21st May 2025

Hyponatraemia and SIADH

Hyponatraemia

Hyponatraemia is thought to occur in 15-28% of patients admitted to hospital, and approximately 25% of elderly patients with hyponatremia may have SIADH (Syndrome of inappropriate secretion of antidiuretic hormone) of which the most common causes are respiratory disease and malignancy. 

NICE guidelines state:

“Hyponatraemia is defined as a serum sodium concentration of less than 135 mmol/L.”

Normal range: serum sodium concentration of 135-145 mmol/L

Mild: 130-135 mmol/L (serum concentration of sodium)

Moderate: 125-129 mmol/L (serum concentration of sodium)

Severe: Less than 125 mmol/L (serum concentration of sodium)”

Causes of Hyponatraemia

Table 1: Causes of Hyponatraemia

Pulmonary embolism is also a common cause of hyponatraemia within hospital in-patients.

Drug-related causes of hyponatraemia 

Table 2: Drug-related causes of hyponatraemia

Classification of Hyponatraemia

Acute vs Chronic 

It is important to define whether a hyponatraemia is acute i.e. a duration of less than 48 hours or chronic i.e. a duration greater than 48 hours. See below sections for further information on the management. 

Fluid status 

Hyponatraemia is classified according to 3 sub-groups:

1. Hypovolaemia – volume depletion i.e. dehydration
2. Euvolaemia – a normal volume status 
3. Hypervolaemia – volume overload  

Therefore when defining a hyponatraemia we should consider:

1. Is the hyponatraemia mild, moderate or severe?
2. Is this acute or chronic? i.e. less than or greater than 48 hours in duration
3. What is the patient’s fluid status? i.e. hypovolaemic/ euvolaemic/ hypervolaemic
4. Is the patient symptomatic?

Being able to answer these 4 questions will allow us to determine an appropriate management plan for each patient.

Presentation

It is important to note that patients with long-term, chronic hyponatraemia are often asymptomatic. However, the symptoms to look out for, especially in patients with acute changes to serum sodium levels include: 

• nausea
• vomiting
• confusion
• muscle cramping
• cognitive impairment
• gait disturbances
• depression
• tremors 
• hallucinations
• respiratory depression
• coma

Management

Management will vary based on the duration of hyponatraemia, patient’s volume status and whether or not the patient is symptomatic. 

Acute onset (<48 hours) + Asymptomatic/ mild symptoms

1. Stop potential offending medications

2. Fluid intake should depend on the patient’s fluid status:

• Hypovolaemic: replace losses with 0.9% saline to restore the extracellular volume

• Euvolaemic: ensure all fluids given are essential and that any non-essential fluids are stopped

• Hypervolaemic: Fluid restrict these patients

3. Investigate for a cause and treat accordingly

Acute onset (<48 hours) + Moderate/ severe symptoms

1. Administer hypertonic saline

GAIN guidelines state that 200mls of 2.7% saline should be administered over 30 minutes. If this is required, sodium levels should be checked two hourly with an aim to increase levels by 1-2 mmol/L every hour until the patient’s symptoms resolve. 

2. Fluids restrict these patients to 1-1.5 L daily and investigate for a cause including infection, stress, medication or other hypotonic fluids.

3. Monitor sodium daily.

It is often useful to discuss these patients with a consultant biochemist who will often be able to provide additional advice and support.

Chronic onset (>48 hours/unknown onset) without severe symptoms

General management

• Review medications and IV fluid prescriptions – stop any non-essential ones that may be contributing
• Investigations (bloods, paired serum and urine sodium and osmolalities)
  • Consider further investigation for underlying cause if SIADH diagnosed (see below section) 
• If mild hyponatraemia, treat the underlying cause
• If moderate/severe hyponatraemia, check serum levels daily until stable, and increase serum sodium by no more than 10mmol/L in the first 24 hours, and no more than 8mmol/L/24 hours thereafter
• If patient is fluid overloaded or has SIADH, treat with fluid restriction and consider diuresis
• If hypovolaemic, treat with IV crystalloid such as 0.9% sodium chloride

Chronic onset with severe symptoms

Treat as for acute onset with severe symptoms. 

If patients are haemodynamically unstable, resuscitation should be prioritised over concerns about rapid correction of serum sodium levels, and adequate resuscitation fluid should be given.

Syndrome of Inappropriate Anti-Diuretic Hormone Secretion (SIADH) 

SIADH is the most common cause of hyponatraemia in hospitalised patients. It is a condition in which the body is unable to suppress anti-diuretic hormone (ADH) secretion from the posterior pituitary gland causing water retention and eventually hyponatraemia.

Aetiology

The causes of SIADH are various. A useful mnemonic for remembering these causes is, “SIADH” 

Surgery – pituitary/ neurosurgery

Intracranial – head injury, intracranial infections, stroke, pituitary apoplexy, hypopituitarism

Alveolar causes – small cell lung cancer

Drugs – thiazide diuretics, cyclophosphamide, TCAs, carbamazepine, SSRIs, opioids

Hormonal – low cortisol, hypothyroidism, Addison’s disease 

Other causes include HIV infection, Guillain-Barre syndrome, multiple sclerosis, tuberculosis, pneumonia (particularly if caused by legionella or mycoplasma)

Diagnosis

The criteria for diagnosing SIADH include:

• Clinically euvolaemic
• Serum osmolality <275 mOsmol/kg 
• Urine Sodium >15 mmol/L
• Significantly raised urine osmolality >100 mOsmol/kg
• No evidence of other causes including adrenal, thyroid, pituitary or renal disease

Note: There is often (but not always) evidence of low serum uric acid/ urea

It is important to interpret these values with caution if a patient is on diuretic therapy.

The cause of hyponatraemia is often multifactorial and therefore it is important to thoroughly assess a patient and to rule out other potential causes.

Management

If the patient meets the criteria for SIADH, then they should be managed as follows:

1. Fluid restriction
2. Investigate for a cause – if this is not obvious a CT chest, abdomen, pelvis and MRI head should be organised to rule out a possible malignancy
3. Tolvaptan should be considered

Complications of treatment of hyponatraemia and SIADH

Central pontine myelinolysis 

Rapidly correcting hyponatraemia can cause demyelination of the central pons and can cause serious neurological symptoms including locked-in syndrome and even death. It is therefore vital that sodium correction does not exceed more than 12 mmol in 24 hours.

References

Xu Zhang, Xiao-Ying Li. Prevalence of hyponatremia among older inpatients in a general hospital. Eur Geriatr Med [Internet]. 2020 [cited 2023 Feb 2]; 11(4):685–92. Available from: https://pubmed.ncbi.nlm.nih.gov/32372184/

National Institute for Health and Care Excellence. Hyponatraemia [Internet]. Nice Guidelines. 2020 [cited 2023 Feb 2]. Available from: National Institute for Health and Care Excellence

Pillai B, Unnikrishnan A, Pavithran P. Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder. Indian J Endocrinol Metab. 2011; 15(7):208. 

Epomedicine. Hyponatremia : SIADH vs Cerebral Salt Wasting Syndrome [Internet]. 2019 [cited 2023 Feb 2]. Available from: https://epomedicine.com/medical-students/hyponatremia-siadh-csws/

GP Notebook. Drugs causing SIADH [Internet]. 2022 [cited 2023 Feb 2]. Available from: https://gpnotebook.com/simplepage.cfm?id=2020278340

Yasir M, Mechanic O. Syndrome of Inappropriate Antidiuretic Hormone Secretion [Internet]. StatPearls Publishing; 2022 [cited 2023 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507777/#:~:text=Nonspecific%20symptoms%20like%20nausea%2C%20vomiting,the%20history%20and%20physical%20examination.

Gain Guidelines. Hyponatraemia in adults (on or after 16th birthday) [Internet]. GAIN guidelines. 2010 [cited 2023 Feb 2]. Available from: https://www.rqia.org.uk/RQIA/files/9f/9f29d996-722a-4aff-8937-59b937602070.pdf

Lambeck J, Hieber M, Dreßing A, Niesen WD. Central Pontine Myelinosis and Osmotic Demyelination Syndrome. Dtsch Arztebl Int. 2019 Sep 2; 

Rondon H, Badireddy M. Hyponatraemia [Internet]. StatPearls Publishing; 2022 [cited 2023 Feb 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470386/

Liamis G, Filippatos TD, Elisaf MS. Thiazide-associated hyponatremia in the elderly: what the clinician needs to know. J Geriatr Cardiol. 2016 Feb; 13(2):175–82. 

Wang Wenxian, Song Zhengbo, Zhang Yiping. Hyponatremia in small cell lung cancer is associated with a poorer prognosis. Transl Cancer Res [Internet]. 2013 Feb 1 [cited 2023 Feb 2];5(1). Available from: https://tcr.amegroups.com/article/view/6481/html#:~:text=Hyponatremia%20with%20SCLC%20patients%20occurs,abnormalities%20of%20clinical%20laboratory%20tests

Hannon MJ, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol. 2010 Jun; 162(Suppl1):S5–12. 

Lu D, Cheng H, Cheng Y, Hsu P, Huang W, Guo C, et al. Hyponatremia and Worsening Sodium Levels Are Associated With Long‐Term Outcome in Patients Hospitalized for Acute Heart Failure. J Am Heart Assoc. 2016 Mar 9;5(3). 

Traub SJ. The ‘Ecstasy’ Hangover: Hyponatremia Due to 3,4-Methylenedioxymethamphetamine. J Urban Health. 2002 Dec 1;79(4):549–55. 

Ammar Wakil and Atkin, S.L. (2010). Serum sodium disorders: safe management. Clinical Medicine, [online] 10(1), pp.79–82. doi:https://doi.org/10.7861/clinmedicine.10-1-79.

Schrz, N., Labarère, J., Méan, M., Ibrahim, S.A., Fine, M.J. and Aujesky, D. (2010). Prognostic Importance of Hyponatremia in Patients with Acute Pulmonary Embolism. American Journal of Respiratory and Critical Care Medicine, 182(9), pp.1178–1183. doi:https://doi.org/10.1164/rccm.201003-0481oc.