Thyrotoxic myopathy
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| Thyrotoxic myopathy | |
| Classification and external resources | |
| ICD-9 | 359.5 |
|---|---|
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 of TM may be caused by hyperthyroidism (Kazakov, 1992). There are currently two known causes of hyperthyroidism that lead to development of TM including a multinodular goiter and Graves disease. Physical symptoms of TM may include muscle weakness, the breakdown of muscle tissue, fatigue, and heat intolerance (Quin, 1951).� Physical acts such as lifting objects and climbing stairs may become increasingly difficult (Horak, 2000). 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 of TM can be controlled and in most cases reversed leaving no lasting effects.
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[edit]Symptoms
Physical Symptoms may include:
- Muscle Weakness
- Degeneration of Muscle Tissue
- Fatigue
- Heat Intolerance
Chronic TM - Symptoms of chronic TM arise slowly overtime. Patients usually complain of decreased exercise tolerance, increased fatigue, and difficulty completing certain tasks after six months of TM onset (Kazakov, 1991; Quinn, 1951). 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 prior to these symptoms development.
Acute TM - Acute TM is more rare than chronic TM and unlike chronic TM symptoms appear within days of TM onset. Acute TM degrades muscle fibers rapidly. Due to the rapid degradation of muscle fibers patients usually complain of severe muscle cramps and muscle pain. Some acute TM patients may also 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 ( Lichtstein, 2006).
[edit]Etiology
TM is a disorder that 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 diseases 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 attacks the thyroid and induces overproduction of the thyroxine hormone.
[edit]Pathophysiology
Excess thyroxine is believed to bring about the onset of TM 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 bring 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 of both (Kazakov, 1992).
To understand how high levels of thyroxine can be toxic and lead to TM physiologically first 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 releasesAcetylcholine (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 muscle fiber degradation, muscle fiber weakness, and muscle fiber fatigue. Research indicates that decreased levels of Acetylcholinesterase AChE, an enzyme that breaks down ACh, was observed within the neuromuscular junction (Kazakov, 1992). 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 (Kazakov, 1992). 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 (Kazakov, 1986) especially considering thyroxine's role in nervous system growth and metabolism regulation. On the other hand other research indicates muscle fiber fatigue, weakness, and degradation associated with TM is the direct action thyroxine has on the muscle fibers themselves. Research suggests thyroxine directly causes a decrease in protein kinase affinity to cAMP within muscle fibers (Kazakov, 1992; Kazakov, 1995). This causes an increase in cAMP within the muscle fibers since protein kinases are not inactivating cAMP. Increased levels of cAMP within the muscle fibers cause increased release of Ca2+ from the muscle fiber's sarcoplasmic reticulum which eventually leads to more muscle contractions. Like the nervous system proposal increased muscle contractions eventually evoke muscle fiber fatigue, weakness, and finally degradation, which are characteristic symptoms of TM. Considering there is evidence to support both theories it has been suggested that toxic levels of thyroxine may ultimately attack muscle fibers both directly and indirectly via the motor neurons that innervate the affected muscle fibers.
[edit]Diagnosis
TM is usually diagnosed by a neurologist who has extensive experience diagnosing neuromuscular disorders. There are many types of neuromuscular disorders that all present similar physical symptoms. Extensive clinical tests are performed first to determine if there is a neuromuscular disorder and then to determine which disorder it is. Electromyography is used to diagnose myopathies by comparing muscle contraction responses to electrical stimulus (Chiu, 2006). For TM results may indicate normal responses or myopathic responses depending on how the disorder has progressed. Early detection may indicate normal contractual responses while highly progressed TM may show a significant decrease in contraction response. Blood tests are then conducted to determine the specific myopathy. For TM, blood tests reveal increased thyroxine levels. Increased thyroxine levels accompanied with decreased neuromuscular responses together provide best evidence for TM diagnosis. Creatine phosphokinase levels are also examined during the blood tests. Normal or increased levels may be observed with TM depending on the severity of TM's progression. Normal levels indicate possible early stages of progression while increased levels may indicate later stages of TM progression. Muscle biopsies may also be taken and examined to determine TM's progression with respect to physical degradation. Like measured creatine phosphokinase levels results from the muscle biopsy characteristic of TM typically show normal to severe fiber degradation with respective indications to the severity of TM progression.
[edit]Treatment
Treatment for TM is typically done with the possible collaboration of many different specialists within the medical field. Usually a neuromuscular specialist, an endocrinologist, a surgeon, and an ophthalmologist will combine their efforts to successfully treat patients diagnosed with TM. In the event a patient develops significant to severe muscle degradation as a result of TM a physical therapist may be consulted for rehabilitation. Since excess thyroxine leads to onset of TM, the overall goal of treatment is to reduce to overproduction of thyroxine from the thyroid gland and restore normal thyroid homeostasis. This can be accomplished three ways including using medication, radiation, and surgery. First choice involves using a series of medications to not only alleviate the symptoms caused by TM but also reverse the damage by blocking the production of thyroxine from the thyroid gland. Beta-blockers are used to alleviate the symptoms associated with TM. While beta-blockers alleviate symptoms they do not reduce the damage done by excess thyroxine. Medications such as propylthiouracil and methimazole are also administered to not only block the release of thyroxine from the thyroid but to block the damage thyroxine inflicts on muscle fiber tissue. Another treatment option available to patients is the use of radio active iodine which directly destroys the overactive thyroid gland. The thyroid gland naturally uses iodine to produce thyroxine and other hormones and yet cannot distinguish between normal iodine and the radioactive version. Administering the radioactive isotope causes the thyroid to take in the lethal iodine and quickly radiation destroys the thyroid (Horak, 2000). Typically overproduction of thyroxine using radio-iodine is blocked with one dose. The drawback to this treatment is the thyroid gland is completely destroyed and patients often develop hypothyroidism. Some patients develop hypothyroidism only a few months after treatment while others may not be affected for 20-30 years. Upon the onset of hypothyroidism patients must begin a life long regimen of thyroid replacement hormones. While the onset of hypothyroidism is most common with radio-iodine treatment the condition has been observed in patients treated with medication series and surgery. The last option for TM treatment includes surgical removal of portions of the thyroid which can also be performed to restore thyroid homeostasis. This treatment option usually is done when overproduction of TM is caused by multinodular goiters. Since these goiters enlarge the thyroid and can cause the patient to become physically disfigured surgical treatment can alleviate both the aesthetic and physiological affects simultaneously.
[edit]Epidemiology
The onset of TM requires toxic levels of the thyroxine hormone due to overproduction by the thyroid gland. Documented cases have only been diagnosed in conjunction with patients also suffering from hyperthyroidism. While hyperthyroidism is more common in women the development of TM was more common among men with hyperthyroidism. Case studies of patients with diagnosed hyperthyroidism showed that only about half of them complained of symptoms characteristic of TM (Duyff, 2000). Further examination as described above indicated that about 75% of the studied patients showed signs of muscle fiber degeneration (Duyff, 2000). This indicates that either at the time of study some patients were in early stages of TM or the symptoms were so insignificant patients.
[edit]Prognosis
TM is a disorder that, with proper diagnosis and effective treatment, can be beaten. Patients who are diagnosed with TM have a normal life expectancy and can ultimately lead healthy lives if proper treatment is administered. Typically, once the over production of thyroxine is corrected and thyroid function adequately reaches a level of homeostasis patients begin to regain muscle strength within two to four months. Depending on the severity of the TM progression symptoms may take up to a year to completely reverse the damage done by TM. Untreated TM can eventually cause severe respiratory distress or even arrest possible leading to death yet this is very rarely seen.
[edit]References
- Chiu WY, Yang CC, Huang IC, Huang TS (Dysphagia as a manifestation of thyrotoxicosis: Report of three cases and literature review. Dysphagia 19:120-124.2004).
- Duyff, R., Bosch, J., Laman, D., Neuromuscular findings in Thyroid Dysfunction: a prospective clinical and electrodioagnostic study. Neural Neurosurg Psychiatry. 68:750-755. 2000
- Horak HA, Pourmand R (Endocrine myopathies. Neurologic Clinics 18:203-+.2000).
- Kazakov, V.M., Terminal Intramuscular Motor Innervation and Motor End-Plates in Thyrotoxic Myopathy.2:343-349(1992)
- Kazakov V (Pathogenesis of thyrotoxic myopathy (TM): On the hypothesis of muscle weakness origin, once again. Brain Pathology 10:544-545.2000).
- Kazakov VM (DIFFERENTIAL-DIAGNOSIS OF THYROTOXIC MYOPATHY. Klinicheskaya Meditsina 69:107-111.1991).
- Kazakov VM, Katinas GS, Skorometz AA (PATHOGENESIS OF EXPERIMENTAL THYROTOXIC MYOPATHY. European Neurology 25:212-224.1986).
- Kazakov VM, Kovalenko TM (EXPERIMENTAL THYROTOXIC MYOPATHY - AUTORADIOGRAPHY OF PROTEIN-SYNTHESIS IN SKELETAL-MUSCLE AND MOTOR-NEURONS OF SPINAL-CORD. Neuromuscular Disorders 5:47-52.1995).
- Lichtstein DM, Arteaga RB (Rhabdomyolysis associated with hyperthyroidism. American Journal of the Medical Sciences 332:103-105.2006).
- Mano T, Iwase K, Yoshimochi I, Sawai Y, Oda N, Nishida Y, Mokuno T, Kotake M, Nakai A, Hayakawa N, Kato R, Nagasaka A, Hidaka H. CHANGES IN CALMODULIN CONCENTRATION AND CYCLIC 3',5'-NUCLEOTIDE PHOSPHODIESTERASE ACTIVITY IN SKELETAL-MUSCLE OF HYPERTHYROID AND HYPOTHYROID RATS. Journal of Endocrinology 146:287-292.1995.
- Quinn EL, Worcester RL (CHRONIC THYROTOXIC MYOPATHY - REPORT OF A CASE. Journal of Clinical Endocrinology 11:1564-1571.1951).
- Riis ALD, Jorgensen JOL, Gjedde S, Norrelund H, Jurik AG, Nair KS, Ivarsen P, Weeke J, Moller N. Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown. American Journal of Physiology-Endocrinology and Metabolism 288:E1067-E1073.2005.
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