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A young woman with muscle weakness

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Q1: What is the provisional diagnosis and how will you confirm it?

The characteristic features of muscle pain, a predominant proximal muscle weakness, sluggish ankle jerks, and absence of sensory involvement suggests a primary muscle involvement, that is, a myopathy.

To confirm the diagnosis of a myopathy, biochemical tests such as estimation of serum transaminases, lactic acid dehydrogenase (LDH), aldolase, and creatine kinase are very useful. Of these, the analysis of creatine kinase levels is the most sensitive indicator and measure of muscle damage. Electrodiagnostic tests especially an electromyogram (EMG) are of great value in the diagnosis of muscle disorders. A muscle biopsy can be of great diagnostic value in certain muscle storage disorders, denervative disorders, mitochondrial myopathies, polymyositis, and in some muscle dystrophies.

The laboratory investigations of this patient summarised in box 1 reveal a markedly raised creatine kinase and LDH levels and an EMG pattern all confirming the diagnosis of a myopathy.

Box 1: Laboratory investigations (normal laboratory range in parentheses)

  • Serum cholesterol: 6.0 mmol/l (<5.2)

  • Serum creatinine: 88.4 μmol/l (53.0–88.4)

  • Aspartate aminotransferase: 88 IU/l (<30)

  • Alanine aminotransferase: 70 IU/l (<30)

  • LDH: 2500 IU/l (0–150)

  • Creatine kinase (total): 1795 IU/l (0–100)

  • EMG: reduced amplitude of muscle unit potentials

  • Muscle biopsy: normal

Q2: What are the causes of this condition?

Muscle disorders are classified syndromically into acute or subacute, chronic, and episodic depending upon the onset and progress (see box 2).

Box 2: classification of muscle diseases

Acute/subacute onset
  • Idiopathic polymyositis/dermatomyositis.

  • Viral polymyositis.

  • Botulism.

  • Organophosphorus poisoning.

Chronic onset
  • Muscle dystrophies.

  • Chronic polymyositis.

  • Endocrine myopathies.

  • Mitochondrial and other congenital myopathies.

  • Storage disorders.

Episodic
  • Periodic paralysis.

  • Myasthenia gravis.

  • Exercise intolerance.

Pain and tenderness associated with muscle disorders are characteristic of a few specific disorders listed in box 3.

Box 3: Muscle disorders with pain/tenderness

  • Connective tissue disorders: lupus erythematosus, polymyositis, polyarteritis nodosa, Sjögren's syndrome, mixed connective tissue disease.

  • Localised multifocal fibrositis.

  • Trichinosis.

  • Myopathy of myoglobinuria and McArdle's syndrome.

  • Viral polymyositis.

  • Hypothyroidism.

Q3: What is the most probable aetiology in this patient and what further investigations would you order to document it?

In this young woman with myopathy, a history of weight gain, and bradycardia on examination, an endocrine myopathy, especially hypothyroidism, must be excluded. Also, connective tissue disorders such as polymyositis and lupus erythematosus should be ruled out with appropriate investigations.

Q4: The special laboratory investigations of the patient are summarised on p 274. What is the final diagnosis?

Raised TSH along with a low triiodothyronine confirm the diagnosis of hypothyroidism. The presence of anti-TPO antibodies provides conclusive evidence of an autoimmune thyroid disease with resultant hypothyroidism.

The patient was given thyroxine replenishment and there was marked symptomatic improvement and the creatine kinase, LDH, and TSH levels returned to normal.

Discussion

Hypothyroidism is associated with a wide range of muscle disturbances varying from myalgias, to a true myopathy to rhabdomyolysis.1 2 Two classic syndromes of hypothyroid muscle disorders have been described: the Kocher-Debré-Sémélaigne syndrome (cretinism associated with myopathy) and Hoffmann's syndrome (myxoedema in childhood or adult life associated with muscle hypertrophy). The muscle disorders usually occur in the setting of an established chronic hypothyroid state, though rarely, they may occur in acute hypothyroidism as well.3

Myopathy as the sole presenting feature of hypothyroidism, without the other typical signs and symptoms of hypothyroidism, as seen in this patient, is however unusual. Most such cases have been found to be of autoimmune origin.4

Impaired energy metabolism that limits force generation, a reduction in the myosin ATPase activity reflected by the slow contraction and relaxation of the reflexes, and an impaired calcium uptake by the sarcoplasmic reticulum are the proposed pathogenetic mechanisms of muscle weakness in hypothyroidism.5

Box 4: Learning points

  • Though unusual, myopathy may be the presenting feature of hypothyroidism.

  • All patients with a myopathy of obscure origin should be investigated to exclude disorders like hypothyroidism.

The spectrum of structural changes in the skeletal muscles in hypothyroid myopathy is a continuum. The changes in muscle biopsy correlate with the severity of hypothyroidism and consist of increasing type 2 fibre atrophy and central nuclear counts on light microscopy, and excessive glycogen accumulation and increased numbers of mitochondria on electron microscopy. The changes on muscle biopsy also depend on the amount of tissue available for assessment.6

Substitutive therapy with thyroxine is used in the treatment of hypothyroid myopathy. Marked improvement in symptoms and laboratory parameters occurs on attainment of an euthyroid state. The present patient was unusual in that she presented with only features of a primary muscle disorder without pointers to an underlying hypothyroid state. The learning points from this case are summarised in box 4.

Final diagnosis

Autoimmune thyroid disease, hypothyroidism, and hypothyroid myopathy.

References

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