Thyrotoxic Periodic Paralysis

Thyrotoxic periodic paralysis is episodic flaccid weakness from intracellular potassium shifts during thyrotoxicosis, with hypokalaemia. It is most common in men of Asian and Hispanic ancestry aged 20 to 40 years, affecting up to 2% of thyrotoxic Asian patients, and 0.1% in other groups.

Pathophysiology. Excess thyroid hormone increases sodium potassium ATPase activity. Triggers such as high carbohydrate meals, rest after exercise, and stress raise insulin and adrenaline, which move potassium into cells. Variants in KCNJ18 are linked.

Sudden attacks of proximal leg more than arm weakness, lasting hours to a few days, often at night or after exercise or a meal. Reflexes are reduced. Respiratory and bulbar muscles are usually spared, but arrhythmia can occur. Signs of hyperthyroidism (weight loss, palpitation, tremor, goitre) may be mild.

Red flags.

• Potassium under 2.5 mmol/L, or ECG changes.
• Respiratory weakness or arrhythmia.

During an attack: low potassium (usually 1.5 to 3.0 mmol/L), low phosphate and magnesium, raised creatine kinase, suppressed thyroid stimulating hormone and raised free thyroxine and triiodothyronine. ECG shows sinus tachycardia, U waves and arrhythmia. Check the cause of thyrotoxicosis (thyroid antibodies, uptake scan). Urine potassium is low.

Differential diagnosis.

• Familial hypokalaemic periodic paralysis, Andersen-Tawil syndrome.
• Renal tubular acidosis, Gitelman syndrome and primary hyperaldosteronism.
• Gastrointestinal potassium loss, Guillain-Barre syndrome and myasthenia.

Acute attack.

• Oral potassium chloride 20 to 40 mmol, repeated every 1 to 2 hours up to 100 mmol in 24 hours, with ECG monitoring. Use IV potassium chloride only when oral treatment is not possible: 10 mmol/hour (maximum 20 mmol/hour), in saline without dextrose, which worsens hypokalaemia. Check potassium every 1 to 2 hours, since rebound hyperkalaemia occurs in up to 40%.
• Propranolol 3 mg/kg orally (up to 160 mg) as a single dose rapidly reverses the attack and prevents rebound hyperkalaemia.

Prevention. Control thyrotoxicosis with antithyroid drugs (carbimazole 15 to 40 mg daily, then titrate), beta blockers (propranolol 40 mg three times daily) until euthyroid, and definitive treatment (radioiodine or thyroidectomy). Attacks stop when euthyroid.

Lifestyle. Avoid large carbohydrate meals, alcohol and strenuous exercise.

Monitoring. Potassium, ECG, and thyroid function every 4 to 6 weeks.

Referral and escalation. Refer to endocrinology. Admit for monitoring in severe attacks.

Special groups. In pregnancy, propylthiouracil is used in the first trimester, with specialist advice.