A 58-year-old man presented with confusion following a head injury from a car accident. Tests revealed hyponatremia with low serum osmolality and high urine osmolality, consistent with SIADH (syndrome of inappropriate antidiuretic hormone). SIADH was likely caused by the head injury. The man was placed on fluid restriction and his sodium levels began to rise. He improved with treatment and was discharged when his sodium levels normalized.

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Case 23 A 58-year-old type II diabetic with
confusion and hyponatraemia
Mr Sanjay Singh is a 58-year-old type II diabetic. He is
admitted following a road traffic accident with a head injury
and fractured tibia and fibula. Glasgow Coma Score (GCS)
on admission was 15 and a CT head did not show any
obvious fracture, haematoma or contusion. His lower limb
fractures are fixed in plaster of Paris (POP) and he is
admitted for observation and analgesia.
Bloods on admission are shown below.
Na 135mmol/L, K 4.0mmol/L, Urea 7.3mmol/L, Creatinine
112μmol/L, Glc 6.8mmol/L
Hb 15.8g/dL, WBC 5.7 × 109
/L, Platelets 230 × 109
/L
He is seen on ward round the next day and a plan is made
to discharge him later in the day. Unfortunately, he becomes
increasingly confused during the afternoon. His temperature
is 38o
C, pulse 90bpm, BP 145/85mmHg and JVP is visible.
He has no peripheral oedema. O2 saturations are 93% on air
and there are some crackles at the right base. There are no
focal neurological signs. Repeat bloods are shown below
and Mr Singh’s drug chart is shown in Figure 23.1.
Na 125mmol/L, K 3.8mmol/L, Urea 5.7mmol/L, Creatinine
108μmol/L, Glc 10.6mmol/L
Hb 15.5g/dL, WBC 6.2 × 109
/L, Platelets 353 × 109
/L
What is the most likely cause of
Mr Singh’s hyponatraemia?
The causes of hyponatraemia are summarised in Box
23.1. Mr Singh’s hyponatraemia is acute and he is not
obviously oedematous, fluid overloaded or dehydrated
(thus CCF, nephrosis, cirrhosis and diarrhoea are unlikely
to be the cause of his hyponatraemia). He is not on any
medications, particularly diuretics, which might directly
affect renal salt handling. We are not told anything about
Mr Singh’s fluid replacement regimen, therefore if he has
been given an excess of 5% dextrose in the past 36 hours,
this may have caused hyponatraemia. However, given
all of the above exclusions, the most likely diagnosis is
the syndrome of inappropriate antidiuretic hormone
(SIADH).
Review of Mr Singh’s fluid charts shows that he has had
free oral intake but no intravenous fluids.
What investigations would you
undertake to confirm the diagnosis
of syndrome of inappropriate
antidiuretic hormone?
Serum and urine osmolalities should be measured.
Plasma osmolality is usually kept within a tight range. In
SIADH there is dilute plasma with osmolalities of
<260mmol/kg and inappropriately concentrated urine
with urine osmolalities of >500mmol/kg. Urinary
sodium levels are usually >20mmol/L.
Mr Singh’s urine osmolality is 549mosmol/kg and his serum
osmolality is 258 mosmol/kg, confirming the diagnosis of
SIADH.
What is the likely cause of syndrome of
inappropriate antidiuretic hormone in
Mr Singh’s case?
Syndrome of inappropriate antidiuretic hormone can be
caused by many pathologies, as summarised in Box 23.2.
In this particular case, it is most likely to be due to head
injury. However, there may be other contributory fea-
tures. His examination findings suggest the possibility of
a right basal pneumonia (febrile, crackles at right base).
In addition, he has been given opiates for his pain and is
receiving chlorpropamide (see drug chart in Figure 23.1).
Where is antidiuretic hormone produced
and what are its actions?
Antidiuretic hormone (ADH, also known as vasopressin)
is produced in the hypothalamus, stored in vesicles in the
Nephrology: Clinical Cases Uncovered. By M. Clatworthy.
Published 2010 by Blackwell Publishing.

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SINGH
SANJAY
MRC BEECH
20/6/50
ASPIRIN
75mg
10mg
250mg
Ti
P0
P0
P0
P0
22/10
22/10
22/10
22/10
123
123
123
123
ATORvASTATIN
CHLORPROPAMIDE
COPROXAMOL
22/10 ul
M
A30694
Surname
First names
Consultant
Date of birth Sex
Ward
Weight
Height
Date Drug/substance
Drug sensitivities
Regular prescriptions
Month and date
Tick times or enter other times
1. Drug (approved name)
2. Drug (approved name)
3. Drug (approved name)
4. Drug (approved name)
5. Drug (approved name)
6. Drug (approved name)
Dose Route Start date Stop date
Dose Route Start date Stop date
Dose Route Start date Stop date
Dose Route Start date Stop date
Pharm
6
8
12
14
18
22
6
8
12
14
18
22
6
8
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14
18
22
6
8
12
14
18
22
6
8
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18
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6
8
12
14
18
22
Pharm
Signature:
Bleep no.:
Signature:
Bleep no.:
Pharm
Signature:
Bleep no.:
Pharm
Signature:
Bleep no.:
Dose Route Start date Stop date
Pharm
Signature:
Bleep no.:
Additional instructions
Additional instructions
Additional instructions
Additional instructions
Additional instructions
Dose Route Start date Stop date
Pharm
Signature:
Bleep no.:
Additional instructions
Doctor must enter this information on FRONT of case folder
Signature
Hospital No.
Prescription chart
Figure 23.1 Mr Singh’s prescription chart.

3. Case 23 161
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Antidiuretic hormone causes a more concentrated
urine to be produced by increasing the permeability to
water of the distal convoluted tubule and collecting
ducts, thus allowing an increase in water reabsorption
down the osmotic gradients set up by the loop of Henle.
This results in the excretion of a smaller volume of more
concentrated urine – antidiuresis.
Antidiuretic hormone increases permeability via the
insertion of additional water channels (aquaporin-2)
into the apical membrane of the tubules/collecting duct
epithelial cells. This is achieved through the action of
ADH on V2 receptors, G protein-coupled receptors on
the basolateral membrane of cells lining the distal con-
voluted tubules and conducting ducts.Following binding,
the G protein triggers the cAMP cascade which triggers
the insertion of aquaporin-2 water pores by exocytosis of
storage vesicles. The aquaporins then allow water to pass
out of the distal convoluted tubules and the conducting
tubules into the interstitium and back into the blood,
increasing the concentration of urine and expanding
blood volume.
Antidiuretic hormone also increases peripheral vascu-
lar resistance and thus mean arterial blood pressure. This
effect appears small in healthy individuals but may be an
important compensatory mechanism for restoring blood
pressure in hypovolaemic shock.
Antidiuretic hormone also has a number of actions
locally in the brain including:
• memory formation
• maintenance of circadian rhythm
• control of aggressive behaviour.
How would you manage
this patient?
The main management of SIADH is to restrict fluid
intake to 0.5–1L per day. This is usually in the form of
normal saline, if IV fluids are used (NB: normal (0.9%)
saline contains approximately 150mmol/L of Na). Occa-
sionally hypertonic saline is given but this requires
careful management to avoid a rapid increase in sodium
levels. The aim is to bring the sodium up by no more
than 5mmol/day. Severe cases may require the use of
demeclocycline, an agent which causes nephrogenic dia-
betes insipidus, i.e. it makes the collecting tubules insen-
sitive to the actions of ADH.
More recently, a new class of drugs has become
available in the form of specific V2 antagonists, for
example tolvaptan and satavaptan, which may be useful
in SIADH.
Box 23.1 Causes of hyponatraemia
• Inappropriate water retention – SIADH. Urine osmolality
is usually >500mosmol/kg (inappropriately concentrated
when compared with serum osmolality which tends to
be <260mosmol/kg)
• Excess water intake
䊊 Psychogenic polydipsia
䊊 Inappropriate IV fluids
• Combined Na + water retention with an excess of water
䊊 Congestive cardiac failure (CCF)
䊊 Nephrotic syndrome
䊊 Cirrhosis
• Salt loss
䊊 Renal: diuretics, Addison’s disease, salt-losing
nephropathy
䊊 GI: diarrhoea, villous adenoma
• Pseudohyponatraemia
䊊 Hypercholesterolaemia
䊊 Hyperproteinaemia
Box 23.2 Causes of SIADH
• Malignancy
䊊 Pancreatic cancer
䊊 Lymphoma
䊊 Small cell carcinoma of the lung
䊊 Prostate cancer
• CNS/neurological disorders
䊊 Abscess
䊊 Meningoencephalitis
䊊 Subarachnoid/subdural haemorrhage
䊊 Head injury
䊊 Guillain–Barré syndrome
• Pulmonary disorders
䊊 TB
䊊 Pneumonia
䊊 Pulmonary abscess/empyema
䊊 Aspergillosis
• Metabolic causes
䊊 Porphyria
• Drugs
䊊 Chlorpropamide
䊊 Opiates
䊊 Cytotoxins
䊊 Chlorpromazine
posterior pituitary and released in response to rising
plasma osmolality or a reduction in plasma volume/pres-
sure. Its main action is on the kidneys, causing water
retention and thus a more concentrated urine to be pro-
duced (as its name suggests).

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Why is important not to correct
hyponatraemia too quickly?
If plasma Na+ is corrected too quickly then central
pontine myelinolysis (CPM) can occur, where neurones
in the pontine region become demyelinated. This is
thought to be due to rapid fluid shifts out of the brain in
response to large increases in plasma sodium. Patients
rapidly develop para- or quadraparesis, dysphagia, dys-
arthria, diplopia and loss of consciousness. Diagnosis
is by clinical features and MRI (showing a high signal in
the pons).
Aim to correct plasma sodium by 5mmol/L/24h.
Maximum correction 8mmol/L/24h. Reports of CPM
have occurred where Na has risen by >10mmol/
L/24h.
Mr Singh is placed on a 1000mL fluid restriction over the
next 4 days. A chest X-ray confirms a likely right basal
Table 23.1 Causes of hypontraemia according to volume
status and urine Na excretion
Hypovolaemia Euvolaemia/
hypervolaemia
Urine Na+
>20mM Diuretics
Hypoadrenalism /
Addison’s
SIADH
Hypothyroidism
Chronic renal failure
Urine Na+
<20 mM Vomiting
Diarrhoea
LVF
Cirrhosis
Nephrotic syndrome
CASE REVIEW
A 58-year-old type II diabetic is admitted following an
accident. Over the next 36 hours he becomes confused.
Investigations show significant hyponatraemia (Na
125mmol/L), reduced serum osmolality and increased
urine osmolality in keeping with a diagnosis of SIADH.
This has probably been caused by the head injury sustained
during the accident. He is fluid restricted to 1L in 24 hours
and his sodium begins to rise. He improves rapidly and is
discharged 5 days later with a sodium of 136mmol/L.
KEY POINTS
• Mild hyponatraemia is common and usually asymptomatic.
If the sodium falls to around 120mmol/L then there is
often restlessness, irritability and confusion. Sodium levels
of <110mmol/L lead to progressive coma and seizures.
• Hyponatraemia occurs if there is too little sodium, too
much water or both.
• When assessing the cause of hyponatraemia, it is
important to establish the volume status of the patient.
• If the patient is hypovolaemic then hyponatraemia may be
caused by diuretics, hypoadrenalism, salt-wasting
nephropathy (see Table 23.1).
• If the patient is euvolaemic or fluid overloaded then
hyponatraemia may be due to SIADH, chronic renal
failure, LVF, cirrhosis or nephrotic syndrome (see
Table 23.1).
• In SIADH, typical findings are:
䊊 Na <125mmol/L
䊊 patient is normovolaemic
䊊 urinary Na >20mmol/L
䊊 plasma osmo <260mosmol/kg
䊊 urinary osmo >500mosmol/kg.
• Syndrome of inappropriate antidiuretic hormone may be
caused by intracranial pathology such as head injury or
infection, pulmonary pathologies including pneumonia,
malignancies and drugs (particularly chlorpropamide and
chlorpromazine).
• Treatment of SIADH is with fluid restriction. The aim
should be to bring the sodium up slowly in order to avoid
central pontine myelinolysis.
pneumonia and he is therefore commenced on appropriate
antibiotic therapy. His sodium rises from 125 to 129mmol/L
on day 1, to 132mmol/L on day 2 and to 136mmol/L by
day 3. He is finally discharged on oral antibiotics on day 6.