Investigations

1st investigations to order

clinical diagnosis

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Most people presenting with cramps have idiopathic cramps, which are usually diagnosed following clinical exam. Further investigations are only required if the cramp has atypical features or other associated conditions are suspected.

Result

commonly diagnosed on history and clinical exam

Investigations to consider

serum or urine hCG

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Performed to verify or rule out pregnancy as a possible association with muscle cramps.

Result

elevated in pregnancy

fasting serum metabolic panel

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Possible derangements include elevated or low potassium, sodium, magnesium, or calcium. Check ionised calcium if serum albumin is low.

Hyperphosphataemia in patients with end-stage renal disease enhances cramps, particularly during dialysis sessions in patients undergoing haemodialysis.

Elevated fasting blood sugar seen in diabetes.

Result

may show electrolyte abnormality or diabetes

thyroid-stimulating hormone (TSH)

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Indicated to verify hypo- or hyperthyroidism. Further thyroid function tests may be warranted.

Elevated TSH is consistent with primary hypothyroidism.

Suppressed TSH is consistent with hyperthyroidism.

Both are occasionally associated with cramping illness.

Result

abnormal in thyroid dysfunction

HbA1c

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May be suggestive but not confirmatory for hypoglycemia.

Result

lower than expected value in relation to observed control via fingerstick blood glucose may suggest hypoglycaemia in diabetes

serum liver function tests

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Performed to assess degree of hepatic impairment.

Cramps are associated with presence of advanced cirrhosis (e.g., Child-Pugh class C liver disease).

Result

elevated liver enzymes in hepatic disease; may be normal in advanced cirrhosis

prothrombin time (PT) and INR

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Performed in people with suspected or known liver disease and cramps.

Prolonged PT and elevated INR are associated with severe cirrhotic liver disease, which is associated with cramps.

Result

will usually be abnormal in severe hepatic disease

serum myoglobin and urinalysis

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Elevated serum myoglobin with myoglobinuria, presenting with prominent muscle pain, should be considered in the differential diagnosis.

Urinalysis will help to determine whether a urine myoglobin test is needed (i.e., haem-positive with no RBCs on microscopy).

Result

present if muscle pain associated with myoglobin release and excretion

serum creatine kinase (CK)-MM

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Indicated only if history and/or physical examination suggests a potential primary muscle disease or patient is taking a statin.

In idiopathic muscle cramps, this should be normal. However, muscle cramps alone can precipitate increased serum CK concentrations. This does not necessarily imply a primary muscle disease as the aetiology.[83]

May be high levels of serum CK-MM in severe EAMC disease.

Elevated CK during statin therapy may indicate genetic predisposition to malignant hyperthermia.[84]

Chronic elevation of serum CK is not uncommon in familial muscle contraction syndromes (particularly glycogen storage disease, muscular dystrophy) and haemodialysis, both of which are commonly associated with muscle cramps.[85][86]

Beta-blockers with intrinsic sympathomimetic activity (such as pindolol, carteolol) can cause a chronic elevation of CK. These agents are among the drugs most frequently associated with causing muscle cramps. However, no correlation is seen between muscle cramp frequency/severity and the serum CK concentrations associated with them.[51]

Result

normal; may be elevated in severe exercise-associated muscle cramps (EAMC)

serum alpha-tocopherol (vitamin E)

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May be performed if considering preventative therapy in people with cramps associated with cirrhosis.

Result

may be low in cirrhosis

serum zinc

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May be performed if considering preventative therapy in people with cramps associated with cirrhosis.

Result

may be low in cirrhosis

electromyogram

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Performed only in difficult-to-diagnose cases or if lower motor neuron disease is suspected.

Result

motor unit hyperactivity

nerve conduction studies

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Performed if lower motor neuron disease suspected.

Result

lower motor neuron disease: may show loss of amplitude of maximal compound muscle action potential or slowed conduction velocity or conduction block; sensory nerves are unchanged

serum aldolase

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Indicated only if history and/or physical examination suggests a potential primary muscle disease.

In idiopathic muscle cramps should be normal.

Result

normal

muscle biopsy

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Indicated only if history and/or physical examination suggests a potential primary muscle disease.

A normal biopsy demonstrates fibres roughly equal in size, tightly opposed to each other, no fibrous tissue separating them, nuclei peripherally situated.[87]

Result

usually normal; lower motor neuron disease: may be evidence of denervation, group atrophy, fibre type grouping; may be evidence of primary muscle disease

genetic studies

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Generally requested only when a patient's symptoms are particularly difficult to diagnose or a familial cramping syndrome is suspected (e.g., muscular dystrophy, congenital myotonia, glycogen storage disease, continuous muscle fibre activity syndrome, Satoyoshi's syndrome, Schwartz-Jampel syndrome, or Brody's disease).

Result

normal or genetic abnormality of associated familial cramping condition

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