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425 Myopathies associated with endocrine/metabolic disorders and carcinoma Genetic testing – NCV/EMG ++ Laboratory +++ Imaging Biopsy + +++ Fig. 32. Muscle from a patient with diabetes mellitus showing myolysis with degenerating fi-bers (arrow heads) This is variable and depends on the specific systemic disorder, however proxi-mal muscles are most usually affected. This is variable depending on the specific cause of myopathy. Most of these myopathies progress slowly, although rapid progression of symptoms may be observed with thyrotoxicosis. If treated most endocrine related myopathies are self limiting. Myopathies related to paraneoplastic disorders are usually not treatable. Any age although most are observed in adults. Paraneoplastic related myopa-thies are more common in older patients. This disorder may be associated with a painful myopathy that can simulate polymyalgia or polymyositis. In severely hypothyroid children a syndrome characterized by weakness, slow movements, and striking muscle hypertrophy may be observed. Percussion myotonia and myoedema may be observed in patients with hypothyroidism. Distribution/anatomy Time course Onset/age Clinical syndrome Hypothyroidism This is trial version www.adultpdf.com 426 Hyperthyroidism Hypoparathyroidism Hyperparathyroidism Cushing syndrome and corticosteroid atrophy Acromegaly Diabetes Uremia and myopathy Carcinomatous myopathy Pathogenesis Diagnosis Thyrotoxicosis is associated with muscle atrophy and weakness. It may also be associated with a progressive extraocular muscle weakness, ptosis, periodic paralysis, myasthenia gravis, spastic paraparesis and bulbar palsy. Subjects may have brisk reflexes and fasciculations similar to amyotrophic lateral sclerosis. Affected patients may have tetany, muscle spasm, and occasionally weakness. Patients may have proximal weakness, muscle atrophy, hyperreflexia, and fasciculations. Occasionally muscle atrophy and weakness may be observed under conditions of hypercortisolemia. The muscles may appear enlarged, however this disorder is usually associated with mild proximal upper or lower extremity muscle weakness. Diabetes is not associated with a generalized myopathy, however muscle necrosis or inflammation may occur in diabetic amyotrophy. In Flier’s syn-drome, there is muscle pain, cramps, fatigue, acanthosis nigricans and pro-gressing enlargement of the hands and feet, and impaired glucose tolerance. Hypoglycemia may be associated with muscle atrophy as part of a motor neuron type syndrome. It does not produce primary myopathy. In chronic renal failure patients may have proximal weakness and in addition myoglobinuria may occur. This may be seen as part of an inflammatory myopathy, may also be observed in carcinoid syndrome, or may occur due to a metabolic disturbance. Direct invasion of muscle is rare although it may be observed with leukemias and lymphomas. The pathogenesis depends on the specific muscle disorders indicated above. Laboratory: A variety of electrolyte and endocrine changes support the diagnosis as indicat-ed under the specific disease. The CK may be normal or significantly elevated e.g. in diabetic muscle infarction or with hypothyroidism. Electrophysiology: The EMG is dependent on the specific disorder, but in general there is evidence of myopathic changes in affected muscles. Imaging: Muscle imaging may be of value. Muscle biopsy: In both hypo and hyperthyroidism the muscle biopsy is often normal, although there may be evidence of mild fiber atrophy. In hyperparathyroidism and acromegaly there may be mild type 2 fiber atrophy. Evidence of inflammation and muscle infarction may be observed in affected muscle in diabetic amyotro-phy. Muscle destruction following rhabdomyolysis may also be seen in this condition (Fig. 32). Inflammatory changes may be observed in carcinomatous myopathy, or as part of a paraneoplastic syndrome. This is trial version www.adultpdf.com 427 This is wide and includes the different causes of metabolic and systemic disease associated with myopathy. In addition the inflammatory myopathies e.g. PM, DERM, and IBM may resemble these disorders. Lambert-Eaton myasthenic syndrome (LEMS) may mimic a paraneoplastic myopathy. Type 2 fiber atrophy due to any cause may mimic a metabolic myopathy. The therapy of the underlying systemic disease often leads to improvement of the myopathy. This is dependent on the specific disorder, but if appropriate therapy is institut-ed the prognosis is usually good for the endocrine disorders such as hypothy-roidism, hyperthyroidism, hyperparathyroidism, acromegaly, and diabetes. Dyck PJ, Windebank AJ (2002) Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment. Muscle Nerve 25: 477– 491 Horak HA, Pourmand R (2000) Endocrine myopathies. Neurol Clin 18: 203–213 Madariaga MG (2002) Polymyositis-like syndrome in hypothyroidism: review of cases reported over the past twenty-five years. Thyroid 12: 331–336 Differential diagnosis Therapy Prognosis References This is trial version www.adultpdf.com 428 Myotonia congenita Genetic testing ++ NCV/EMG +++ Laboratory – Imaging Biopsy – + Fig. 33. Myotonia congenita. A Muscle myotonia in the hypoth-enar muscles. B Myotonic dis-charges in the EMG from affect-ed muscle Fig. 34. Thomson’s myotonia congenita. A Increased muscle bulk in the arms and chest in a patient with Thomson’s disease. B Hypertrophy of the extensor digitorum brevis muscle This is trial version www.adultpdf.com 429 Variable, may affect both limb and facial muscles. Progresses very slowly over a lifetime. Usually strength is spared. Distribution/anatomy Time course – Myotonia congenita (Thomsen): onset in infancy. Onset/age – Myotonia congenita (Becker): onset is usually in early childhood. Myotonia is usually mild, approximately 50% may have percussion myotonia. The myotonia (Fig. 33) is associated with fluctuations, and may be worsened by cold, hunger, fatigue and emotional upset. Muscle hypertrophy is seen in many patients (Fig. 34), and occasionally patients may complain of myalgias. Patients may report a “warm-up” phenomenon, in which the myotonia decreases after repeated activity. Muscle strength is usually normal. Patients may also have a “warm-up” phenomenon. The disease is more severe than Thomsen’s, and although strength is usually normal in childhood, there is often mild distal weakness in older individuals. Strength often deteriorates after short periods of exercise. Hypertrophy may also be observed in the leg muscles, although it is less common than in Thomsen’s disease. Mild myotonia occurring late in life, with less muscle hypertrophy. Thomsen’s disease is due to a defect of the muscle chloride channel (CLCN1). Thomsen’s disease is an autosomal dominant disorder, with the gene abnormal-ity localized on chromosome 7q35. The mutation interferes with the normal tetramer formation on the chloride channel. Chloride conductance through the channel is eliminated or reduced. Normal chloride conduction is necessary to stabilize the membrane potential. Without chloride conductance there is in-creased cation conductance after depolarization, and spontaneous triggering of action potentials. In missense mutations of the chloride channel there is a partial defect in normal conductance of chloride. In contrast, with frame shift mutations there is complete loss of chloride conductance. In Becker’s disease there is likewise a defect of the muscle chloride channel (CLCN1), with a recessive mode of inheritance linked to chromosome 7q35. A variety of genetic defects have been described including more than 20 missense mutations, and deletions. Depending on the type of mutation there may be low or reduced opening of chloride channels, or there may be chloride efflux but not influx. A final type of congenital myotonia, myotonia levior, is autosomal dominant and again is related to a mutation of the CLCN1 channel. Laboratory: Laboratory tests are generally of limited value. CK is usually normal. Clinical syndrome Myotonia congenita (Thomsen) Myotonia congenita (Becker) Myotonia levior Pathogenesis ... - tailieumienphi.vn
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