Thyrotoxic periodic paralysis.

The interesting case report by Laroia et al (1) illustrates a rare endocrine emergency associated with thyrotoxicosis. Hypokalemic periodic paralysis has been linked to thyrotoxicosis of varying etiologies. These etiologies include Graves' disease, toxic adenoma, toxic multinodular goiter, factitious thyrotoxicosis, thyrotropin-producing pituitary tumors, and lymphocytic thyroiditis. (2) Any cause of thyrotoxicosis, including overzealous thyroxine replacement, can provoke an attack of thyrotoxic periodic paralysis in susceptible patients.

We can now add amiodarone to this list, as reported by Laroia et al. (1) The link between amiodarone and thyrotoxic periodic paralysis presumably relates to the iodine content of this medication. Daily ingestion of 400 mg of amiodarone yields approximately 150 mg iodine. Ober and Hennessy (3) described thyro-toxic periodic paralysis with iodine-induced thyrotoxicosis approximately 20 years ago. The report by Laroia et al (1) is timely, since amiodarone use is proliferating. Its use has expanded to include a role in advanced cardiac life-support protocols, and clinicians should therefore be aware of its link to thyrotoxicosis and associated presentations, including hypokalemic periodic paralysis.

The association between thyrotoxicosis and periodic paralysis was described in the German literature at the turn of the century. (4) Dunlap and Kepler (5) documented the association between exophthalmic goiter and periodic paralysis in the United States. McFadzean and Yeung (6) reported periodic paralysis with thyrotoxicosis in a Chinese patient. The possible racial predilection of thyrotoxic periodic paralysis has received considerable attention, and the prevalence of periodic paralysis is estimated to be between 1% and 5% of Chinese and Japanese patients with thyrotoxicosis. (6) The prevalence of this disorder has decreased in recent times in Japan, presumably related to the increased intake of potassium and reduced ingestion of carbohydrate. As indicated in the report by Laroia et al, (1) hypokalemic periodic paralysis can occur in Caucasians. Indeed, its prevalence may be underestimated in Caucasians and African Americans. (2)

Male sex predominance is a characteristic of thyrotoxic periodic paralysis, and the condition usually presents in the third to fifth decade of life. Thyrotoxic periodic paralysis has no familial tendency, unlike familial hypokalemic periodic paralysis. Acute muscle weakness may be focal or generalized, and may be variable in severity. Proximal muscles, especially in the lower limbs and recently exercised muscles, appear most likely to be affected. Classically, the attacks start while in bed at night or early in the morning following a day of strenuous exercise. (2) Early symptoms may include an aching, stiffness, or cramp, which can alert the patient to an impending attack. Patients alerted by these premonitory symptoms may sometimes abort an impending attack by increasing physical activity. Muscles recover in reverse order of their involvement, and may remain tender during the recovery period.

Since myasthenia gravis may occur concurrently with Graves' disease and its manifestations may be exacerbated during thyrotoxicosis, it is important to note the distribution of muscle weakness. Thyrotoxic periodic paralysis usually does not affect cranial nerve, bulbar, or respiratory muscle function. No sensory or mental symptoms are usually found. In general, reflexes are decreased, but, as in the patient described by Laroia et al, (1) increased tendon reflexes have also been reported. Body stores of potassium are at normal levels; the hypokalemia results from an intracellular shift. Rarely, such a shift in potassium can be associated with symptoms in the absence of frank hypokalemia. Serious cardiac rhythm disturbances may occur in hypokalemic thyrotoxic periodic paralysis. The degree of weakness appears to be related to the extent of hypokalemia, and resolution can be aided by potassium replacement. Hypokalemia is not the sole etiology for the paralysis, however. Hypophosphatemia may occur, and rhabdomyo lysis has also been observed.

A wide range of events may precipitate an attack, including intake of high amounts of carbohydrate, exercise, infection, trauma, menses, and stress. Attacks also appear more common in the summer months, possibly due to increased sweating and ingestion of drinks high in carbohydrates. It is clear that thyrotoxicosis has to be present to invoke these episodes of paralysis, and in the vast majority of cases hypokalemia is present. The etiology of the thyrotoxicosis appears less critical. Thyrotoxicosis may not be as clinically evident as in the patient reported by Laroia et al. (1) The paralytic episodes may rarely precede the development of thyrotoxicosis, and the paralysis appears unrelated to the duration and degree of thyrotoxicosis. The increased intracellular shift of potassium has been attributed to enhanced activity of [Na.sup.+], [K.sup.+]-ATPase activity. Thyroid hormone therapy, hyperinsulinemia, and androgen supplementation may increase the activity of this enzyme. The activity of the calcium pump m ay also be decreased, affecting oxidative phosphorylation. Partial defects in the calcium and sodium voltage-gated channel may be responsible for these attacks in the presence of thyrotoxicosis.

Definitive treatment of this condition is the correction of the thyrotoxic state, along with potassium replacement. In many instances, the potassium level gradually returns to normal without intervention; however, the potential cardiac effects of hypokalemia are so profound that parenteral treatment is usually advisable. Avoiding usual precipitating factors pending resolution of thyrotoxicosis is advisable. Prophylactic potassium therapy has not been shown to prevent attacks, but treatment with propranolol and spironolactone may be beneficial in reducing the frequency of attacks. Acetazolamide therapy has been useful in familial periodic paralysis, although its efficacy in thyrotoxic periodic paralysis is doubtful and its effects potentially deleterious. (7) In a significant number of cases, amiodarone-induced thyrotoxicosis responds poorly to medical management, and a total thyroidectomy may need to be considered. In these situations, the prevention of hypokalemia will present additional challenges to anest hesia management in patients with thyrotoxic periodic paralysis.

Thyrotoxic hypokalemic periodic paralysis needs to be included in the differential diagnosis of acute muscle weakness. The increased use of amiodarone favors a greater occurrence of thyrotoxic hypokalemic periodic paralysis. It may be prudent to check thyroid function tests in patients with acute onset of muscle weakness and/or hypokalemia.

Alan N. Peiris, MD, PhD

Mountain Home Veterans Affairs Medical Center

Division of Endocrinology

East Tennessee State University 

PO Box 70622

Johnson City, TN 37614-0622

References

(1.) Laroia ST, Zaw KM, Ganti AK, et al: Amiodarone-induced thyrotoxicosis presenting as hypokalemic periodic paralysis. South Med J 2002; 95:1326-1328

(2.) Magsino CH Jr, Ryan AJ Jr: Thyrotoxic periodic paralysis. South Med J 2000; 93:996-1003

(3.) Ober KP, Hennessy JF: Jodbasedow and thyrotoxic periodic paralysis. Arch Intern Med 1981; 141:1225-1227

(4.) Rosenfeld M: Akute aufsteigende Lahmungen bei Morbus basedow. Berl Klin Wochenschr 1902; 39:538

(5.) Dunlap H, Kepler E: A syndrome resembling familial periodic paralysis occurring in the course of exophthalmic goiter. Endocrinology 1931; 15:541-546

(6.) McFadzean AJS, Yeung R: Periodic paralysis complicating thyrotoxicosis in Chinese. BMJ 1967; 1:451-455

(7.) Shulkin D, Olson BR, Levey GS: Thyrotoxic periodic paralysis in a Latin-American taking acetazolamide. Am J Med Sci 1989; 297:337-338