SIADH
Last updated 18th March 2019 - Tom Heaton
Syndrome of inappropriate antidiuretic hormone (SIADH) is an important cause of hyponatraemia.
This is a good introductory video from the guys at Osmosis: https://www.youtube.com/watch?v=0NHT8ERUBo0
This is also a good video from Armando Hasudungan: https://www.youtube.com/watch?v=qlur2m72Pmc
This is a good introductory video from the guys at Osmosis: https://www.youtube.com/watch?v=0NHT8ERUBo0
This is also a good video from Armando Hasudungan: https://www.youtube.com/watch?v=qlur2m72Pmc
Pathophysiology
ADH plays a key role in regulating the balance of water in the body.
A summary of the normal physiology is worth knowing and is available here: http://www.medicalphysiology.co.uk/fluid--electrolyte-overview.html
It is released from the posterior pituitary in response to an increase in serum osmolarity and causes increased uptake from the collecting ducts of the nephron by increasing the expression of aquaporin type 2.
This leads to an increase in water reabsorption and a drop in serum osmolarity, hence forming a negative feedback loop.
SIADH results from an increased release of ADH, beyond the normal homeostasis requirements, and a subsequently an increased action in reabsorbing water.
The result is excess water retention and a dilutional effect on the body compartments
Now there is some ‘compensation’ through the other mechanisms of sodium and fluid homeostasis.
The increased volume results in a decreased activity of the renin-angiotensin-aldosterone system (RAAS), both renally and through the natriuretic peptides.
The reduction in aldosterone results in reduced renal sodium reabsorption and some parallel water loss in the urine.
This is an important pathological feature of SIADH, as sodium loss is ongoing despite hyponatraemia.
A steady state arises that is euvolaemic.
A summary of the normal physiology is worth knowing and is available here: http://www.medicalphysiology.co.uk/fluid--electrolyte-overview.html
It is released from the posterior pituitary in response to an increase in serum osmolarity and causes increased uptake from the collecting ducts of the nephron by increasing the expression of aquaporin type 2.
This leads to an increase in water reabsorption and a drop in serum osmolarity, hence forming a negative feedback loop.
SIADH results from an increased release of ADH, beyond the normal homeostasis requirements, and a subsequently an increased action in reabsorbing water.
The result is excess water retention and a dilutional effect on the body compartments
Now there is some ‘compensation’ through the other mechanisms of sodium and fluid homeostasis.
The increased volume results in a decreased activity of the renin-angiotensin-aldosterone system (RAAS), both renally and through the natriuretic peptides.
The reduction in aldosterone results in reduced renal sodium reabsorption and some parallel water loss in the urine.
This is an important pathological feature of SIADH, as sodium loss is ongoing despite hyponatraemia.
A steady state arises that is euvolaemic.
Aetiology
There are a large number of causes of SIADH.
It is worth remembering them via a systematic approach - MAD CHOP is a good acronym
It is worth remembering them via a systematic approach - MAD CHOP is a good acronym
- Major Surgery
- ADH production by tumours (Ectopic)
- Small cell lung cancer
- Leukaemia
- Lymphomas
- Thymoma
- Adenocarcinoma of pancreas/duodenum
- Small cell lung cancer
- Drugs
- Antidepressants - SSRIs, MAOIs, tricyclics
- Neuroleptics
- Anticonvulsants
- Anaesthetic agents - barbiturates, volatile anaesthetic agents
- Opioids
- ADH analogues - vasopressin, DDAVP
- Chemotherapy agents - vinca alkaloids, methotrexate, cyclophosphamide
- Others - NSAIDs, amiodarone, ciprofloxacin, PPIs, MDMA
- Antidepressants - SSRIs, MAOIs, tricyclics
- CNS
- Trauma
- Infections
- Tumours
- Subarachnoid haemorrhage
- Trauma
- Hormonal
- Hypothyroidism
- Adrenal insufficiency
- Hypothyroidism
- Other
- Guillain-Barre syndrome
- Hereditary
- HIV
- Giant cell arteritis
- Porphyria
- Guillain-Barre syndrome
- Pulmonary
- Pneumonia
- Lung abscess
- Pneumonia
Presentation
A significant component of the symptomatology arises from the hyponatraemia (see the notes here).
As such, the presentation will be similar, including being impacted upon by the acuity of the sodium drop.
However, as you can see, a number of the presentations will be highly symptomatic in their own right, and this overlap may complicate the presentation.
As such, the presentation will be similar, including being impacted upon by the acuity of the sodium drop.
However, as you can see, a number of the presentations will be highly symptomatic in their own right, and this overlap may complicate the presentation.
Investigation
This will be similar to the investigation of hyponatraemia.
Investigations may include:
Bloods
The key results will be:
In cases where a more specific cause is suspected, investigations may be further guided towards this e.g. head imaging.
Investigations may include:
Bloods
- FBC
- U&Es
- Serum osmolarity - measure vs calculated
- TFTs
- Urinary electrolytes
- Urine osmolarity
The key results will be:
- Hyponatraemia
- Low osmolarity
- Higher than appropriate urinary sodium - >20 mmol/L
- Higher than appropriate urine osmolarity
In cases where a more specific cause is suspected, investigations may be further guided towards this e.g. head imaging.
Diagnostic Criteria
Based on this assessment, the criteria to make a diagnosis of SIADH are:
It is also important that there has been no recent diuretic use.
This would alter the results of urine analysis.
- Hypotonic hyponatremia
- Urine osmolarity > plasma osmolality
- Urinary sodium > 20 mmol/L
- Normal renal, cardiac, hepatic, thyroid, pituitary and adrenal function
- Euvolaemia
- Correction by water restriction
It is also important that there has been no recent diuretic use.
This would alter the results of urine analysis.
Management
The principles of management overlap with that of hyponatraemia to some degree, but can be summarised as:
Treat Hyponatraemia
In cases where there is a severe acute drop in the plasma sodium level, symptoms will likely develop due to cerebral oedema.
This needs urgent treatment, as noted in the hyponatraemia notes, and will usually involve hypertonic saline.
If the change is more chronic, this correction should be done more slowly.
Treat Underlying Cause
This is clearly important to allow reversal of the excess ADH.
In some cases this may be easier that others, but routine steps can be taken e.g drug review.
Fluid Restriction
A fluid restriction, usually 500ml-1000ml is usually instigated to aid correction.
With reduced ongoing water intake, the level of ADH starts to become more appropriate to the patient’s hydration state.
As such, this starts to result in correction of the electrolyte disturbance.
Demeclocycline
This is a treatment for more chronic SIADH.
It blocks the action of ADH at the nephron level (inducing nephrogenic diabetes insipidus) and thereby reducing fluid uptake in this way.
- Treat severe acute hyponatraemia urgently
- Treat the underlying cause
- Restrict fluid intake
- Demeclocycline (chronic ADH)
Treat Hyponatraemia
In cases where there is a severe acute drop in the plasma sodium level, symptoms will likely develop due to cerebral oedema.
This needs urgent treatment, as noted in the hyponatraemia notes, and will usually involve hypertonic saline.
If the change is more chronic, this correction should be done more slowly.
Treat Underlying Cause
This is clearly important to allow reversal of the excess ADH.
In some cases this may be easier that others, but routine steps can be taken e.g drug review.
Fluid Restriction
A fluid restriction, usually 500ml-1000ml is usually instigated to aid correction.
With reduced ongoing water intake, the level of ADH starts to become more appropriate to the patient’s hydration state.
As such, this starts to result in correction of the electrolyte disturbance.
Demeclocycline
This is a treatment for more chronic SIADH.
It blocks the action of ADH at the nephron level (inducing nephrogenic diabetes insipidus) and thereby reducing fluid uptake in this way.
Links & References
- Osmosis. Syndrome of inappropriate antidiuretic hormone (SIADH). Youtube. 2015. https://www.youtube.com/watch?v=0NHT8ERUBo0
- Hasudungan, A. Syndrome of inappropriate antidiuretic hormone -SIADH (causes, pathophysiology, hyponaturemia, treatment). Youtube. 2018. https://www.youtube.com/watch?v=qlur2m72Pmc
- Heaton, T. Fluid & Electrolyte Overview. MedicalPhysiology.co.uk. 2019. http://www.medicalphysiology.co.uk/fluid--electrolyte-overview.html
- Nickson, C. SIADH - Syndrome of inappropriate ADH secretion. LITFL. 2015. https://lifeinthefastlane.com/ccc/siadh-syndrome-of-inappropriate-adh-secretion/
- Hirst, C. et al. The adult patient with hyponatraemia. 2015. CEACCP. 15(5):248-252. https://academic.oup.com/bjaed/article/15/5/248/240571
- Potter, L. Black, Z. SIADH. Geeky Medics. https://geekymedics.com/syndrome-of-inappropriate-antidiuretic-hormone-secretion-siadh/
- Newson, L. Hyponatraemia. Patient.info. 2016. https://patient.info/doctor/hyponatraemia-pro
