1. Aetiology and classification 

Hyponatraemia is usually defined as a plasma sodium concentration of less than 135mmol/l and is commonly found in both primary and secondary care. It has a heterogeneous range of causes and, while in some cases an obvious precipitant is easily identified, in others elucidating the underlying diagnosis is a real challenge.

Hyponatraemia is most readily classified according to the extracellular volume status of the affected patient, as hypovolaemic, euvolaemic or hypervolaemic.

Hypovolaemic hyponatraemia
In hypovolaemic hyponatraemia, sodium is lost in greater quantities than water. Most commonly this occurs from the gut during episodes of diarrhoea or vomiting, or from the kidneys in patients on diuretic therapy or with Addison's disease (depletional hyponatraemia). In euvolaemic and hypervolaemic patients, hyponatraemia reflects an excess of total body water causing dilution of sodium (dilutional hyponatraemia).

Euvolaemic hyponatraemia
In patients who are euvolaemic, this can be secondary to adrenocorticotrophic hormone (ACTH) deficiency (for example in pituitary disease), hypothyroidism, primary polydipsia or the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The causes of SIADH are numerous.

Hypervolaemic hyponatraemia
Hypervolaemic hyponatraemia is usually a consequence of congestive cardiac failure (CCF) or portal hypertension.

Sodium levels
Mild hyponatraemia (130-135mmol/l) is often asymptomatic.

At lower concentrations, the symptom complex is determined both by the rate of fall of the plasma sodium and its absolute level.

Patients can usually tolerate a gradual fall in plasma sodium to around 125mmol/l without significant symptoms. If plasma sodium falls rapidly and/or the concentration falls below 125mmol/l, symptoms of nausea and lethargy occur, followed by headache and confusion.

In the most severe of cases, seizures, coma, brain damage and death can result.

Syndrome of inappropriate ADH secretion

  • Malignancy, for example small-cell lung cancer and lymphoma.
  • Intra-thoracic diseases, for example pneumonia, TB and lung abscesses.
  • Intra-cranial disorders, for example subarachnoid haemorrhage, infections and tumours.
  • Drugs, for example SSRIs, tricyclic antidepressants, phenothiazines, carbemazepine and cyclophosphamide.


  • Hyponatraemia.
  • Urine osmolality inappropriately high (>100mOsm/kg).
  • High urine sodium (>30mmol/l).
  • Normal renal, adrenal and thyroid function.

Further investigations

  • Depend on clinical presentation.
  • Consider chest X-ray, CT thorax and/or brain.


  • Treat underlying cause.
  • Fluid restriction <1 litre/day.
  • Demeclocycline, if above ineffective.

2. Making a diagnosis

The clinical history may suggest an underlying cause and, in particular, a full drug history is mandatory. A personal or family history of autoimmune disease may accompany a diagnosis of hypothyroidism or Addison's disease.

Respiratory symptoms, or a history of smoking, should alert to the possibility of an underlying bronchogenic neoplasm. There may be a psychiatric history in patients with primary polydipsia.

The most important aspect of the examination is to determine the extracellular fluid volume status of the patient, so assessment of skin turgor, jugular venous pressure and peripheral oedema are necessary.

Postural hypotension is a feature of volume depletion and, rarely, ACTH deficiency. There may also be clues to the underlying cause such as stigmata of chronic liver disease or the buccal and skin crease pigmentation of Addison's disease.

Difficulty in diagnosis
In theory, diagnosing the underlying cause of hyponatraemia should be easy. In practice, however, patients often do not fall into neat categories.

Determining that a patient is volume deplete or overloaded is straightforward if they are grossly dehydrated with reduced skin turgor, dry mucosae and postural hypotension, or have marked peripheral oedema.

However, more often than not, the signs are more subtle and it can be a challenge to confidently establish volume status by clinical means alone. Moreover, urine sodium concentrations may be borderline and consequently difficult to interpret.

Measuring the concentration of sodium in a spot specimen of urine is the most useful investigation to narrow down the differential diagnosis of hyponatraemia (see figure).

Plasma osmolality is not a discriminatory investigation, because it is low whatever the aetiology of hyponatraemia.

In SIADH, where there is autonomous production of antidiuretic hormone (ADH), urine osmolality is inappropriately elevated for the prevailing plasma sodium concentration.

Other investigations should be determined by the volume status of the patient and the urine sodium. It is important to remember that SIADH is a diagnosis of exclusion and should only be 'diagnosed' in euvolaemic patients with high urine sodium, who are known to have normal adrenal and thyroid function.

3. Management

Patients should be referred for urgent specialist review if hyponatraemia is acute (<48 hours duration), severe (<125mmol/l) and/or associated with symptoms. Non-urgent referral to an endocrinologist should be considered in asymptomatic patients without an obvious diagnosis.

Mild hyponatraemia (>130mmol/l), especially when there is a clear drug precipitant, may simply require monitoring alone. In moderate or severe cases, the underlying cause should be treated where possible, for example glucocorticoid and mineralocorticoid replacement in Addison's disease or levo-thyroxine therapy in hypothyroidism.

The plasma sodium concentration should be corrected at a rate of not more than 10mmol/l over a 24-hour period. Over-rapid correction may precipitate central pontine myelinolysis, a demyelinating disorder that can result in irreversible brain damage and death. More rapid correction of the plasma sodium is justified if the patient has severe symptoms and/or the hyponatraemia has developed over less than 48 hours.

Treatment of hypovolaemic hyponatraemia involves stopping any offending diuretic treatment and administering oral or intravenous fluids.

The mainstay of treatment of SIADH is fluid restriction (to <1 litre/day). If patients are unable to tolerate fluid restriction, demeclocycline, which acts on the kidney to inhibit ADH action, may be commenced, but it can cause photosensitive skin reactions.

Oral vasopressin receptor antagonists are in development and may have a future role in the management of SIADH and in hypervolaemic hyponatraemia.

Contributed by Dr Rachel Williamson, clinical research fellow and Dr Mark Strachan, consultant endocrinologist, Western General Hospital, Edinburgh.

Have you registered with us yet?

Register now to enjoy more articles and free email bulletins


Already registered?

Sign in