodic paralysis may be caused by thyrotoxicosis and that thyroid function studies are mandatory in these people.