Diagnosis and investigation in primary care

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:
  • Urine studies
  • 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)
• imaging of the adrenal glands (CT or MRI) if there is suspicion of mineralocorticoid, glucocorticoid or catecholamine excess (4)
• MRI of the pituitary gland (to exclude Cushing's disease) (4)

Reference:

• (1) McDonald TJ, Oram RA, Vaidya B. Investigating hyperkalaemia in adults. BMJ. 2015;351:h4762.
• (2) Kim MJ, Valerio C, Knobloch GK. Potassium Disorders: Hypokalemia and Hyperkalemia. Am Fam Physician. 2023 Jan;107(1):59-70.
• (3) Pepin J, Shields C. Advances in diagnosis and management of hypokalemic and hyperkalemic emergencies. Emerg Med Pract. 2012;14(2):1-17
• (4) Kardalas E, Paschou SA, Anagnostis P, Muscogiuri G, Siasos G, Vryonidou A. Hypokalemia: a clinical update. Endocr Connect. 2018 Apr;7(4):R135-R146. doi: 10.1530/EC-18-0109.