Investigating hyponatraemiaBMJ 2011; 342 doi: http://dx.doi.org/10.1136/bmj.d1118 (Published 07 March 2011) Cite this as: BMJ 2011;342:d1118
- Ammar Wakil, locum consultant, diabetes and endocrinology1,
- Jen Min Ng, clinical research fellow1,
- Stephen L Atkin, head, academic endocrinology, diabetes and metabolism1
- Correspondence to: A Wakil
- Accepted 15 November 2010
History, especially drug history, and focused examination of heart rate, blood pressure, venous filling, peripheral oedema, and cognitive function should identify possible causes, severity, and the fluid status in patients with hyponatraemia
Hyponatraemia usually has multiple causes with SIADH and drugs (especially thiazides) the commonest
The criteria to diagnose SIADH are hyponatraemia, urine osmolality >100 mOsm/kg and urinary sodium ≥30 mmol/L in the absence of hypovolaemia and hypervolaemia
A 70 year old woman with chronic obstructive pulmonary disease who smoked 30 cigarettes daily was admitted to the emergency department after a fall and a fracture of the left neck of femur. Her daughter stated that her mother had lately seemed confused and unsteady, and that she had lost weight. She was using a β agonist inhaler and taking no other drugs. On examination, she looked emaciated, had nicotine stained fingers, and was disorientated in time. Blood pressure was 140/85 mm Hg with no postural drop. Chest examination found scattered wheeze; no cardiac, abdominal, or other neurological abnormalities were found. Results of biochemistry were sodium 122 mmol/L (normal range 136-146 mmol/L), potassium 4.8 mmol/L (3.5-5.3 mmol/L), urea 1.7 mmol/L (2.1-7.6 mmol/L), and creatinine 55 mmol/L (51-107 mmol/L). Liver function tests, plasma glucose concentration, and lipids were normal. Computed tomography of the brain was normal.
What is the next investigation?
Hyponatraemia (a serum sodium concentration <136 mmol/L) is found in up to 42% of inpatients.1 Hyponatraemia may be asymptomatic if it is mild to moderate (>125 mmol/L) and chronic (>48 hours). Symptoms and signs due to brain oedema occur in severe (≤125 mmol/L) or acutely developing (<48 hours) hyponatraemia.2 As hyponatraemia advances, clinical features are headache, malaise, nausea, vomiting, cramps, lethargy, disorientation, unsteadiness and seizure, respiratory arrest, and death.3 Additionally, patients may present with the symptoms and signs of the underlying cause. In a study on the aetiological factors of severe hyponatraemia (≤125 mmol/L), 79 out of 105 inpatients had multiple causes, including heart failure in 27, dehydration in 20, thiazide drugs in 29, liver disease in 21, pneumonia in 15, central nervous system lesions in 13, and other drugs in 46. Causes of syndrome of inappropriate antidiuretic hormone (SIADH), also known as syndrome of inappropriate antidiuresis (SIAD), were present in 65 of the 105 patients.2 4 The box shows possible underlying causes.
Causes of hyponatraemia
Salt wasting nephropathy
Third space loss:
Small bowel obstruction
Syndrome of inappropriate antidiuretic hormone (SIADH)
Selective serotonin reuptake inhibitors
Non-steroidal anti-inflammatory drugs
Small cell lung cancer
Central nervous system:
Congestive cardiac failure
Liver cirrhosis with ascites and peripheral oedema Nephrotic syndrome
The first step in establishing the cause of hyponatraemia is a careful history focusing on the predisposing causes (see box), especially drug history and background history of heart failure, renal failure, liver disease, respiratory symptoms, and fluid loss.5 Clinical examination should be focused on fluid status, including blood pressure, postural deficit, heart rate, peripheral oedema, and central venous filling, as well as chest and heart examination. This clinical assessment should identify potential causes, establish the severity of hyponatraemia, and determine if the patient is hypovolaemic, euvolaemic, or hypervolaemic.
Our patient’s history provides clues to the extent of hyponatraemia. Disorientation and unsteadiness are features of severe hyponatraemia; in a smoker, emaciation and weight could be caused by hyponatraemia. The absence of signs of hypovolaemia (normal blood pressure with no postural deficit) and hypervolaemia (lack of peripheral oedema and normal venous pressure) indicates that she has euvolaemic hyponatraemia.
Normal results of liver function tests, lipids, and glucose concentration exclude rare causes of artifactual pseudohyponatraemia (hyperproteinaemia and hyperlipidaemia) or hyperosmolar hyponatraemia, where water moves from the intracellular to the extracellular compartment (in severe hyperglycaemia).3 Therefore our patient has true hyponatraemia, which can be classified as euvolaemic hyponatraemia (figure ⇓). The differential diagnosis of euvolaemic hyponatraemia includes SIADH, adrenocortical insufficiency, and debatably severe hypothyroidism, but by far the most common cause is SIADH.4 Since there are no clinical features of glucocorticoid deficiency (for example, history of vomiting and low blood pressure on examination) and hypothyroidism (for example, features of myxoedema such as weight gain and nonpitting oedema), a short tetracosactide (Synacthen) test and thyroid tests are not needed and our patient is likely to have SIADH.
A diagnosis by exclusion, SIADH needs to be confirmed by results of paired serum and urine samples: serum hyposmolality must be <275 mOsm/kg (normal range: 275-295 mOsm/kg), and urine osmolality >100 mOsm/kg and sodium ≥30 mmol/L, in the absence of hypovolaemia, hypervolaemia, adrenal or thyroid dysfunction and use of diuretics.2 6 Paired serum and spot urine samples need to be sent for osmolality and sodium to confirm both hyponatraemia and SIADH. Serum osmolality is not necessary when there is an obvious contributory cause. It can confirm true hyponatraemia (<275 mOsmol/kg) and rules out the rarer hyperosmolar hyponatraemia and pseudohyponatraemia (serum osmolality ≥275 mmol/L).3
Urine osmolality (normal range 300-900 mOsm/kg) is needed to confirm SIADH but it also helps in differentiating it from two other conditions. By definition SIADH is an incomplete suppression of antidiuretic hormone (urine osmolality >100 mOsm/kg); a spot urinary osmolality <100 mOsm/kg indicates appropriate complete suppression. Complete suppression of antidiuretic hormone is seen in psychogenic polydipsia (history of mental illness) and malnutrition (history of heavy alcohol consumption).7
Urinary sodium concentration is helpful when the cause of hyponatraemia is not apparent from the history and examination or when SIADH is suspected. In euvolaemic hyponatraemia (including SIADH), the urinary sodium is ≥30 mmol/L (normal values varies with diet8).6 Hypervolaemic hyponatraemia should be apparent clinically; because of the reduced effective circulating volume, the kidney concentrates the urine (>100 mOsm/kg) and conserves sodium (<30 mmol/L; but it can be higher when the patient is taking diuretics).6 The clues to hypovolaemia in the history (see box) include obvious fluid loss (through diuretics, for example) or third space fluid loss, when fluid with high sodium content is sequestered in a body space (as in burns). The urinary sodium concentration in all hypovolaemic hyponatraemia is <30 mmol/L except when the kidney is the site of the loss, for example with diuretic use, salt losing nephropathy, or mineralocorticoid deficiency.9
When the fluid status is difficult to determine clinically, low serum concentrations of urea and uric acid indicates SIADH, and a raised concentration of urea is more likely to reflect hypovolaemia.7
That this patient had SIADH is evidenced by her serum osmolality of 235 mOsm/kg, urinary osmolality of 350 mOsm/kg, and urinary sodium concentration of 95 mmol/L. Her intake of fluids was restricted and she was given tolvaptan 15 mg once daily, which gradually raised the serum sodium concentration. Chest imaging showed a lesion in the left lung, and a biopsy confirmed small cell carcinoma of the lung.
Cite this as: BMJ 2011;342:d1118
This series of occasional articles provides an update on the best use of key diagnostic tests in the initial investigation of common or important clinical presentations. The series advisers are Steve Atkin, professor, head of department of academic endocrinology, diabetes, and metabolism, Hull York Medical School; and Eric Kilpatrick, honorary professor, department of clinical biochemistry, Hull Royal Infirmary, Hull York Medical School. To suggest a topic for this series, please email us at email@example.com.
Contributors: SLA had the idea for the article; AW performed the literature search and wrote the article. JMN and SLA edited and contributed to the writing. SLA is guarantor.
Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and all authors declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned, externally peer reviewed.
Patient consent not required (patient is hypothetical).