Thyrotoxic myopathy (TM) is a neuromuscular disorder that develops due to the overproduction of the thyroid hormone thyroxine. Also known as hyperthyroid myopathy, TM is one of many myopathies that lead to muscle weakness and muscle tissue breakdown. Evidence indicates the onset may be caused by hyperthyroidism. There are two known causes of hyperthyroidism that lead to development thyrotoxic myopathy including a multinodular goiter and Graves' disease. Physical symptoms of TM may include muscle weakness, the breakdown of muscle tissue, fatigue, and heat intolerance. Physical acts such as lifting objects and climbing stairs may become increasingly difficult. If untreated, TM can be an extremely debilitating disorder that can, in extreme rare cases, lead to death. If diagnosed and treated properly the effects can be controlled and in most cases reversed leaving no lasting effects.
Symptoms and signs
Physical symptoms may include: Muscle weakness Degeneration of muscle tissue Fatigue Heat intolerance
Chronic TM
Symptoms of chronic TM arise slowly. Patients usually cite decreased exercise tolerance, increased fatigue, and difficulty completing certain tasks after six months of onset. If chronic TM goes untreated worse symptoms may develop including difficulty swallowing and respiratory distress. These occurrences are rare since diagnosis of chronic TM usually occurs during the early stages of onset, before these symptoms develop.
Acute TM
Acute TM is rarer than chronic TM and symptoms appear within days of onset. Acute TM degrades muscle fibers rapidly. Due to the rapid degradation of muscle fibers patients usually cite severe muscle cramps and muscle pain. Some acute TM patients may present symptoms of blurred vision and bulging eyes due to eye muscle degradation and inflammation, but documented cases are rare. Acute TM patients usually have very weak respiratory muscles and often severe respiratory failure occurs.
Cause
TM is directly related to thyroxine toxicity. It is believed this disorder is a direct result of hyperthyroidism, specifically hyperthyroidism caused by Graves' disease or a multinodular goiter. Both cause the thyroid gland to overproduce thyroxine. A multinodular goiter is a condition where the thyroid develops nodules. Overproduction of thyroxine is due to the enlargement of the thyroid gland. Graves' disease is an autoimmune condition where the immune system chronically stimulates the TSH receptor in the thyroid and induces overproduction of the thyroxine hormone.
Pathophysiology
Excess thyroxine is believed to bring about the onset of thyrotoxic myopathy and eventually cause the degradation of muscle tissue. Thyroxine is a hormone produced in the thyroid gland that regulates the growth metabolism of the nervous system and regulates basal metabolic rate of many cell types. Scientists agree thyroxine brings about the degradation of muscle fibers specifically at the motor end plates of neuromuscular junctions. There is debate as to whether thyroxine degrades the motor end plates from the muscular side, from the nervous system side, or a combination.
To understand how high levels of thyroxine can be toxic and lead to thyrotoxic myopathy physiologically, consider basic neuromuscular junction function. Under normal circumstances, muscle contraction occurs when electrical impulses travel down descending axons from the brain or spinal cord towards the neuromuscular junction. The axon terminal depolarizes and releases Acetylcholine (ACh), a neurotransmitter, which in turn stimulates the motor end plate (MEP) of the muscle fiber the nerve is innervating. When the MEP depolarizes the muscle fiber releases calcium initiating the process of muscle contraction.
With the onset of TM due to thyroxine toxicity, there is evidence to suggest that structural changes in MEPs could lead to muscle fiber degradation, weakness, and fatigue. Research indicates that decreased levels of Acetylcholinesterase AChE, an enzyme that breaks down ACh, was observed within the neuromuscular junction. This decrease in AChE blocks degradation of ACh causing ACh to increasingly stimulate the MEP of the muscle fiber. Over stimulation of MEP could cause more muscle contractions which eventually evoke muscle fiber fatigue, weakness, and finally degradation, which are characteristic symptoms of TM. It is believed this decrease in AChE and MEP structural changes could be the result of over stimulation of thyroxin blocking the axoplasmic flow of trophic factors down the axon terminal especially considering thyroxine's role in nervous system growth and metabolism regulation.