Laboratory Approach in the Evaluation of a Suspected Myopathy
At the conclusion of the history and physical examination, a relatively short list of possible diagnoses should be under consideration. Laboratory studies can then be judiciously used to make a final diagnosis. It is important to recognize that laboratory testing in myopathies may serve different purposes, depending on the type of test and the nature of the problem. Some tests, such as DNA analyses in genetic disorders and enzyme assays in the metabolic myopathies, will provide a specific diagnosis. Other tests, such as electromyography and the ischemic forearm test, suggest the type of problem but not an exact diagnosis.
Creatine kinase (CK) is the single most useful laboratory study for the evaluation of patients with a suspected myopathy. The CK is elevated in the majority of patients with muscle disease but may be normal in slowly progressive myopathies. The degree of CK elevation can also be helpful in distinguishing different forms of muscular dystrophy. For example, in Duchenne dystrophy, the CK is invariably at least 10 times (and often up to 100 times) normal, whereas in most other myopathies there are lesser elevations. The other exceptions are LGMD 1C (caveolinopathy), LGMD 2A (calpainopathy), and LGMD 2B (dysferlinopathy), where CK may also be markedly elevated. The CK level may not be elevated in some myopathies or may even by lowered by several factors including profound muscle wasting, corticosteroid administration, collagen diseases, alcoholism, or hyperthyroidism.
In the inflammatory myopathies, the CK is usually, but not always, elevated, more so in polymyositis and dermatomyositis than inclusion body myositis. It is important, however, to recognize that the degree of CK elevation in these disorders has an imprecise relationship to muscle strength and therefore should not be relied on completely in following a patient's response to therapy. It is also important to remember that an elevation of serum CK does not necessarily imply a primary myopathic disorder ( Table 17 ). Many times the CK will rise modestly (usually to less than 10 times normal) in motor neuron disease and uncommonly, CK elevations may be seen in Guillain Barré syndrome or chronic inflamma-tory demyelinating polyradiculoneuropathy. Endocrine disorders such as hypothyroidism and hypoparathyroidism can also be associated with high CK levels. Causes of CK elevation other than neuromuscular disease include muscle trauma (falls, intramuscular or subcutaneous injections, EMG studies, electric shock), viral illnesses, hypothermia, cardiac injury, seizures, severe dyskinesias, or vigorous exercise. In these cases, CK elevations are usually transient and less than 5x normal.
Medications can cause serum CK elevations either with or without associated muscle weakness ( Table 18 ). Race and gender can also affect serum CK ( Table 19 ). CK levels are frequently above the “normal” range in some African-American individuals and in patients with enlarged muscles. Occasionally, benign elevations of CK appear on a hereditary basis. It is extremely unusual for a slightly elevated CK (threefold or less) to be associated with an underlying myopathy in the absence of objective muscle weakness or pain.
Serum tests for other muscle enzymes are significantly less helpful than the determination of the CK. Enzymes such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), and lactate dehydrogenase (LDH) may be slightly elevated in myopathies. Because AST, ALT, and LDH are often measured in screening chemistry panels, their elevation should prompt CK measurement to determine if the source is muscle or liver. If a patient with an inflamma-tory myopathy is treated with an immunosuppressive agent that may cause hepatoxicity, the liver specific enzyme, gamma glutamic transferase (GGT) should be followed.
In general, CK isoenzymes are not helpful in evaluating myopathies. CK-MM elevations are typical of muscle disease, but CK-MB is also elevated in myopathies and does not indicate that cardiac disease is present. In mitochondrial disorders, serum lactate can be a useful screening test because it is commonly elevated at rest. Blood and urine carnitine and acylcarnitine assays can be helpful in the diagnosis of a disorder of lipid metabolism.
Semin Neurol. 2008;28(2):228-240. © 2008 Thieme Medical Publishers
Cite this: Clinical Approach to Muscle Diseases - Medscape - Apr 01, 2008.