Thyrotoxic myopathy

Definition

Thyrotoxic myopathy is a neuromuscular disorder that occurs due to overproduction of thyroid hormone and is characterized by excessive fatigability, muscle wasting and weakness. It mainly affects muscles of the shoulder, hips and hands. The adverse effects of thyroid hormone on the structure and function of muscles gives rise to this myopathy. Although diagnosis can be tricky, this disorder is reversible with appropriate treatment.

Description

Thyrotoxic myopathy is known by several other names like hyperthyroid myopathy, Graves and Basedow's myopathy or Basedow paraplegia. It was first recognized in the early nineteenth century by Graves and Von Basedow as occurring infrequently in severe hyperthyroidism. In the middle of the twentieth century, researchers found that up to 80% of hyperthyroid patients manifested at least some degree of muscle weakness and this was confirmed on electromyographic studies.

Myopathy or muscle disease is categorized based on the underlying cause, inheritance pattern, etc. One of the broader categories is endocrine myopathies, which occur when there is an abnormal level of endocrine hormones in the body. The thyroid gland produces the hormone thyroxine which regulates maturation of the nervous system, growth and metabolism. Of all the endocrine myopathies, the myopathy due to dysfunction of the thyroid gland is the most common.

Demographics

Although some degree of muscle weakness is common in most hyperthyroid patients, it is still a rare disorder overall and there are no accurate estimates of incidence. In a series of hyperthyroid patients studied by Ruurd Duyff in 2000, 67% had symptoms attributable to myopathy. From a series of over 100 hyperthyroid patients studied by Ramsay in 1974 and Puvanendran et al in 1979, it was found that only 33–64% percent of patients complained of weakness but 61–82% actually had demonstrable weakness on examination. Although hyperthyroidism is more common among women, symptomatic myopathy is more common among middle aged hyperthyroid men. Unlike the classic myopathy, periodic paralysis , which is an unusual neuromuscular complication of hyperthyroidism, is seen among young Asian males.

Causes and symptoms

Much research has been done to elucidate how thyroxine affects muscle function. Muscle is made up of thousands of individual muscle fibers and myofibrils. The latter have myofilaments that are composed of contractile proteins called actin and myosin. In order for a muscle to contract, a command originates from the brain, travels along the spinal cord and then the nerve to terminate on the muscle. This impulse is then transmitted via a complicated process to the myofilaments that contract and relax appropriately. Adenosine triphosphate (ATP) is a chemical that supplies the necessary energy for contraction. Calcium which is released during contraction is taken up to cause muscle relaxation. Muscle fibers are of two types, slow and fast twitch. The slow or type 1 fibers are needed for sustained effort like standing and are more responsive to thyroxine. The fast type 2 fibers are needed for short rapid bursts like sprinting.

In hyperthyroidism, there is an accelerated production of ATP and reuptake of calcium. This leads to very rapid contraction and relaxation. When this occurs repetitively, the structure and mechanics of the slow fiber is changed to that of a fast fiber. Hyperthyroidism increases the body's basal metabolic rate and much of this energy is inefficiently used for muscle contraction. In turn, the muscles lose their endurance, fatigue easily, and become weak and wasted.

Hyperthyroidism can occur due to several causes. Of these, only two are commonly associated with myopathy. One of them is multinodular goiter, when the thyroid gland becomes studded with nodules, enlarges and overproduces thyroxine. The other is Graves disease, where the body launches an autoimmune attack on the thyroid gland and causes it to produce excess thyroxine.

A hyperthyroid person who has muscle weakness may or may not have other recognizable manifestations of hyperthyroidism. Myopathy can sometimes be the first presentation of the underlying hyperthyroid state. There are several types depending on the rapidity of symptom development and patterns of muscle involvement.

CHRONIC THYROTOXIC MYOPATHY The symptom onset is very insidious, so much so that patients very often do not notice the wasting or weakness. An average of six months elapses before the diagnosis is made, as the symptoms are subtle and the progress is very gradual. As mentioned earlier, only around 30% of patients complain of neuromuscular symptoms whereas around 80% show muscle weakness on testing. Patients complain of low exercise tolerance, easy fatigability, difficulty in doing certain tasks, muscle stiffness, muscle twitching and sometimes muscle wasting. Shoulder, hand and then pelvic muscles are affected and tasks like climbing stairs, getting up from a low chair or lifting arms above the shoulders become strenuous. Due to the weakness, movements become clumsy and effortful. The degree of wasting varies among individuals. It is usually mild to moderate but on occasions can be so severe that the scapulae look "winged." Despite a remarkable degree of wasting and weakness, patients remain ambulatory. If the myopathy progresses untreated, then facial muscles, swallowing, and respiratory muscles are involved with resultant difficulty swallowing and breathing. Muscles that control eye movement can also be affected, leading to double vision and squint.

ACUTE THYROTOXIC MYOPATHY This was first described by Laurent in 1944 and is a much rarer form than the chronic myopathy. It is rapidly progressive with profound muscle weakness developing over a few days. Muscle pain , cramps and muscle breakdown develop and lead to rhabdomyolysis. Patients are confused, have very weak respiratory muscles, and develop severe respiratory failure necessitating artificial ventilation.

OCULAR MYOPATHY This is also called "dysthyroid opthalmopathy" or "exopthalmic opthalmoplegia." It is more common in females, can be unilateral and may or may not be associated with chronic thyrotoxic myopathy. It can occur even after treatment for hyperthyroidism. The eye muscles become swollen and weak due to inflammation from an autoimmune attack. Eyes are bulging, the cornea is inflamed and eye movements are restricted especially in the horizontal direction. In severe cases, the cornea is ulcerated and blindness occurs. It progresses over six to 18 months and longer delays in treatment result in severe residual deficit.

THYROTOXIC PERIODIC PARALYSIS This is very rare and occurs mostly in young adult males of Asian ancestry around the third decade. It is characterized by sudden episodes of muscle weakness involving the trunk and limb muscles, developing over few minutes to hours and lasting for hours to a couple of days. It is due to altered muscle membrane excitability secondary to low potassium levels. Although it is reversible spontaneously or with administration of potassium, death can occur due to cardiac arrhythmias.

Diagnosis

The diagnosis is clinical and is usually made by a neurologist who has expertise in neuromuscular disorders. There should be a high index of clinical suspicion as the pattern of muscle weakness is nonspecific and often patients do not know that they are hyperthyroid. The combination of symptoms in a severe case of hyperthyroid myopathy, like muscle wasting, difficulty swallowing and muscle twitching can lead to a mistaken diagnosis of Lou-Gehrig's disease (ALS). A classic picture is that of a patient, who despite a ravenous appetite has significant muscle wasting, weakness and brisk tendon reflexes. Associated hyperthyroid features like enlarged thyroid gland, tremor, bulging eyes, and a fast heart rate may be seen.

Blood tests show an elevated thyroxine level. In Graves disease, antibodies against the thyroid gland are present. Levels of creatine phosphokinase (CPK), a muscle enzyme is normal except when there is acute muscle breakdown. Electromyography is a technique used to diagnose myopathies, by studying the response of muscle contraction to an electrical stimulus. In hyperthyroid myopathy, this may be normal or show a "polyphasic" or "myopathic" response. Muscle biopsy again may be normal or show some degenerating fibers in a non-specific pattern. CT scans or MRI scans can be used to see the swollen eye muscles.

Treatment team

Treatment for hyperthyroid myopathy involves the interaction between a neuromuscular specialist, endocrinologist, a surgeon, and an ophthalmologist. Physiatrists and physical and occupational therapists are also part of the team helping in rehabilitation.

Treatment

Hyperthyroid myopathy is fortunately reversible provided the underlying hyperthyroidism is corrected and a normal thyroid state (euthyroidism) is restored. This can be done with medications, radiation , or surgery. Treatment is also aimed at symptomatic relief, prevention, and treatment of complications.

Medications

Beta-blockers are used to block the effects of adrenaline on peripheral tissues, as adrenergic systems are unregulated in hyperthyroidism. This affords symptomatic but temporary relief. Definitive treatment however aims at reducing the output of thyroxine from the thyroid gland. Propylthiouracil and methimazole are medications that inhibit production and release of thyroxine and also block tissue effects of thyroxine. Radiation in the form of oral radio-iodine therapy destroys the overactive thyroid gland. Steroids, other anti-inflammatory medications, or radiation is used to treat the ocular myopathy. Artificial tears and lubricating ointments are used to prevent corneal ulceration. Potassium chloride given intravenously will reverse the thyrotoxic periodic paralysis.

Surgical treatment

Surgical removal of portions of the enlarged and unsightly thyroid gland can be done to restore euthyroid state. In severe cases of ocular myopathy, surgical widening of the walls of the orbit is done to allow the eyes to decompress. Corneal grafting can be done to treat corneal ulceration.

Recovery and rehabilitation

When proper treatment is given, full recovery of the myopathy is possible and complications can be avoided. Physical therapists can help in devising muscle strengthening exercises and in preventing muscle contractures. Protective eye glasses and eye patches are used to prevent corneal exposure and ulceration.

Clinical trials

There were no clinical trials ongoing as of early 2004, mainly because there is an effective treatment already available.

Prognosis

Prognosis is quite good. In two to four months after euthryoid state is achieved, muscle weakness improves. But it may take up to a year for muscle bulk to return. Respiratory failure is very rare. Patients have a normal life expectancy and lead normal lives if properly and promptly treated.

Resources

BOOKS

Aminoff, Michael J., editor. "Thyroid disorders and the nervous system." Neurology and General Medicine. Philadelphia: Churchill Livingstone, 2001.

Victor, Maurice, and Allan H. Ropper, eds. "Electrophysiologic Testing and Laboratory aids in the diagnosis of neuromuscular disease." Principles of Neurology. New York: McGraw-Hill, 2001.

Victor, Maurice, and Allan H. Ropper, eds. "Principles of Clinical Myology: Diagnosis and Classification of Muscle Diseases-General Considerations." Principles of Neurology. New York: McGraw-Hill, 2001.

Victor, Maurice, and Allan H. Ropper, eds. "The Metabolic and Toxic Myopathies." Principles of Neurology. New York: McGraw-Hill, 2001.

PERIODICALS

Alshekhlee, A., H. J. Kaminski, and R. L. Ruff. "Neuromuscular manifestations of endocrine disorders." Neurologic Clinics 20 (February 2002): 35–58.

Horak, H., and R. Pourmand. "Endocrine myopathies." Neurologic Clinics 18 (February 2000): 203–213.

Klein, I., and K. Ojamaa. "Thyroid (neuro) myopathy." The Lancet 356 (August 2000): 614.

WEBSITES

National Institutes of Neurological Disorders and Stroke (NINDS). Thyrotoxic Myopathy Information Page. <http://www.ninds.nih.gov/health_and_medical/disorders/thyrotoxic_myopathy.htm.>.

ORGANIZATIONS

Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718-3208. (520) 529-2000 or (800) 572-1717; Fax: (520) 529-5300. [email protected]. <http://www.mdusa.org>.

National Institute of Health Neurological Institute. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424. <http://www.ninds.nih.gov/>.

Chitra Venkatasubramanian, MBBS, MD