Along with hereditary myopathies, there are many exogenic (the same a not hereditary) muscle affections due to the pathology of endocrine gland’s functioning. These forms of muscle pathology are called endocrine myopathies. In the cases of thyroid gland hyperfunction (the same a thyrotoxicosis), different regions of neuromuscular system may be involved in the pathological process. Thyrotoxic myopathy (TM) which is a subject of this investigation, occupies one of the first places between thyrotoxic (the same a thyrotoxicosis) neuromuscular affections. Meanwhile, for a long time in literature there was no clarity about the degree of muscle weakness and atrophy to diagnose TM in a patient. It’s because of the fact that the majority of patients complain of increased fatigue and general weakness due to thyrotoxicosis. In present time TM diagnostics is very rare. TM is a phenocopy (the clinical similar) of many neuromuscular diseases. However in literature, the data about peculiarities of clinical picture of TM is almost completely absent, it isn’t known about the frequency of affection of the isolated muscles or muscle groups, the topography of muscle weakness and successive involvement of isolated muscles in the pathological process during different stages of thyrotoxicosis and myopathy. The questions of differential diagnosis with similar neuromuscular disorders are described very poorly. In present article, we accent our attention at the clinical differentiation of the TM with other neuromuscular diseases, namely muscular dystrophy, myasthenia gravis, polymyositis, Addison’s disease, proximal spinal muscular atrophy, steroid myopathy and neurosis. In our opinion, the early diagnosis of TM may help the diagnosis of thyrotoxicosis in patients who have no classical clinical signs of this disease, i.e. in patients with latent thyrotoxicosis.
Side by side with hereditary types of myopathy, there is a special class of muscular affections that were influenced by the disturbances of endocrine glands. Thyrotoxic (the same a thyrotoxicosis) myopathy (TM) is found oftener than the other thyroid neuromuscular disease (encephalomyelopathy (simultaneously affection of brain and spinal cord), polyneuropathy, exophthalmic ophthalmoplegia (In ophthalmic Graves’ disease, the commonest of exophthalmic ophthalmoplegia-Bannister R. Brain and Bannister’s Clinical Neurology, 7 Ed., Oxford 1992, p.53), hypokalemic paralysis, myasthenia syndrome, syndrome amyotrophic lateral sclerosis (syndrome ALS), cerebellar ataxia). In 1938, TM was picked out as an independent nosological type [
All said is the reason of the fact that the research of neuromuscular system of patients having TM does not take place and myopathy is not diagnosed. Meanwhile if to arrange a special clinical research it can distinguish 61% - 81.5%, if to use electromyography, 92.6% - 100% of TM patients can be picked out [
We studied the results of research of 263 TM patients, 47 men and 216 women (151 cases of our own investigations and 112 published in medical literature). The clinical characteristic of TM patients and methods of research were described by us earlier [
A severe type of TM is managed to be diagnosed when there are well-known signs of thyrotoxicosis increasing of thyroid gland, exophthalmos and tachycardia). Real difficulties arise in cases when thyrotoxicosis develops latently and the patient did not have any goiter and exophthalmos. In this situation the appearance of muscular affections could be considered as a neuromuscular disease that is not connected with thyrotoxicosis. It is considerable difficult represent to diagnose a light degree of myopathy, especially at elderly people: the appearance of weakness and atrophy can be considered as age changes. There is opinion [
According to the clinical data and morphological changes in muscles and electromyography as well TM is a phenocopy (the clinical similar) of some hereditary and unhereditary (not hereditary) neuromuscular diseases. It is very important to distinguish this exogenous myopathy from similar diseases as the treatment leads to almost a complete regress of TM; consequently timely diagnosis is vitally necessary. In cases when special treatment of TM is not done, the muscular weakness increases, the patient cannot move by himself (the same an independent). Very severe changes weakness of bulbar [
A group of diseases with which it is necessary to differentiate TM is defined with the degree of its expressiveness. Severe types with the expressed atrophy of muscles it is necessary to distinguish from muscular dystrophies, paraneoplastic myopathy, proximal spinal muscular atrophy and diabetic proximal amyotrophy (atrophy proximal muscles); when we mention bulbar affections we should distinguish it from polymyositis, Addison’s disease and steroid myopathy.
We can find out phenotypically similarity of TM with limb-girdle variants of muscular dystrophy [
In patients having muscular dystrophy feel weakness of muscles that comes after atrophy (excluding pseudohypertrophic muscles are exceptions). TM patients have “weak” muscles that keep very often normal volume and muscle being atrophied keeps muscular force in a considerable degree. Such disproportion between the degree of weakness and atrophy of muscles is a very important sign of TM. To our mind, the disappearance of subcutaneous fatty tissue created false impression of severe atrophy of the muscle. With this fact, it is connected with another important clinical sign. This is extraordinary skin folding in the field of the muscle that was affected, especially the triceps brachii and quadriceps femoris muscles. It was these muscles that keep the full strength but seems to be most atrophied. Patients suffering of muscular dystrophy do not have the phenomenon of considerate skin folding above the muscle that was affected been if there is no muscular venter at all. It is necessary to add that deep reflexes in patients with muscular dystrophy lessen very early and disappear were as they remain normal or increase at TM patients.
Some TM patients have weakness of proximal and distal muscles and simultaneously bulbar muscles are found to be affected [
Great difficulties arise to differentiate of TM and idiopathic polymyositis [
The investigation of thyroid gland function (level of thyroid hormones in blood, antibodies in thyroglobulin and thyroid peroxidase, level absorption of radioactive isotope I131 of thyroid gland) is of great differential diagnostic significance and helps either to support or reject the diagnosis of TM. The study of creatinkinase (creatine kinase) level, antinuclear and Jo-1 antibodies in blood and electromyogram will be useful as well.
If with the help of regular research methods it is impossible to diagnose of thyrotoxicosis and the clinical data witness in favour of TM, then ex juvantibus can be prescribed methylthiouracil with the next definition of creation level in whole day urine. If big doses of methylthiouracil (80 gr/day) are prescribed to TM patients they arise considerable decrease or disappearance of creatinuria during several days [
As we marked, one of the clinical peculiarities of TM can be considered predominate of weakness over atrophy of certain muscles, presence of a typical “formula” of muscle affections (weakness) in the early and latent phase of the disease. This differs TM from Addison’s disease: at the latter one can mark progressive fatiguability transferring into a sharp general adinamia but at TM patients weakness is combined with motor excitation, lively facial expression and gesticulation. Another important signs of Addison’s disease are skin hyperpigmentation, painful spasms of the belly muscles, painful flexor muscular contractures, provoked by the affection of tendons and ligaments.
The clinical signs of muscular affections arising at steroid therapy may remain similar signs TM has. We observed some patients who had weakness and atrophy of pelvic girdle and hip muscles against the background of treatment by prednisolone in case of collagenous disease [
The level of sugar in blood can be increased at thyrotoxic patients. Sometimes the development of thyrotoxicosis could be complicated with the joining of sugar diabetes. At the same time sugar diabetes patients are known to have weakness and atrophy of muscles of proximal parts of extremities especially of legs and pelvic girdle muscles. Such affections got the name of proximal diabetics amyotrophy (atrophy proximal muscles). Unlike from TM very often one can expose asymmetry of muscular affections, involvement of distal parts of extremities in the process, myalgia (lumbalgia, ischialgia), lumboischialgia, paresthesia, light affections of sensitivity in wrists and feet.
Pathological muscular fatiguability and weakness are characteristic signs of severe myasthenia. This disease differs from TM by some clinical peculiarities. Muscular weakness at TM patients constant by its character carries away only certain muscles. When a patient has myasthenia his muscular weakness is more generalized and increases under a very little physical load to a degree when it becomes impossible to carry out physical job. This is the reason of variation of expressiveness of different symptoms during a day. The characteristic features of myasthenia are ptosis, diplopia and restricted movements of eyes balls upwards and outwards, dysarthria, dysphagia, dysphonia and amimiya (the same-absent facial expression). TM can be complicated by the weakness of bulbar muscles. However we cannot expose in TM the weakness of the external eyes muscles and “dropping” of the lower jaw as well because of the expressed weakness of the chewing muscles (mm. masseters).
Combination of TM with exophthalmic ophthalmoplegia is observed seldom [
The majority of patients having thyrotoxicosis disease have the signs neuroses-like state: effective emotional instability, tears-coming, fouling or trouble, fussiness, quick psychiatric fatiguability, depression and oppression of psychics and euphoria. In connection with this one of the mostly commonly-used mistakes in differentiating TM is the diagnosis of functional disorder of nervous system. There is common opinion that very often the patients with thyrotoxic disease complain of the weakness that is the consequence of the increased fatiguability and of exhaustion of psychiatric nature (i.e. asthenia). As a result of this, there are no investigations of the state of muscular function; possibility of affected skeletal muscles in the genesis of weakness is not taken into consideration. Meanwhile at the very early stage, TM can be diagnosed using different clinical criteria [
1) “Formula” of distribution of muscle weakness including iliopsoas (and gluteus maximus) muscles, interosseus volaris and lumbricales (interossei palmaris and lumbricales) muscles and/or flexors of neck muscles;
2) Atrophy of triceps brachii and quadriceps femoris muscles without decreasing their strength;
3) Extraordinary skin folding above these muscles.
Complaints and anamnesis collected with this purpose, use of simple clinical tests for exposing different movement affections (getting up from the squat position and from a low chair, from the lying-on-the back position etc.) help to make it objective the presence of muscular weakness and consequently, to avoid the false diagnosis neuroses. Some regression muscular affections against the background of antithyroid therapy as seen as the function of thyroid gland is being normalized confirm TM diagnosis.
The offered criteria and first of all the peculiarities of muscle affections give the opportunity to think thyrotoxicosis disease before its clinical appearances, because TM can be in many cases the earliest sign of developing thyrotoxicosis disease. Thus muscular affections can be additional clinical criteria of early diagnostics of thyrotoxicosis disease.
In terms of the using treatment of patient suffering thyrotoxic disease with the appearance of myopathy, this treatment according to the data of medical literature and our experimental study is actually a pathogenic one and its effectiveness is defined by this [
Taking into consideration the theoretical preconditions about the participation of cyclic nucleotides and Ca++ in the pathogenesis of muscular weakness at TM patients [
All authors agree with the content of the manuscript and there are no conflicts of interests between them.
Kazakov, V., Skoromets A., Stuchevskaya, T., Rudenko, D. and Kolynin, V. (2017) Differential Diagnosis of Thyrotoxic Myopathy. Open Journal of Molecular and Integrative Physiology, 7, 25-33. https://doi.org/10.4236/ojmip.2017.72002