11/14/24, 10\:42 AM Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Syndrome of Inappropriate Antidiuretic Hormone Secretion

(SIADH)

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Succinct notes to superpower your revision
SIADH\: excessive secretion of ADH, causing water retention and dilution of blood, decreasing sodium concentration.
Normal physiology\: ADH produced by hypothalamus, transported to posterior pituitary, released to kidneys, promotes
water reabsorption, reducing serum osmolality.
SIADH physiology\: lack of negative feedback; continual ADH production, leading to low serum sodium, high urinary
sodium.
Causes\: primary brain injury, malignancy (e.g. small-cell lung cancer), drugs (e.g. carbamazepine), infections,
hypothyroidism.
Symptoms\: mild hyponatraemia (nausea, headache); moderate (muscle cramps, confusion); severe (seizures, coma).
Clinical signs\: decreased consciousness, cognitive impairment, seizures, hypervolaemia (pulmonary oedema, peripheral
oedema).
Investigations\: low serum sodium, low plasma osmolality, high urine osmolality and sodium, TFTs, serum cortisol, chest X-
ray/CT.
Diagnosis\: hyponatraemia, low plasma osmolality, high urine osmolality, urine [Na+] >40 mmol/L, euvolaemia, normal
thyroid/adrenal function.
Management\: treat underlying cause,
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A comprehensive topic overview

What is SIADH?

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterised by excessive secretion of
antidiuretic hormone (ADH) from the posterior pituitary gland or another source.
ADH controls water reabsorption via its e
solutes). By increasing water retention, ADH assists in the dilution of the blood, decreasing the concentration of solutes
such as sodium.
You may also be interested in our comprehensive guide to hyponatraemia.

Physiology

Normal physiology

1. ADH (also known as vasopressin) is produced by the hypothalamus in response to increased serum osmolality.
2. ADH is transported from the hypothalamus to the posterior pituitary gland.
3. ADH is released into the circulatory system via the posterior pituitary gland.
4. ADH then travels to the kidneys, where it binds to ADH receptors on the distal convoluted tubules.
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5. The binding of ADH to these receptors causes aquaporin-2 channels to move from the cytoplasm, into the apical
membrane of the tubules. These aquaporin-2 channels allow water to be reabsorbed out of the collecting ducts and back
into the bloodstream. This results in both a decrease in volume and an increase in osmolality (concentration) of the urine
excreted.
6. The extra water that has been reabsorbed re-enters the circulatory system, reducing the serum osmolality.
7. This reduction in serum osmolality is detected by the hypothalamus and results in decreased production of ADH.
An illustration of how serum osmolality is regulated in healthy individuals.

Deranged physiology in SIADH

The critical di
mechanism. This results in continual ADH production, independent of serum osmolality.
Ultimately, this leads to abnormally low serum sodium levels and relatively high urinary sodium levels, giving rise to the
characteristic clinical features associated with SIADH.

What causes SIADH?

There are lots of potential causes of SIADH, including\:
Primary brain injury (e.g. meningitis, subarachnoid haemorrhage)
Malignancy (e.g. small-cell lung cancer)
Drugs (e.g. carbamazepine, SSRIs, amitriptyline)
Infectious (e.g. atypical pneumonia, cerebral abscess)
Hypothyroidism
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Causes of SIADH

Clinical features

History

The symptoms of SIADH vary depending upon both the severity of the hyponatraemia and the rate at which it develops\:
Mild hyponatraemia\: nausea, vomiting, headache, anorexia and lethargy.
Moderate hyponatraemia\: muscle cramps, weakness, confusion and ataxia.
Severe hyponatraemia\: drowsiness, seizures and coma.
Mild hyponatraemia may cause signi
patients may have very low serum sodium concentrations and yet be asymptomatic.
This is thought to be due to a compensatory process known as cerebral adaptation, in which brain cells adapt their
metabolism to cope with abnormal sodium levels. Cerebral adaptation can only occur if the change in sodium
concentration is gradual, explaining the more severe symptoms associated with acute hyponatraemia and the potentially
less severe symptoms associated with chronic hyponatraemia.
1

Clinical examination

The clinical signs of SIADH can also vary signi
Clinical signs of SIADH can include\:
2
Decreased level of consciousness
Cognitive impairment\: short-term memory loss, disorientation and confusion
Focal or generalised seizures
Brain stem herniation (severe acute hyponatraemia) results in coma and respiratory arrest
Hypervolaemia\: pulmonary oedema, peripheral oedema, raised jugular venous pressure and ascites
Fluid status assessment
A is vital in any patient with hyponatraemia\:
Patients with SIADH are typically euvolemic or hypervolaemic (i.e. not dehydrated)
If dehydration is present, it may suggest an alternative cause for the hyponatraemia (e.g. diuretic-related renal failure)
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Investigations

Laboratory investigations

Relevant laboratory investigations include\:
Urea & electrolytes\: serum sodium is low in SIADH (\<130 mmol/L).
Plasma osmolality\: reduced in SIADH (due to low serum sodium).
Thyroid function tests (TFTs)\: hypothyroidism is a potential cause of SIADH.
Serum cortisol\: should be checked to rule out Addison's disease as a cause of hyponatraemia (cortisol is reduced in
Addison's disease).

Urine tests

Urine osmolality\: in healthy individuals, if serum osmolality is low, urine osmolality should also be low, as the kidneys
should be working hard to retain solute. In SIADH, excess ADH results in water retention but not solute retention. As a result,
concentrated urine (which is relatively high in sodium) is produced despite low serum sodium.
Urine sodium\: raised in SIADH despite low serum sodium concentration.

Imaging

Chest X-ray and/or CT-chest\: used to rule out causes of SIADH (e.g. small cell lung cancer, atypical pneumonia).

Diagnosis

The following features must be present for a diagnosis of SIADH to be established\: ³
Hyponatraemia
Low plasma osmolality
Inappropriately elevated urine osmolality (i.e. greater than plasma osmolality)
Urine [Na+] >40 mmol/L despite normal salt intake
Euvolaemia
Normal thyroid and adrenal function

Management

Management of SIADH varies depending on the underlying cause. De
underlying cause of SIADH.

Fluid restriction

Fluid restriction is a common management strategy used to increase serum sodium concentrations, at least temporarily,
whilst the underlying cause is sought and treated. This strategy greatly depends on patients cooperating with the
treatment plan, as
The management algorithm below provides an overview of the current guidelines on the management of SIADH.
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Acromegaly
Addison's Disease (Primary Adrenal Insu
Cushing's Syndrome
Diabetes Insipidus
Growth Hormone De
Copyright © 2015 The Authors European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting
European Society for Clinical Investigation Journal Foundation.

Test yourself

References

Craig S; Hyponatremia in Emergency Medicine, Medscape, Published Apr 2010.
What is SIADH?
Robert D. Zenenberg, Do, et. al (2010-04-27).
"Hyponatremia\: Evaluation and Management"
. Hospital Practice. 38 (1)\: 89–96
Physiology
Grant P, Ayuk J, Bouloux PM, et al; The diagnosis and management of inpatient hyponatraemia and SIADH. Eur J Clin Invest.
2015 Aug45(8)\:888-94. doi\: 10.1111/eci.12465. Epub 2015 Jun 28. Available from\: [LINK]
What causes SIADH?
Clinical features
Investigations
Diagnosis
Management
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