Thyrotoxic Periodic Paralysis

An acquired, sporadic disorder characterized by intermittent episodes of muscle weakness alternating with periods of normal muscular function. Occurring during hyperthyroidism and thyrotoxicosis. During attack, hypokalemia is present. May be precipitated by a low plasma concentration of insulin.

Hashitoxic Periodic Paralysis

Most common in Chinese and Japanese. The incidence is estimated at 1.9 to 8.8% of hyperthyroid patients. The disorder is rare in non-Asian populations and only 5% of cases occur in women. A few cases have been reported in African Americans, and this disorder may be more frequent in black patients.

Exact pathophysiology remains to be defined. The following factors appear to be important in the pathogenesis: (a) hyperthyroidism increases Na/K pump ATPase activity, (b) increased platelet Na/K pump ATPase activity has been demonstrated in patients with thyrotoxic periodic paralysis, as compared with thyrotoxic patients, (c) thyroxine sensitizes beta-adrenergic receptors to the effects of catecholamines (Na/K pump ATPase activity is increased), (d) insulin increases Na/K ATPase activity, which may explain the relationship of acute episodes of paralysis to carbohydrate ingestion. These factors result in an intracellular shift of potassium and reduction of the extracellular potassium, causing membrane hyperpolarization. Some of the changes are present in patients who do not develop thyrotoxic periodic paralysis, therefore a role for Na/K ATPase-independent potassium influx has been suggested and the role of Ca2+ gated ion channels is under investigation. The sarcolemmal membrane is thought to be the site of the primary defect. Hypophosphatemia is occasionally found in conjunction with thyrotoxic periodic paralysis and may be synergistic in producing paralysis.

Demonstration of clinical or subclinical hyperthyroidism associated with muscle weakness or paralysis.

Thyrotoxic Periodic Paralysis is uncommon in childhood, with approximately 80% of cases presenting after the age of 20 years. Symptoms include myalgia, fatigue, muscle weakness, and symptoms of hyperthyroidism, although these are often subtle. There may be a history of weakness related to exercise and carbohydrate or alcohol intake. Proximal muscles are more affected than distal muscles, and lower limbs more than upper limbs. Examination commonly reveals a goiter and flaccid paralysis in the affected muscles. Respiratory and bulbar muscles are rarely involved. Cardiac dysrhythmias (atrial fibrillation/ flutter, supraventricular tachycardia ventricular extrasystoles) are common. Electrocardiographic changes reflect the hypokalemia (U waves, small T wave, ST depression, long QT interval). Definitive treatment is correction of the hyperthyroidism. Beta2-antagonism with propranolol may prevent paralysis in the face of hypokalemia. Potassium supplementation may be used in the setting of acute paralysis; however, it should be noted that body potassium stores are normal and that hyperkalemia may occur as paralysis resolves.

Elective surgery is absolutely contraindicated until the patient is rendered euthyroid; paralysis will not occur in the euthyroid state. Examine for evidence of muscle weakness and decrease reflexes. An ECG is mandatory to exclude dysrhythmia and ECG signs of hypokalemia. Laboratory investigations, measure and correct serum electrolytes (Na+, K+, Ca2+, Mg2+), consider measurement of serum phosphate during acute episode. Consider K+ supplementation and propranolol prior to urgent surgery. Delay of urgent surgery by 4 to 6 hours allows resolution of most episodes of paralysis.

Consider premedication and measures to attenuate the stress response to laryngoscopy to minimize catecholamine surges. Neuromuscular monitoring should be used if paralysis is required for surgery. There are no contraindications to regional anesthesia. Avoid large volumes of dextrose-containing fluids.

Use sympathomimetic agents with caution. Drugs contraindicated include potassium-wasting diuretics, cholinesterase inhibitors, and desflurane (relative).

Periodic Paralysis (PP): An inherited condition not associated with high thyroid hormone levels. Characterized by episodes of flaccid muscle weakness occurring at irregular intervals. Most conditions are hereditary and episodic rather than periodic. There are three conditions defined as hypokaliemic, hyperkaliemic and paramyotonic.

Andersen Cardiodysrhythmic Periodic Paralysis Syndrome: This disorder is characterized by the clinical triad of potassium-sensitive periodic paralysis (either low, normal, or high potassium levels), ventricular arrhythmias (bigeminy, long QT interval, ectopy, and bidirectional ventricular tachycardia), and dysmorphic facial features. Sudden death has been reported. Andersen Syndrome must not be confused with Andersen Disease (Glycogen Storage Disease Type IV).