SIADH Flashcards
SIADH
The syndrome of inappropriate ADH secretion (SIADH) is characterised by hyponatraemia secondary to the dilutional effects of excessive water retention.
Causes of SIADH
Causes of SIADH
Malignancy:
small cell lung cancer
also: pancreas, prostate
Neurological: stroke subarachnoid haemorrhage subdural haemorrhage meningitis/encephalitis/abscess
Infections:
tuberculosis
pneumonia
Drugs: sulfonylureas* SSRIs, tricyclics carbamazepine vincristine cyclophosphamide MDMA/Ecstasy *the BNF states this has been reported with glimepiride and glipizide.
Other causes
positive end-expiratory pressure (PEEP)
porphyrias
SIADH - Mx
Management
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
NB: The initial treatment option for SIADH is by fluid restriction which, under most circumstances, will correct the biochemical abnormalities in almost every case.
SIADH Diagnosis: Example Question
A 58-year-old patient who has a history of hypertension is operated on by the neurosurgeons for an intracranial haemorrhage.
Over the next few days his serum sodium level progressively declines and by the third day has fallen to 118 mmol/l despite fluid restriction to 1L per day. Urine osmolarity is 700 mOsmo/l and urinary sodium is raised at 80 mmol/l.
What is the most likely diagnosis?
Addisonian crisis > Secretion of inappropriate antidiuretic hormone Cranial diabetes insipidus Hypovolaemia Fluid overload
The hyponatraemia and hypotonic blood plasma, coupled with the raised urine osmolality and raised urinary sodium excretion indicates a diagnosis of syndrome of inappropriate ADH secretion. This is a condition that can occur after head trauma, a central nervous system infection and intracranial haemorrhage.
SIADH vs Cerebral Salt Wasting Syndrome : Example Question
A 72-year-old woman is recovering on the neurosurgical unit following a subdural haemorrhage. Four days earlier she underwent Burr hole surgery. You are asked to see her due to a persistently low sodium for the past three days. You note the following investigations:
Day 2 post-surgery
Serum Na+ 116 mmol/l
Day 3 post-surgery
Serum Na+ 117 mmol/l
Day 4 post-surgery
Serum Na+ 115 mmol/l
Urinary Na+ 25 mmol/l
Serum osmolality 280 mmol/l
Examination of the patient demonstrates dry mucous membranes and delayed capillary refill time.
What is the most likely diagnosis?
SIADH Diabetes insipidus > Cerebral salt wasting syndrome Renal tubular acidosis type IV Sheehan's syndrome
Diabetes insipidus is classically associated with hypernatraemia. Sheehan’s syndrome refers to the specific situation of pituitary necrosis following childbirth. The cardinal feature of renal tubular acidosis type IV is hyperkalaemia.
This leaves SIADH and cerebral salt wasting syndrome. The hydration status in this patient can be considered hypovolaemic making SIADH unlikely (typically euvolaemic). Additionally, this diagnosis should only be made in the absence of hypothyroidism and adrenal dysfunction.
Cerebral salt wasting syndrome can occur following neurosurgery. It occurs due to sodium wasting in the urine. Comparatively, it is treated with replacing fluid and sodium losses.
Causes of SIADH
The causes of SIADH are as follows
1. Tumours Small cell CA of the lung Prostate Thymus Pancreas Lymphoma
- Pulmonary Lesions
Pneumonia
Tuberculosis
Lung abscess
3. CNS Causes Meningitis Tumours Head injury Subdural haematoma Cerebral abscess SLE Vasculitis
- Metabolic Causes
Alcohol withdrawal
Porphyrias
5. Drugs Carbamazepine Chlorpropamide Cyclophosphamide Vincristine Phenothiazines
SIADH 2dry to Carbamazepine Treatment: Example Question
A 28-year-old male with a history of epilepsy, for which he is taking carbamazepine and has not had any seizures for the last two years, presents with irritability and nausea for the last 2 weeks. His girlfriend says that he is often confused and seems to be lost most of the time. He takes alcohol occasionally and smokes ten to twelve cigarettes per day.
On examination, he is irritable but conscious and alert. Clinical examination revealed eczema over the face, shins and extensor surfaces of the forearms and a tattoo on the right shoulder. There was no evidence of any peripheral oedema.
Lab reports were as follows:
Hb 150 g/l MCV 81 fl MCH 31 pg WBC 9 * 109/l Plt 250 * 109/l Urea 3.2 mmol/l Creatinine 75 µmol/l 9:00 am Cortisol 345 nmol/l (170 700 nmol/l) TSH 2.4 mU/l Total T4 102 nmol/l (68 174 nmol/l) Na+ 119 mmol/l K+ 4.2 mmol/l
Which of the following would be the most appropriate initial management option?
> Fluid restriction to 500 - 1000 ml daily Demeclocycline 600 - 1200 mg daily IV hypertonic saline Intranasal desmopressin twice daily Hydrochlorothiazide 12.5 mg daily
The diagnosis in the scenario described above is SIADH secondary to carbamazepine treatment. The findings of eczema are coincidental and have no bearing on the diagnosis. However, in the management the presence of skin lesions such as eczema may pose difficulty in opting for the use of demeclocycline which may cause photosensitive rashes.
The initial treatment option for SIADH is by fluid restriction which, under most circumstances, will correct the biochemical abnormalities in almost every case.
Demeclocycline is indicated if fluid restriction is poorly tolerated or ineffective.
Hypertonic saline is indicated only when the syndrome is very severe, acute and symptomatic.
Intranasal desmopressin is used for the management of diabetes insipidus, and thiazide diuretics are only rarely used as alternative agents in diabetes insipidus.
Correction of Hyponatraemia - Cx:
Hyponatraemia: correction
Central pontine myelinolysis
demyelination syndrome caused by rapid correction of chronic hyponatraemia
may lead to quadriparesis and bulbar palsy
diagnosis: MRI brain
SIADH - Diagnosis: Example Question
A 70-year-old man with a history of smoking 15 cigarettes/day presents with drowsiness, weight loss and a persistent cough. His investigations show:
Na+ 115 mmol/l (135-145 mmol/l)
K+ 5.1 mmol/l (3.5 - 5.0 mmol/l)
Urea 3 mmol/l (2.0-7 mmol/l)
Creatinine 74 µmol/l (55-120 µmol/l)
Plasma osmolality
270 mOsm/kg (285-295 mOsm/kg)
Urine osmolality 1210 (500 - 800 mOsm/kg)
What is the most likely diagnosis?
> Small cell lung cancer Hypothyroidism Encephalitis Congestive cardiac failure Squamous cell carcinoma
Hyponatraemia, reduced plasma osmolality and increased urine osmolality are suggestive of syndrome of inappropriate ADH secretion (SIADH).
The increase in ADH causes more aquaporin utilisation in the collecting duct system of the kidney. This causes more water to be retained, diluting the electrolytes in the blood and making the electrolytes in the urine more concentrated.
Small cell lung cancer is a common cause of SIADH and is the most likely diagnosis in this man with an extensive smoking history, cough and weight loss.
SIADH and CAP - Example Question
An elderly male presents with a 2 week history of breathlessness. His past medical history includes diet-controlled type 2 diabetes, ischaemic heart disease, hypothyroidism and depression. His medication list includes levothyroxine, aspirin, simvastatin, ramipril, bisoprolol and citalopram. Observations on presentation to Emergency Department are as follows: respiratory rate 26/min, saturations 94% (on 4 litres oxygen via Venturi), heart rate 80 beats per minute, blood pressure 156/82 mmHg. Auscultation demonstrates crackles at the left base with no wheeze. The abdomen is soft and non-tender. There is no oedema peripherally.
Blood results on admission are provided below:
Hb 134 g/l Platelets 172 * 109/l WBC 13.3 * 109/l Na+ 128 mmol/l K+ 5.1 mmol/l Urea 13 mmol/l Creatinine 178 µmol/l Serum osmolality 220 mosm/kg Urinary sodium 50 mEq//l
What is the most likely cause of hyponatraemia?
Hypothyroidism Chronic kidney disease Addison's disease Salt-losing nephropathy > Syndrome of inappropriate antidiuretic hormone (SIADH)
This question demonstrates a common scenario in clinical practice. Management of hyponatraemia first requires clarification of fluid status (clinical hypovolaemia, euvolaemia or hypervolaemia), as differentials are influenced by this. This patient’s history, examination findings and haemodynamic parameters are consistent with clinical euvolaemia.
Differentials for euvolaemic hyponatraemia would include hypothyroidism and SiADH. There are no clinical features suggestive of the former. Findings are consistent with community-acquired pneumonia with associated SiADH. This is confirmed by the presence of reduced serum osmolality and high urinary sodium. Measurement of urinary sodium concentration is an useful adjunct in helping to differentiate between hyponatraemia secondary to hypovolaemia and SiADH. With SiADH (and salt-wasting syndrome), the urinary sodium is high. With hypovolaemia, the urinary sodium is typically low.
ADH
ADH is secreted from the posterior pituitary gland - promotes water reabsorption in collecting ducts of kidneys by insertion of aquaporin-2-channels
SOURCE = synthesised in supraoptic nuclei of the hypothalamus, released by pituitary
FUNCTION = Conserves body water! Promotes water reabsorption in the collecting ducts of the kidneys by insertion of aquaporin-2-channels
Regulation: INCREASES SECRETION OF ADH - ECF osmolality increase - volume decrease - pressure decrease - angiotensin II
DECREASES SECRETION OF ADH
- ECF osmolality decrease
- volume increase
- temperature decrease
NB Diabetes insipidus is either a deficiency of ADH (Cranial) or an insensitivity to ADH (Nephrogenic)
Cranial DI can therefore be treated with ADH analogue! = Desmopressin
SIADH Mx
The initial treatment option for SIADH is by fluid restriction which, under most circumstances, will correct the biochemical abnormalities in almost every case.
Demeclocycline (reduced responsiveness of collecting tubule cells to ADH) is indicated if fluid restriction is poorly tolerated or ineffective.
Hypertonic saline is indicated only when the syndrome is very severe, acute and symptomatic.
Cerebral Salt Wasting Syndrome vs SIADH
Both can occur after Neurosurgery Both = Hyponatraemia BUT SIADH= Euvolaemic Cerebral Salt wasting syndrome = Hypovolaemic
Cerebral salt wasting syndrome can occur following neurosurgery. It occurs due to sodium wasting in the urine. Comparatively to SIADH which is managed with fluid restriction, it is treated with replacing fluid and sodium losses.
THINK SIADH IF:
EUVOLAEMIC
HYPONATRAEMIC
HIGH URINE OSMOLALITY
REDUCED PLASMA OSMOLALITY
Increase in ADH = more aquaporin utilisation in the collecting duct system of the kidney = more water retained = dilutes the electrolytes in the blood making the electrolytes in the urine more concentrated.
