QuestionSBA
QuestionChoice
Patients with SIADH are usually euvolaemic or hypervolaemic. Clinical dehydration suggests other causes for hyponatraemia such as secondary to diuretics or acute kidney injury
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Clinical dehydration
QuestionChoice
A low serum cortisol and hyponatraemia suggests Addison's disease
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Low serum cortisol
QuestionChoice
In SIADH there are high levels of antidiuretic hormone (ADH) in the blood. This leads to increased retention of water, but not sodium. There is therefore low levels of salt in the blood and therefore low plasma osmolality. Urine produced is more concentrated (as less water is excreted) and has more sodium, leading to a high urine osmolality and high urine sodium level. Urine osmolality greater than plasma osmolality can only be induced by inappropriately high levels of ADH in the bloodstream
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Urine osmolality greater than plasma osmolality
QuestionChoice
Hypothyroidism is one of the potential causes for SIADH and so TFTs should be checked when investigating for SIADH. However, whether TFTs are normal or abnormal has no bearing on the diagnosis of SIADH
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Normal thyroid function tests (TFTs)
QuestionChoice
In SIADH, due to increased water retention secondary to the high levels of ADH, concentrated urine with high sodium levels is produced (high urine osmolality). As excessive sodium is being excreted and water is excessively retained, plasma sodium is low and plasma osmolality is high. Therefore, by definition, urine osmolality will be greater than plasma osmolality
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Plasma osmolality greater than urine osmolality
QuestionComment
how is this diagnostic if urine osmolarity is higher than plasma in healthy patients? 
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SIADH is inappropriate activation of V2 (aquaporin) receptor so more water is reabsorbed back into the capillaries lowering urine water volume. Lower urine water volume means that theres more solutes in the urine so the osmolality would be higher. Osmolality is the measure of how many substances are dissolved in 1kg of water.
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Jaundice Myopathy
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# Summary

Syndrome of Inappropriate ADH secretion (SIADH) refers to excessive antidiuretic hormone (ADH) release, causing water to be retained resulting in a euvolemic hyponatraemia. There are a wide range of causes including medications, malignancy, central nervous system (CNS) disorders and infections. Patients may be asymptomatic and detected through an incidental finding of a low serum sodium, or may present with features of severe hyponatraemia (e.g. confusion, seizures) and/or the underlying cause of SIADH. Key investigations include U&Es for sodium, cortisol and thyroid function to rule out other causes of hyponatraemia and urinary sodium and osmolality (which will be greater than 30 mmol/L and 100 mOsm/kg respectively). First-line management is with fluid restriction to 500-1000 ml/day, as well as treating the underlying cause (e.g. stopping causative medications). Severe cases may require hypertonic saline, and resistant cases may be treated with tolvaptan (an vasopressin V2-receptor antagonist).

# Definition

Syndrome of Inappropriate ADH secretion (SIADH) is an important cause of hyponatraemia that occurs when there is inappropriate release of antidiuretic hormone (ADH) outside of normal homeostatic mechanisms, which leads to reduced urine output. The increase in total body water effectively dilutes serum sodium, leading to hyponatraemia. 

Normally, ADH (also referred to as vasopressin) is produced in the hypothalamus and released from the posterior pituitary when serum osmolality is high. It acts to normalise osmolality by acting on the distal convoluted tubules and collecting ducts of the kidney to stimulate increased water reabsorption. 

SIADH may involve excessive release of ADH from the pituitary gland or production of ADH by an abnormal non-pituitary source (e.g. a tumour).

# Aetiology

SIADH has a wide range of causes - these are some examples:

- Pulmonary causes:
	- Pneumonia
	- Chronic Obstructive Pulmonary Disease (COPD)
	- Tuberculosis (TB)
- Central Nervous System (CNS) disorders:
	- Meningitis
	- Stroke
	- Subarachnoid haemorrhage
	- Traumatic brain injury
	- Psychosis
- Malignancies:
	- Small cell lung cancer
	- Pancreatic cancer
	- Lymphoma
	- Mesothelioma
	- Thymoma
	- Nasopharyngeal cancer
- Medications:
	- Carbamazepine
	- Selective Serotonin Reuptake Inhibitors (SSRIs)
	- Opiates
	- Anti-psychotics
	- Cyclophosphamide
- Other: 
	- HIV
	- Surgery
	- Acute intermittent porphyria
	- Idiopathic

# Signs and Symptoms

SIADH presents with a euvolaemic hyponatraemia, and so patients may be asymptomatic or present with features of the underlying cause (e.g. pneumonia).

Signs and symptoms of hyponatraemia are more likely to develop in severe cases and where sodium has fallen rapidly:

- Lethargy
- Anorexia
- Headache
- Nausea and vomiting
- Muscle cramps
- Drowsiness
- Confusion
- Seizures

# Differential Diagnosis

See the Hyponatraemia chapter for a full list of differentials - other causes of a euvolaemic hyponatraemia include:

- **Beer potomania** is a cause of hyponatraemia in the context of alcohol excess combined with low solute intake due to a poor diet
- **Primary polydipsia** occurs when people drink excessive amounts of water, leading to polyuria with dilute urine (as opposed to the smaller volume of concentrated urine seen in SIADH)
- **Hypothyroidism** may cause hyponatraemia in severe cases; patients will usually have other symptoms such as fatigue, cold intolerance and constipation
- **Adrenal insufficiency** causes hyponatraemia with hyperkalaemia; other features include hypotension, abdominal pain and weakness
- **Exercise-induced hyponatraemia** occurs during or in the 24 hours following prolonged exercise (e.g. running a marathon), usually due to excess intake of hypotonic fluids
- **Hypotonic intravenous fluids** such as 5% dextrose or 0.45% saline may lead to iatrogenic hyponatraemia

# Investigations

**Bedside:**

- **Venous blood gas** to confirm hyponatraemia - if there is a significant discrepancy between the sodium on the gas and the U&Es, suspect pseudohyponatremia (see Hyponatraemia chapter for details) 
- **Urine osmolality** will be high (> 100 mOsm/kg)
- **Urine sodium** will be high (> 30 mmol/L)
- NB urine osmolality and sodium cannot be interpreted in patients taking diuretics and so these need to be stopped prior to investigations

**Blood tests:**

- **U&Es** to confirm hyponatraemia; urea will also likely be low due to dilution
- **Serum osmolality** will be low (< 280 mOsm/kg)
- **Thyroid function tests** to exclude hypothyroidism as a cause of hyponatraemia
- **9am serum cortisol** to exclude adrenal insufficiency as a cause of hyponatraemia

**Imaging:**

- **Chest X-ray** if there is no obvious cause of SIADH as an initial screen for malignancy and pulmonary disease (e.g. tuberculosis, pneumonia)
- **CT chest, abdomen and pelvis** and **MRI head** may be considered to exclude occult malignancy if there is no identified cause

# Management

**Conservative:**

- Identify and treat the underlying cause (e.g. stopping causative medications where possible)
- Patients with suspected SIADH in primary care should be referred to endocrinology to confirm the diagnosis and advise on treatment
- Closely monitor sodium levels and ensure these are corrected no faster than 8-10 mmol/L per 24 hours 
- Fluid restriction is the first-line management in most cases, usually to 500-1000 ml/day 

**Medical:**

- Severe hyponatraemia should be treated with hypertonic saline, usually in the intensive care setting
- In some cases (e.g. SIADH resistant to fluid restriction), tolvaptan may be considered - this is a vasopressin V2-receptor antagonist

# Complications

- **Cerebral oedema** may complicate severe and/or acute hyponatraemia and may be life-threatening - patients develop raised intracranial pressure with symptoms of vomiting, headache, seizures and coma
- **Central pontine myelinolysis** is a complication of rapid correction of hyponatraemia - patients may present with confusion, ataxia, spastic quadriparesis and pseudobulbar palsy with dysphagia and dysarthria
- Chronic hyponatraemia, especially in the elderly, increases the risk of **falls** as well as **cognitive impairment**

# NICE Guidelines

[NICE CKS - Hyponatraemia](https://cks.nice.org.uk/topics/hyponatraemia/)

# References

[Life in the Fast Lane - Hyponatraemia](https://litfl.com/hyponatraemia/)

[Life in the Fast Lane - SIADH](https://litfl.com/siadh-syndrome-of-inappropriate-adh-secretion/)

[Whittington Hospital Hyponatraemia Guideline](https://www.whittington.nhs.uk/document.ashx?id=6089)
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A 73-year-old man is being investigated for hyponatraemia (serum Na 129 mmol/L; normal range 135-145 mmol/L) which was found on routine blood tests.


Which of the following results would be diagnostic of syndrome of inappropriate antidiuretic hormone secretion (SIADH)?
a