diagnosis and investigation in primary care

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Diagnosis and investigation in primary care:

  • note that if potassium is <= 2.5 mmol/L urgent treatment (in a secondary care setting is required)
    • look for warning signs or symptoms
      • weakness or palpitations
      • changes on electrocardiography (ECG)
      • severe hypokalemia (less than 2.5 mEq per L [2.5 mmol per L])
      • rapid-onset hypokalaemia
      • underlying heart disease or cirrhosis (1)

In the absence of any evidence which warrants immediate treatment, a careful history and physical examination should be carried out:

  • history
    • always check for diuretics in the drug history - commonest single cause of hypokalaemia
    • if not on diuretics then hypokalaemia suggests potassium loss, consider
      • faecal loss: chronic diarrhoea e.g. - colitis, laxative abuse
      • vomit - due to any cause
      • skin e.g. burns, excessive sweating
    • history of excessive alcohol intake
    • any process which may stimulates uptake of potassium from the extracellular fluid into cells
      • intravenous insulin for treatment of hyperglycaemia (in particular, diabetic ketoacidosis)
      • stimulation of sympathetic β2 receptors (for example, with high dose salbutamol) 
      • verapamil overdose
      • after vitamin B12 or folate replacement in megaloblastic anaemia
    • a history of muscle weakness (typically after strenuous exercise or a large carbohydrate meal) and severe hypokalaemia may indicate:
      • hypokalaemic periodic paralysis or
      • thyrotoxic periodic paralysis (if symptoms of thyrotoxicosis are also present, particularly in Asian men)
  • physical examination
    • there may be flaccid muscle weakness and signs of arrhythmia
    • check for high blood pressure - hypokalaemia associated with raised blood pressure may indicate primary hyperaldosteronism or Cushing’s syndrome
    • presence of Kussmaul breathing, hypotension and signs of dehydration in a diabetic patient may suggest diabetic ketoacidosis (1,2,3)

Laboratory investigations

  • in mild hypokalaemia with an obvious cause
    • monitor serum potassium concentration
  • in moderate and severe hypokalaemia and when the cause is unclear
    • initial basic laboratory investigations should include -
      • serum electrolytes
      • serum  magnesium
        • hypomagnesaemia  often coexists with hypokalaemia and needs to be corrected for successful treatment of hypokalaemia
      • serum bicarbonate
        • to check for acid-base disturbances
      • serum glucose
      • urine potassium
        • to identify whether hypokalaemia is due to renal potassium loss
        • can be assessed by
          • a spot urine potassium
          • 24 hour urine potassium
          • transtubular potassium gradient
          • urine potassium:creatinine ratio (KCR) 
  • if spurious hypokalaemia is suspected
    • send a fresh blood sample to the laboratory (rapidly following venepuncture) for reanalysis of potassium (1)
  • persistent hypokalaemia of unknown cause will require further investigation and referral to secondary care. Some investigations may be requested from primary care such as:
    • U + Es
      • hypokalaemia
      • in Conn's syndrome, sodium may be mildly elevated or normal metabolic alkalosis
    • plasma renin and aldosterone - low renin and high aldosterone (raised aldosterone: renin ratio) suggests primary hyperaldosteronism - note that a normal or high renin may occur secondary to compensatory mechanisms
      • assess the effect of posture on renin, aldosterone and cortisol (measure at 9am lying and at noon standing) - this provides further information as to the cause of primary hyperaldosteronism
        • if reduced aldosterone and reduced cortisol on standing then ACTH dependent cause e.g. adrenocortical adenoma (Conn's syndrome)
        • if increased aldosterone and reduced cortisol then angiotensin-II dependent cause e.g. bilateral adrenocortical hyperplasia
    • cortisol - a morning plasma cortisol may be raised suggesting Cushing's syndrome
    • thyroid function tests (if thyrotoxic periodic paralysis is suspected) - serum thyroid stimulating hormone and free thyroxine)
  • ECG (1,2)


Last edited 03/2018 and last reviewed 04/2022