Endocrine Myopathies Research Articles

Myopathies of endocrine disorders: A prospective clinical and biochemical study.

Introduction:Major categories of endocrine myopathy include those associated with: Adrenal dysfunction (as in Cushing's disease or steroid myopathy); thyroid dysfunction (as in myxedema coma or thyrotoxic myopathy); vitamin D deficiency; parathyroid dysfunction; and pituitary dysfunction. Steroid myopathy is the most common endocrine myopathy.Objective:To study the etiology, varied presentations, and outcome after therapy of patients with endocrine myopathies.Materials and Methods:Myopathy was evaluated by the standard clinical procedures: Detailed clinical history, manual muscle strength testing, and creatine phosphokinase (CPK). Endocrine disorders were diagnosed as per clinical features and biochemical parameters. The treatment was given to patients as per underlying endocrine disease. Myopathy was assessed before and after treatment.Results:Out of the 37 patients who were diagnosed with endocrine myopathies, thyroid dysfunction was the most common cause (17 cases), followed by vitamin D deficiency in nine, adrenal dysfunction in six, parathyroid dysfunction in three, and pituitary dysfunction in two. Some patients had atypical presentation (repeated falls in one, tongue fasciculations in one, neck weakness in five, one with ptosis and facial weakness, asymmetrical onset in one, and calf hypertrophy in one. The serum creatine kinase (CK) concentration did not correlate with muscle weakness. Following the treatment regimen which was specific for a given myopathy, 26 patients recovered fully.Conclusion:We found varied clinical presentations of endocrine myopathies. All the patients with neuromuscular complaints should be investigated for endocrine causes because significant number of them recovers fully with specific treatment.

An intelligent model for two level diagnoses of neuromuscular diseases

In this paper, we have developed a intelligent model that performs two level diagnosis of neuromuscular diseases (NMDs) by using muscular, cognitive, psychological, internal lingual and EMG parameters. At first level, the NMDs are: muscular dystrophy, polymyositis, endocrine myopathy, metabolic myopathy, neuropathy, poliomyelitis and myasthenia gravis. These diseases are further classified in more specific diseases at second level. Data mining methods are used to obtain the important parameters/symptoms. A hierarchal rule base model is integrated with case base reasoning for calculating cumulative confidence factor (CCF) and confidence index. In addition to this a Bayesian network (BN) model is also developed for calculating the probability of occurrence of diseases and to make a comparative view of the results obtained by CCF and BN approaches.

Xin Is a Marker of Skeletal Muscle Damage Severity in Myopathies

Xin is a striated muscle-specific protein that is localized to the myotendinous junction in skeletal muscle. However, in injured mouse muscle, Xin expression is up-regulated and observed throughout skeletal muscle fibers and within satellite cells. In this study, Xin was analyzed by immunofluorescent staining in skeletal muscle samples from 47 subjects with various forms of myopathy, including muscular dystrophies, inflammatory myopathies, mitochondrial/metabolic myopathy, and endocrine myopathy. Results indicate that Xin immunoreactivity is positively and significantly correlated (rs = 0.6175, P = <0.0001) with the severity of muscle damage, regardless of myopathy type. Other muscle damage measures also showed a correlation with severity [Xin actin-binding repeat-containing 2 (rs = -0.7108, P = 0.0006) and collagen (rs = 0.4683, P = 0.0783)]. However, because only Xin lacked immunoreactivity within the healthy muscle belly, any detectable immunoreactivity for Xin was indicative of muscle damage. We also investigated the expression of Xin within the skeletal muscle of healthy individuals subjected to damaging eccentric exercise. Consistent with our previously mentioned results, Xin immunoreactivity was increased 24 hours after exercise in damaged muscle fibers and within the activated muscle satellite cells. Taken together, these data demonstrate Xin as a useful biomarker of muscle damage in healthy individuals and in patients with myopathy. The strong correlation between the degree of muscle damage and Xin immunoreactivity suggests that Xin may be a suitable outcome measure to evaluate disease progression and treatment effects in clinical trials.

Endocrine myopathies

Endocrine myopathies

Angeborene und endogene endokrine Myopathien

Disorders in endocrinological pathways rarely lead to manifest acquired or endogenous myopathy so that an interdisciplinary evaluation between neurology and endocrinology is essential for these disorders. Asymptomatic or forme fruste variants may be more common and even underdiagnosed in these circumstances. Dysbalance disorders of protein synthesis, electrolytes and carbohydrates can lead to several rare forms of myopathy due to the dependence on hormonal metabolism. In general, the main neuromuscular symptom is proximal weakness, sometimes in addition to myalgia and muscle atrophy. Endocrine myopathies are usually reversible by treatment of the underlying disease. The severity of the endocrinopathy is of fundamental importance for the long-term clinical outcome.

Camptocormia: the bent spine syndrome, an update

Camptocormia, also referred to as bent spine syndrome (BSS) is defined as an abnormal flexion of the trunk, appearing in standing position, increasing during walking and abating in supine position. BSS was initially considered, especially in wartime, as a psychogenic disorder. It is now recognized that in addition to psychiatric syndromes, many cases of reducible BSS have a somatic origin related to a number of musculo-skeletal or neurological disorders. The majority of BSS of muscular origin is related to a primary idiopathic axial myopathy of late onset, appearing progressively in elderly patients. Diagnosis of axial myopathy first described by Laroche et al. is based upon CT/MRI examination demonstrating massive fatty infiltration of paravertebral muscles. The non-specific histological aspect includes an extensive endomysial fibrosis and fat tissue with irregular degenerated fibers. Weakness of the paravertebral muscles can be secondary to a wide variety of diseases generating diffuse pathologic changes in the muscular tissue. BSS can be the predominant and sometimes revealing symptom of a more generalized muscular disorder. Causes of secondary BSS are numerous. They must be carefully assessed and ruled out before considering the diagnosis of primary axial myopathy. The principal etiologies include on the one hand inflammatory myopathies, muscular dystrophies of late onset, myotonic myopathies, endocrine and metabolic myopathies, and on the other hand neurological disorders, principally Parkinson's disease. Camptocormia in Parkinsonism is caused by axial dystonia, which is the hallmark of Parkinson's disease. There is no specific pharmacologic treatment for primary axial myopathy. General activity, walking with a cane, physiotherapy, and exercises should be encouraged. Treatment of secondary forms of BSS is dependent upon the variety of the disorder generating the muscular pathology. Pharmacologic and general management of camptocormia in Parkinson's disease merge with that of Parkinsonism. Levodopa treatment, usually active on tumor rigidity and akinesia, has poor or negative effect on BSS.

Diagnostic value of in situ muscle fiber conduction velocity measurements in myopathies.

In situ studies on muscle fiber conduction velocity (MFCV) were performed in 54 patients with histologically and biochemically defined myopathies. MFCV was measured over a 10 cm segment of the rectus femoris muscle by intramuscular stimulation and recording. Muscle disorders included muscular dystrophies, myotonic dystrophy, inflammatory myopathies, metabolic myopathies, endocrine myopathies, and congenital myopathies with structural abnormalities. Ten healthy volunteers served as controls. MFCV was significantly reduced in all patients except those with a defect in glycolysis and those that had recovered from acute myositis. MFCV did not vary with either sex. age or the duration of the disease. This shows that MFCV slowing is an unspecific finding in most myopathies. However, in some patients with normal needle electromyography, MFCV provided additional information in diagnosing muscle disease.

An integrated intelligent computing model for the interpretation of EMG based neuromuscular diseases

Intelligent computing system (ICS) and knowledge-based system (KBS) have been widely used in the detection and interpretation of EMG (electromyography) based diseases. Heuristic-based detection methods of EMG parameters for a particular disease have also been reported in the literature but little effort has been made by researchers to combine rule-based reasoning (RBR) and case-based reasoning of KBS, and ANN (artificial neural nets) of ICS. Integrating the methods in KBS and ICS improves the computational and reasoning efficiency of the problem-solving strategy. We have developed an integrated model of CBR and RBR for generating cases, and ANN for matching cases for the interpretation and diagnosis of neuromuscular diseases. We have hierarchically structured the neuromuscular diseases in terms of their physio-pyscho (muscular, cognitive and psychological) parameters and EMG based parameters (amplitude, duration, phase etc.). Cumulative confidence factor is computed at different node from lowest to highest level of hierarchal structure in the process of diagnosis of the neuromuscular diseases. The diseases considered are Duchenne muscular dystrophy, Polymyostits, Endocrine myopathy, Metabolic myopathy, Neuropathy, Poliomyletis and Myasthenia gravis. The basic objective of this work is to develop an integrated model of RBR, CBR and ANN in which RBR is used to hierarchically correlate the sign and symptom of the disease and also to compute cumulative confidence factor (CCF) of the diseases. CBR is used for diagnosing the neuromuscular diseases and to find the relative importance of sign and symptoms of a diseases to other diseases and ANN is used for matching process in CBR.

The clinical use of macro and surface electromyography in diagnosis and follow-up of endocrine and drug-induced myopathies

M.A. Minetto1,2, A. Rainoldi2,3, and J.F. Jabre4 1Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin; 2Laboratory for Engineering of the Neuromuscular System (LISiN), Department of Electronics, Polytechnic of Turin; 3Motor Science Research Center, SUISM, University of Turin, Turin, Italy; 4Department of Neurology, Boston University and Harvard Medical School, Boston VA Medical Center, Boston, MA, USA

Classification of endocrine ophthalmopathy

Based on the analysis of the classifications of endocrine ophthalmopathy (EOP), described in the literature and their many years' own observations of patients with this condition, the authors propose their classification. EOP is divided into 3 forms, 2 of which may be characterized by the compensation of a pathological process and by the stages of its development (from active cellular infiltration to end-stage fibrosis). The former of the forms (exophthalmic thyrotoxicosis) frequently regresses during endocrinological therapy. Edematous exophthalmos and endocrine myopathy may be complicated by an irreparable loss of visual functions and working capacity. These patients should be treated by ophthalmologists, by obligatorily keeping in mind the compensation of a pathological process and the stage of its development.

Neurologic Conditions Causing Lameness in Companion Animals

Animals presented with non-weight-bearing lameness are a diagnostic challenge for the veterinarian. It is extremely important to distinguish between orthopedic and neurologic causes of lameness, because the diagnostic and therapeutic plans can be quite different. Myopathies can be confused with orthopedic disease because of gait abnormalities and associated muscle pain. Common myopathies seen in companion animal medicine include polymyositis, muscular dystrophy, endocrine and infectious myopathies, and myasthenia gravis. Lameness caused by disease of the nerve root or nerve is confused with orthopedic disease because of the disturbances of a nerve's sensory distribution (nerve-root signature) or disruption of the motor innervation. The diseases of the nerve root or nerve discussed are lateralized intervertebral disk disease, spinal cord neoplasia, malignant peripheral nerve sheath tumors, and traumatic neuropathies. The diagnosis of these diseases requires careful attention to the signalment, a complete history, and a thorough physical examination focusing on the neurologic and orthopedic components. Ancillary testing should be selected based on these results and a minimum database. Electrodiagnostic testing, radiography, and advanced imaging may help to localize the lesion more precisely and sometimes to confirm the diagnosis. Surgical exploration and histopathology often provide the definitive diagnosis. These cases of non-weight-bearing lameness are a diagnostic challenge, but when successful resolution can be reached, it is gratifying to the clinician, client, and patient.

Osteoarticular disorders of endocrine origin.

Endocrine diseases may present with musculoskeletal complaints, and their outcome, even after endocrine control, can be impaired by bone and joint disorders. All musculoskeletal structures, including bone, cartilage, synovium, tendons and ligaments, can be involved by some processes triggered by the endocrine disorder and its related disturbances of homeostasis, including that of growth factors. Endocrine disorders may account for 20-30% of all cases of osteopenia or osteoporosis in adults, the main causes being central and peripheral hypogonadism, endogenous and exogenous hypercorticism or hyperthyroidism, and primary hyperparathyroidism. The physician should be aware of these identifiable and treatable causes of bone loss when interpreting bone mineral density measurements. It is also valuable to evaluate bone status in patients diagnosed with these endocrine disorders. Specific bone therapeutic measures could be discussed. Other frequent musculoskeletal features include myopathy and joint and soft tissue involvement. Endocrine myopathy is frequent in most of the endocrine disorders and is non-specific since proximal painless muscle weakness associated with normal serum enzyme levels and an uncommonly encountered electromyogram myopathic pattern are present in these diseases. Soft tissue involvement is also a frequent consequence of acromegaly, hypothyroidism and diabetes mellitus. There is also a risk of nerve entrapment syndromes in these conditions. Specific arthropathies are the hallmark of acromegaly at the spinal and peripheral joints. Neuroarthropathies are a severe complication of diabetes mellitus as a result of infection, neuropathy and vasculopathy. In all these settings, the physician should be aware that endocrine disorders are part of the differential diagnosis and, conversely, that these articular and peri-articular lesions should be managed independently of the control of the underlying endocrine condition, a specific outcome being borne in mind.

ENDOCRINE MYOPATHIES

This article provides a review of some of the muscular disorders that can arise from some of the commonly seen endocrinologic disturbances. Thyroid, parathyroid, and adrenal dysfunctions as they relate to neuromuscular symptoms are discussed. Common clinical presentations of the endocrine myopathies are highlighted, along with diagnostic evaluation and treatments.

Studies on enterovirus in patients with chronic fatigue syndrome.

A large study on 121 patients with the chronic fatigue syndrome (CFS) that examined muscle biopsy samples for enterovirus by means of polymerase chain reaction analysis was carried out. The results were compared with those obtained from 101 muscle biopsy specimens from patients with a variety of other neuromuscular disorders (OND), including neurogenic atrophies, dystrophies, and mitochondrial, metabolic, and endocrine myopathies. Thirty-two (26.4%) of the biopsy specimens from the group of patients with CFS were positive, compared with 20 (19.8%) from the group of patients with OND, a difference that was not significant. This finding is in contrast to those of our previous smaller study in which significantly more patients with CFS than control subjects (53% [32 of 60] vs. 15% [6 of 41]) had enterovirus RNA sequences in their muscle. It was concluded that it is unlikely that persistent enterovirus infection plays a pathogenetic role in CFS, although an effect in initiating the disease process cannot be excluded.

The Pentose Phosphate Pathway in Skeletal Muscle Under Patho-Physiological Conditions: A Combined Histochemical and Biochemical Study

Over the last 30 years, research into the neuromuscular apparatus, has expanded greatly. Multidisciplinary investigations have rapidly advanced our understanding both of diseases and of the basic neuromuscular mechanisms. The mode of pathological reaction of the neuromuscular apparatus is now quite well understood. The most notable aspect of the reaction of the injured neuromuscular apparatus is the remarkably stereotyped character of the resulting pathological changes as demonstrated by a wide variety of harmful causes, producing surprisingly similar effects. The findings of our combined histochemical and biochemical investigations presented in this monograph, are in complete harmony with the stereotyped character of the pathological changes. For example, it is particularly striking that many affected muscle fibres of patients with muscular dystrophies, congenital myopathies, inflammatory myopathies, metabolic myopathies, endocrine myopathies, or with diseases of the lower motor neuron, display an enhanced activity of both oxidative enzymes of the pentose phosphate pathway. Likewise, we found that experimental animals with disordered skeletal muscles, provoked by different types of agents or treatments, reveal the same marked rise in activity of GPDH and PGDH in the muscle fibres, with a positive correlation between the activity of both enzymes. Other findings of our investigations point to a positive correlation between the activity of GPDH and PGDH on the one hand and that of the non-oxidative enzymes of the pentose phosphate pathway, the enzymes TA, TK, RPI and RPE on the other hand. The rise in activity of PGDH and, in particular, of GPDH is regulated by two different mechanisms. The first represents a rapid control mechanism based on the stimulation of both oxidative enzymes of the pentose phosphate pathway by NADP+ and on their inhibition by NADPH. The other mechanism represents a long-term effect directed at the synthesis of the enzymes. It is this type of mechanism which is responsible for the rise in activity of GPDH and PGDH we observed. The findings obtained with the applied enzyme histochemical techniques clearly demonstrated that the rise in activity of both enzymes is not homogeneously distributed in the disordered skeletal muscles of man and experimental animals. For that reason, in order to obtain reliable quantitative information about enzyme activities in the muscle fibres themselves, the application of biochemical assays on a micro-scale was indispensable. The biochemical assay of enzyme activities was performed on histologically and histochemically selected dissected muscle specimens.(ABSTRACT TRUNCATED AT 400 WORDS)

Serum Enzymes in Disease of Skeletal Muscle

Creatine kinase is the serum enzyme that shows the greatest frequency of abnormality in skeletal muscle disease. Changes in this enzyme in sex-linked dystrophy (Duchenne's and Becker's) patients and carriers; in patients with other dystrophies; and in inflammatory, toxic, endocrine, and traumatic myopathy are reviewed. The changing role of serum enzyme measurements as a consequence of newer methods of genetic diagnosis is also considered.

Evaluation and Differential Diagnosis of Fibromyalgia: Approach to Diagnosis and Management

SUMMARY The combination of widespread musculoskeletal pain, high tender point count, and nonrestorative sleep are sufficient criteria for the diagnosis of fibromyalgia. The condition is primary in the absence of underlying disease and is considered concomitant or secondary when closely associated with another organic disease. Despite more simplified diagnostic criteria, the work-up for fibromyalgia must always be directed toward excluding the underlying causes. In addition to general and rheumatic history and physical examination and selected laboratory studies, careful attention to defining any existing sleep and mood disturbances is important in designing a management program. Although 46 medical conditions have been associated with fibromyalgia, a practical differential diagnostic list includes polymyalgia rheumatica, myofascial pain, connective tissue disease, endocrine myopathies, psychoneuroses, and other chronic fatigue syndromes.

Endocrine ophthalmopathies: Problems of rational classification

Results of a study of the clinical picture of endocrine ophthalmopathies in 1710 patients are presented. On the basis of the clinical course of endocrine ophthalmopathy and by comparison with histological findings in extra-ocular muscles, it was possible to distinguish three principal forms of the disease: thyrotoxic exophthalmos, edematous exophthalmos and endocrine myopathy.

Endocrine Myopathies

The atrophy produced by endocrine disorders is primarily due to alterations in protein and carbohydrate metabolism. Type II muscle fibers are more severely affected than are Type I fibers. Steroid myopathy and the myopathy associated with excess ACTH have a typical pattern of proximal weakness affecting the legs more than the arms. Steroid myopathy is usually not apparent until other signs of glucocorticoid excess are present. Treatments of steroid myopathy are as follows: Lower the dose of steroid, use a nonfluorinated glucocorticoid, and exercise or physical therapy. Adrenal insufficiency produces generalized weakness, muscle cramping, and fatigue in 50 per cent of patients. Some patients also develop hyperkalemic paralysis. The treatment is hormone replacement. Thyrotoxicosis produces myopathy caused by net protein catabolism, accelerated basal metabolic rate and impaired carbohydrate metabolism. Shortening of contraction time may result from accelerated myosin ATPase activity and enhanced calcium uptake by the sarcoplasmic reticulum. Depolarization of the muscle fiber and impaired Na-K activity in muscle may predispose to thyrotoxic periodic paralysis. Neuromuscular presynaptic impairment may account for the worsening of myasthenia gravis by thyrotoxicosis. In hypothyroidism, impaired energy metabolism may limit force generation. Slow contraction and relaxation reflect reduction in myosin ATPase activity and impaired calcium uptake by the sarcoplasmic reticulum. Treatment for thyroid-associated muscle disorders is restoration of a euthyroid state. Muscle weakness associated with hypopituitarism is due to loss of thyroid and adrenal cortical hormones. Children require growth hormone for muscle development. T3 and growth hormone synergize to maintain normal protein synthesis. Primary and secondary hyperparathyroidism and osteomalacia are often associated with proximal weakness and fatigability. The myopathy improves with restoration of normal PTH levels and vitamin D replacement. Hypoparathyroidism and pseudohypothyroidism are associated with tetany. Tetany is worsened by alkalosis and is treated by calcium and magnesium replacement.

Muscle dysfunction in male hypogonadism.

Twenty-eight consecutive male patients with primary and secondary hypogonadism (14 each) were evaluated clinically and electrophysiologically for muscle dysfunction. Although generalised muscle weakness was initially reported by only 9 patients, on direct questioning, it was recorded in 19. Objective weakness was found in 13 patients and it involved both the proximal and distal limb muscles. Quantitative electromyography showed evidence of myopathy in the proximal muscle in 25 patients, i.e., reduced MUP duration and amplitude with increased polyphasia in the deltoid and the gluteus maximus. There were no denervation potentials. None of the patients showed clinical neuropathy or NCV abnormalities. Thus, the profile of muscle involvement in hypogonadism closely simulates limb-girdle muscular dystrophy and other endocrine myopathies. The incidence of muscle involvement was higher in secondary hypogonadism. Diminished androgens in primary hypogonadism and diminished growth hormone in the secondary hypogonadism are probably responsible for the myopathy.