Best Practice & Research Clinical Endocrinology & Metabolism 26 Suppl.

1 (2012) S7–S15

Contents lists available at ScienceDirect

Best Practice & Research Clinical

Endocrinology & Metabolism
journal homepage: www.elsevier.com/locate/beem

Differential diagnosis of hyponatraemia

Chris Thompson MD FRCPIa, *, Tomas Berl MDb,A , Alberto Tejedor MD PhDc,B ,
Gudmundur Johannsson MD PhDd,C
a AcademicDepartment of Endocrinology, Beaumont Hospital and RCSI Medical School, Beaumont Road, Dublin 9, Ireland
b Division
of Renal Diseases and Hypertension, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, USA
c Department of Nephrology, Laboratory of Renal Physiopathology, Hospital General Universitario Gregorio Marañón, Doctor
Esquerdo 46, 28007 Madrid, Spain
d Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Göteborg, S-413 45 Göteborg, Sweden

Keywords: The appropriate management of hyponatraemia is reliant on

algorithm the accurate identification of the underlying cause of the
diagnosis hyponatraemia. In the light of evidence which has shown that
hyponatraemia the use of a clinical algorithm appears to improve accuracy
syndrome of inappropriate secretion of
in the differential diagnosis of hyponatraemia, the European
antidiuretic hormone (SIADH)
sodium
Hyponatraemia Network considered the use of two algorithms.
One was developed from a nephrologist’s view of hyponatraemia,
while the other reflected the approach of an endocrinologist. Both
of these algorithms concurred on the importance of assessing
effective blood volume status and the measurement of urine
sodium concentration in the diagnostic process. To demonstrate the
importance of accurate diagnosis to the correct treatment of hy-
ponatraemia, special consideration was given to hyponatraemia in
neurosurgical patients. The differentiation between the syndrome
of inappropriate antidiuretic hormone secretion (SIADH), acute
adrenocorticotropic hormone (ACTH) deficiency, fluid overload and
cerebral salt-wasting syndrome was discussed.
In patients with SIADH, fluid restriction has been the mainstay
of treatment despite the absence of an evidence base for its use.
An approach to using fluid restriction to raise serum tonicity in
patients with SIADH and to identify patients who are likely to be
recalcitrant to fluid restriction was also suggested.
© 2012 Elsevier Ltd. All rights reserved.

* Corresponding author. Chris Thompson. Tel.: +353 183 76532; Fax: +353 183 76501.
E-mail address: christhompson@beaumont.ie.
A
Tel: +1 303 7244803; Fax: +1 303 7244868. E-mail address: tomas.berl@ucdenver.edu.
B
Tel: +34 91 4265145; Fax: +34 91 5868214. E-mail address: atejedor@nefro.hggm.es.
C
Tel: +46 31 3423101; Fax: +46 31 821524. E-mail address: gudmundur.johannsson@medic.gu.se.

This supplement was commissioned by Otsuka Pharmaceutical Europe Ltd.

The European Hyponatraemia Network Academy meeting was organised and supported by Otsuka Pharmaceutical
Europe Ltd.

1521-690X/$ – see front matter © 2012 Elsevier Ltd. All rights reserved.
S8 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15

1. Introduction
Hyponatraemia, defined as a serum sodium concentration ([Na+ ]) <136 mmol/L, is the most commonly
encountered electrolyte disorder in clinical practice.1 However, evidence from the literature indicates
that the condition is often overlooked with patients remaining untreated.2,3 Successful treatment of
hyponatraemia depends upon accurate diagnosis of the underlying aetiology of hyponatraemia; again,
published data show that in many cases, clinicians do not order the appropriate tests to enable them to
arrive at the correct diagnosis.3 Unfortunately, there is no consensus on the best diagnostic approach to
uncover the primary cause of hyponatraemia. Experts from different specialties often propose different
diagnostic algorithms to facilitate the management of hyponatraemic patients in the hospital setting.
Traditionally, diagnosis and treatment of hyponatraemia has fallen within the remit of practitioners of
nephrology and endocrinology. Therefore, endocrinologists and nephrologists were brought together at
the European Hyponatraemia Network Academy Meeting to discuss two approaches to the differential
diagnosis of hyponatraemia using different diagnostic algorithms. The intention of this article is to
highlight the importance of clinical and biochemical evaluations of patients with hyponatraemia and
to utilise the approach to the differential diagnosis of neurosurgical hyponatraemia as an example of
a complex differential diagnostic entity.

2. Algorithms for the diagnosis of hyponatraemia: a nephrologist’s view

The management of hyponatraemia requires an approach that identifies the underlying cause of the
electrolyte disorder. From a nephrologist’s vantage point, the following algorithm is proposed. One
approach to this involves the sequential assessment of serum tonicity, urine osmolality, volume status
and urinary [Na+ ].

2.1. Assessment of serum tonicity

Sodium is the predominant solute in the extracellular fluid compartment and, as such, the primary
determinant of serum tonicity. A decrease in serum [Na+ ] (i.e. hyponatraemia) generally, but not always,
reflects a state of hypotonicity. The presence of an increased concentration of solutes that do not cross
the cell membrane (such as glucose, mannitol or glycine) can lead to the development of translocational
hyponatraemia as a result of the movement of water from the cells to the extracellular space. Such
patients can have normal, or even high, serum osmolality. Another setting in which hyponatraemia is
associated with a normal serum tonicity occurs in the presence of high levels of lipids or proteins.4
This is designated as pseudohyponatraemia and is the result of the increased proportion of serum
volume taken up by these substances. The serum osmolality remains normal in pseudohyponatraemia
and can be used to eliminate this diagnosis.5

2.2. Assessment of urine osmolality

Once the presence of hypotonicity has been established, the urinary osmolality may be used to
differentiate between patients who do and do not have a disorder in the renal diluting mechanism.4
A urine osmolality below 100 mOsm/kg reflects a normal diluting mechanism, the hyponatraemia
resulting from a level of water intake that exceeds normal urinary diluting capacity (psychogenic
polydipsia). This can also be observed in infants fed dilute formula and patients with a low solute
intake. In contrast, a urine osmolality exceeding 100 mOsm/kg reflects impairment to the renal diluting
mechanism at a time when the urine should be maximally dilute in the setting of serum hypotonicity,
this most commonly is a consequence of persistent vasopressin in the circulation.4

2.3. Assessment of volume status and urinary sodium concentration

In patients whose urine osmolality is greater than 100 mOsm/kg, assessment of volume status is
necessary to identify the underlying aetiology of the hyponatraemia. In hypovolaemic patients with
hyponatraemia, urinary [Na+ ] greater than 20 mmol/L is indicative of renal sodium losses, whereas a
 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15 S9

urinary [Na+ ] below 20 mmol/L reflects extra renal sodium losses. The potential underlying causes of
hyponatraemia in both these circumstances are outlined in Fig. 1.4

Hypotonic hyponatraemia

Assess volume status

Hypovolaemia Euvolaemia Hypervolaemia

Measure urinary [Na+] Measure urinary [Na+]

> 20 mmol/L < 20 mmol/L Urinary [Na+] > 20 mmol/L > 20 mmol/L < 20 mmol/L
Renal losses Extrarenal losses

Diuretic excess Vomiting Glucocorticoid deficiency Acute or chronic Nephrotic syndrome

renal failure
Mineralocorticoid Diarrhoea Hypothyroidism Cirrhosis
deficiency Pregnancy
Third spacing of Drugs Heart failure
Salt-losing nephropathy fluids in burns,
SIADH
pancreatitis and
Bicarbonaturia with
trauma
renal tubular acidosis
and metabolic alkalosis
Ketonuria
Cerebral salt-wasting
syndrome

Fig. 1. Algorithm for the differential diagnosis in a patient with hypotonic hyponatraemia. Adapted from Chonchol M & Berl T.
Hyponatraemia. In: DuBose T & Hamm L (eds). Acid-base and electrolyte disorders: a companion to Brenner and Rector’s The Kidney,
pp 229–240. Saunders; 2002.4

Patients with hypervolaemic hyponatraemia (due to heart failure, cirrhosis and nephrotic syndrome)
characteristically also have a sodium retaining disorder in addition to the water retention reflected
in the decrement of sodium serum. Thus, their urinary sodium is <20 mmol/L. Less commonly,
hypervolaemic hyponatraemia is seen in patients with advanced renal failure who cannot conserve
sodium, and therefore may have a urinary [Na+ ] >20 mmol/L.4
In euvolaemic hyponatraemia there is an excess of total body water relative to a normal amount of
total body sodium. These patients characteristically have a urinary sodium >20 mmol/L, as this reflects
their sodium intake.

3. Algorithms for the diagnosis of hyponatraemia: an endocrinologist’s view

The key to the differential diagnosis of hyponatraemia is:
1. The estimation of the blood volume of the patient.
2. The measurement of urine sodium concentration.
The algorithm used in practice is shown in Table 1.

3.1. Classification of volume status

The classification of the patient’s volume status (as euvolaemic, hypervolaemic or hypovolaemic) is
a critical first step in the diagnosis of the underlying aetiology of hyponatraemia. Bedside evaluation
of the patient relies on a thorough physical examination;6 the key clinical parameters to aid the
judgement of the clinician are shown in Table 1. The most useful is the measurement of central venous
pressure, but this is invasive and not always available. In addition to clinical evaluation, biochemical
S10 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15

parameters such as blood urea and creatinine are valuable. Plasma renin activity is potentially a very
sensitive marker of blood volume status but the results rarely come back in time to make a meaningful
contribution to what remains a predominantly clinical judgement. In many cases it can be difficult
to determine volume status, and the endocrinologist’s view would be that an algorithm is a useful
guideline, which still requires experienced clinical acumen for optimum use.

Table 1
Proposed matrix for the differential diagnosis of the underlying aetiology of hyponatraemia. Diagnosis of the underlying
aetiology of the hyponatraemia using this system relies on an accurate assessment of the patient’s volume status and
measurement of urinary [Na+ ].

Urine [Na+ ] <20 mmol/L Urine [Na+ ] >40 mmol/L

Hypovolaemia Vomiting, diarrhoea, Diuretics, Addison’s,
(dry tongue, decreased CVP, increased urea, skin losses, burns cerebral salt-wasting syndrome,
increased pulse, decreased BP) salt-losing nephropathy
Euvolaemia Hypothyroidism SIADH
Any cause + hypotonic fluids Glucocorticoid deficiency
Drugs
Hypervolaemia CCF, cirrhosis Renal failure, any cause + diuretics
(oedema, ascites, LVF, increased JVP, Nephrotic syndrome
increased CVP)

BP = blood pressure; CCF = congestive cardiac failure; CVP = central venous pressure; LVF = left ventricular failure; JVP = jugular
venous pressure; SIADH = syndrome of inappropriate secretion of antidiuretic hormone.
Presented by Prof. Thompson at the European Hyponatraemia Network Academy meeting in February 2011.

Distinguishing hypovolaemic hyponatraemia from euvolaemic hyponatraemia can be particularly

problematic. Hypovolaemic hyponatraemia is typically recognised by clinical signs such as a dry
tongue, decreased central venous pressure, increased urea, increased pulse and decreased blood
pressure. However, evidence suggests that the detection of mild-to-moderate volume contraction may
be difficult in clinical practice.7 Many clinicians find that the differentiation between mild volume
depletion and euvolaemia is difficult and that recommended clinical and biochemical parameters are
insufficiently reliable to accurately make the distinction. In practice, a common approach is to treat
‘grey cases’ as if they had volume depletion, and administer intravenous saline when in diagnostic
doubt; however, in any case, the osmolality of the infusate must be higher than the osmolality of the
urine in order to prevent worsening of the hyponatraemia.
Typically, hypervolaemic hyponatraemia is more easily recognised, by the presence of peripheral or
sacral oedema, signs of pulmonary oedema, ascites, increased jugular venous pressure and increased
central venous pressure. Euvolaemia may be diagnosed in the absence of any clinical signs of volume
depletion or volume expansion, as outlined above.8
Following determination of the volume status, the next step in the differential diagnosis of
hyponatraemia is the assessment of urinary [Na+ ]. In patients with hypovolaemic hyponatraemia,
a urinary [Na+ ] <20 mmol/L is indicative of extra renal solute loss, such as that caused by vomiting,
diarrhoea, skin losses and burns. Secondary hyperaldosteronism develops, with reabsorption of sodium
at the renal tubules, and a fall in urine sodium concentration. In contrast, a urinary [Na+ ] >40 mmol/L
indicates that the mineralocorticoid effects of secondary hyperaldosteronism are not conserving renal
sodium. This is indicative of renal solute loss and demonstrates that the kidney is the site of the
problem. Thiazide diuretic use is the commonest cause of hypovolaemic hyponatraemia with high
urine [Na+ ]. Primary adrenal insufficiency, with loss of aldosterone and cortisol secretion also falls into
this category, as do cerebral salt-wasting syndrome and salt-losing nephropathy. Urine [Na+ ] between
20–40 mmol/L may occur in patients with renal or extra-renal sodium loss and is a diagnostic grey
area which still requires individual clinical judgement. In patients with hypervolaemia, a urinary [Na+ ]
<20 mmol/L is indicative of congestive cardiac failure, cirrhosis or nephrotic syndrome; all of these
conditions are characterised by secondary hyperaldosteronism, with renal sodium reabsorption. In
contrast, hypervolaemic hyponatraemia and a urinary [Na+ ] >40 mmol/L suggest the hyponatraemia
results from renal failure.
 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15 S11

It is important to recognise a number of caveats to the use of algorithms:

1. They are only guidelines, and it is important to exercise clinical acumen in the application of all
algorithms.
2. Differential diagnosis of hyponatraemia can be complicated in patients receiving diuretics; diuretics
decrease the reabsorption of sodium within the nephron and increase urinary sodium excretion.
They can affect the clinical presentation and laboratory results for hyponatraemia, and may lead
to misdiagnosis. Diseases classified as typically associated with low urine [Na+ ] may present with
high urine [Na+ ].7 Consequently, urinary sodium excretion should be used cautiously as a diagnostic
marker in patients treated with diuretics.9 In these patients, fractional uric acid excretion (FE-UA)
can instead be used to aid the differential diagnosis of hyponatraemia, particularly in differentiating
between SIADH and hypovolaemic hyponatraemia (an FE-UA cut-off value of 12% appears to be
optimal to confirm the diagnosis of SIADH [positive predictive value of 100%], whereas an FE-UA
<8% excludes SIADH).9
3. Spot urine sodium measurements are not always accurate but are often all that is available in the
early assessment of hyponatraemia. This is the reason for the grey area in the algorithm, between
20–40 mmol/L.
4. Some patients may have several causes of hyponatraemia simultaneously, the patient with
pneumonia who is vomiting and is already on diuretics for instance. In cases of diagnostic doubt,
slow intravenous infusion of isotonic saline is the safest initial course.
Euvolaemia and a urinary [Na+ ] <20 mmol/L is seen in severe hypothyroidism or the administration
of hypotonic fluids. Excretion of more concentrated urine (i.e., with [Na+ ] >40 mmol/L) in patients
with euvolaemia is typical of SIADH. It is important to recognise that glucocorticoid insufficiency
may present with a biochemical profile of SIADH, and is only recognised if the clinician has a high
enough index of suspicion to measure serum cortisol or perform a dynamic test of cortisol secretion.
Published data have stressed the importance of performing sufficient diagnostic tests to eliminate
other potential causes of hyponatraemia, in order to avoid misdiagnosing SIADH.3,7 The essential and
supporting diagnostic criteria for SIADH have been published (outlined in Table 2).10,11

3.2. Differential diagnosis of hyponatraemia in a neurosurgical patient population

In a neurosurgical patient population, hyponatraemia may be attributable to SIADH, injudicious use
of IV fluids, acute ACTH deficiency or, rarely, cerebral salt-wasting syndrome. Table 3 summarises the
causes of neurosurgical hyponatraemia and their treatment. It is particularly important to exclude
ACTH deficiency in patients with hyponatraemia, particularly in the presence of hypotension and
hypoglycaemia; 16% of patients with acute head injury, for instance, develop acute ACTH deficiency.12
Differentiation between SIADH and cerebral salt wasting is sometimes regarded as problematical,
though the authors do not believe that the latter is commonly seen. However, the differentiation
has important implications for the appropriate selection of treatment, because fluid restricting a
patient with cerebral salt-wasting syndrome (incorrectly diagnosed as SIADH) may lead to worsening
of hyponatraemia and could dangerously impact on patient outcomes,13 potentially leading to acute
and chronic neurological sequelae.14
Cerebral salt-wasting syndrome was first described by Peters et al. (1950), in three patients with
neurological disorders and hyponatraemia, volume depletion, diuresis, natriuresis and a normal
hypothalamic-pituitary-adrenal axis.15 Since then, there have been reports in the literature of
hyponatraemia associated with volume depletion in patients with intracranial disease.16–18 Cerebral
salt-wasting syndrome has now been described in association with several conditions, including
subarachnoid haemorrhage, pituitary surgery, infectious meningitis and carcinomatous meningitis and
following injury or surgery to the central nervous system.13
There is some debate in the literature regarding the relative frequency of SIADH or cerebral
salt-wasting syndrome as causes of hyponatraemia in neurosurgical patients.14,19,20 However, the
authors’ view is that cerebral salt wasting is an uncommon cause of hyponatraemia in neurosurgical
hyponatraemia. A retrospective review of 102 patients with traumatic brain injury identified one
possible case of cerebral salt wasting out of 20 patients who developed hyponatraemia21 and a
prospective study of 50 patients carried out by the same group defined no cases of cerebral salt
S12 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15

Table 2
Essential and supporting criteria for the diagnosis of hyponatraemia secondary to SIADH. These diagnostic criteria should be
used to confirm a diagnosis of hyponatraemia secondary to SIADH.10,11

Essential diagnostic criteria for SIADH

• Decreased measured serum osmolality (<275 mOsm/kg H2 O)
• Urinary osmolality >100 mOsm/kg H2 O during hypo-osmolality
• Clinical euvolaemia
◦ No clinical signs of contraction of extracellular fluid (e.g., no orthostasis a , tachycardia, decreased skin turgor or dry
mucous membranes)
◦ No clinical signs of expansion of extracellular fluid (e.g., no oedema or ascites)
• Urinary [Na+ ] >40 mmol/L with normal dietary sodium intake b
• Normal thyroid and adrenal function determined by both clinical and laboratory assessment
• No use of diuretic agents within the week prior to evaluation

Supporting diagnostic criteria for SIADH

• Serum uric acid <4 mg/dL (<0.24 mmol/L)
• Blood urea nitrogen <10 mg/dL (<3.57 mmol/L)
• Fractional sodium excretion >1%; fractional urea excretion >55% c
• Failure to improve or worsening of hyponatraemia after 0.9% saline infusion
• Improvement of hyponatraemia with fluid restriction
a Orthostatic changes in blood pressure and pulse rate are defined as a ≥20 mmHg decrease in systolic blood pressure and/or
a ≥20 bpm increase upon going from a supine to a standing position.
b Although high urine sodium excretion generally occurs in patients with SIADH, its presence does not confirm the diagnosis,

nor does its absence rule out the diagnosis; urine [Na+ ] can also be high in patients with Addison’s disease. Conversely,
some patients with SIADH can have low urinary [Na+ ] if they become hypovolaemic or solute depleted, which are conditions
sometimes produced by imposed sodium and water restriction.
c Fractional sodium excretion = (urinary sodium excretion/serum sodium)/(urinary creatinine/serum creatinine) × 100;

Fractional urea excretion = (urinary urea/serum urea)/(urinary creatinine/serum creatinine) × 100.

Adapted from Ellison DH et al. N Engl J Med 2007; 356: 2064–2072.10

Table 3
The causes of neurosurgical hyponatraemia and their treatment.

Causes of neurosurgical hyponatraemia Blood volume status Treatment

SIADH Euvolaemia Fluid restriction

Acute ACTH deficiency Euvolaemia Glucocorticoids
Excess IV fluids Hypervolaemia Reduce fluids/diuretics
Diuretic therapy Hypovolaemia IV saline
Carbamazepine Euvolaemia Alternative seizure therapy
Cerebral salt wasting Hypovolaemia Aggressive IV saline
Combinations of the above Variable Underlying aetiology

ACTH = adrenocorticotropic hormone; IV, intravenous; SIADH = syndrome of inappropriate secretion of antidiuretic hormone.

wasting.12 Although the same authors estimated that cerebral salt wasting may have been responsible
for 6.5% of cases of hyponatraemia following subarachnoid haemorrhage, the data were derived from a
case note review and were incomplete in some cases.14 A subsequent prospective study of 100 patients
with subarachnoid haemorrhage showed that of 49 patients with hyponatraemia, none had cerebral
salt wasting; SIADH was responsible for 71% of cases and ACTH deficiency for 10%.22
 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15 S13

Although cerebral salt wasting is rare, the authors do believe it exists as an entity separate from
SIADH. There are several shared characteristics of SIADH and cerebral salt-wasting syndrome (outlined
in Table 4); both conditions are associated with a low serum [Na+ ] and an elevated urinary [Na+ ].14 The
main feature unique to cerebral salt-wasting syndrome is the presence of clinical hypovolaemia – as
a result of this volume depletion, patients may exhibit signs such as hypotension or reduced skin
turgor.13,23 The mechanism of cerebral salt-wasting syndrome is yet to be well defined, although
evidence from patients who experienced subarachnoid haemorrhage suggests that the inappropriately
elevated secretion of atrial and brain natriuretic peptides contribute to hyponatraemia following
neurosurgery.24,25

Table 4
Characteristics of SIADH and cerebral salt-wasting syndrome. For a diagnosis of SIADH, the criteria outlined in Table 2
should be used to confirm diagnosis.

SIADH Cerebral salt-wasting syndrome

Serum [Na+ ] Low Low
Blood urea Normal/low Raised
BP Normal Normal/postural fall
Urine volume Low High
Urinary [Na+ ] Raised Raised
CVP Normal Low

BP = blood pressure; CVP = central venous pressure; SIADH = syndrome of inappropriate secretion of antidiuretic hormone.
Reproduced from Sherlock M et al. Postgrad Med J 2009; 85: 171–175.14 With permission.

Regardless of the mechanism of cerebral salt-wasting syndrome, its treatment is dependent on

restoring the patient’s volume status through the administration of isotonic saline;13 therefore, fluid
restriction is not appropriate and, as mentioned previously, may worsen the condition. In contrast,
patients with SIADH may be treated with fluid restriction or a vasopressin receptor antagonist (vaptan).
Neurosurgeons are reluctant to contemplate fluid restriction because of their perception that volume
expansion is integral to the management of subarachnoid haemorrhage. It has been noted that there
is a paucity of data regarding the use of vaptans in the neurosurgical patient. It is crucial to confirm
that SIADH is the true cause of the hyponatraemia prior to administration13 as a misdiagnosis may
lead to incorrect treatment that may worsen the hyponatraemia. Consequently, the initial monitoring
of therapy should always be rigorous regardless of the choice of therapy.

4. Summary
Accurate diagnosis of hyponatraemia is necessary to determine appropriate treatment and algorithms
can be developed and used to aid this process. However, clinical acumen is still important as algorithms
should act only as guidance, and are of most use when applied by physicians who understand them.
While diagnostic approaches for hyponatraemia can vary, the careful assessment of volume status
and urinary [Na+ ] is critical, as outlined in both of the approaches in this article. In neurosurgical
hyponatraemia, differentiation between euvolaemia and hypovolaemia is essential for the diagnosis
of SIADH and cerebral salt-wasting syndrome, respectively.

5. Acknowledgements
This supplement was commissioned by Otsuka Pharmaceutical Europe Ltd. and summarises the
proceedings of a meeting organised and supported by Otsuka Pharmaceutical Europe Ltd. The authors
have not received any honorarium in relation to this supplement. Otsuka Pharmaceutical Europe Ltd.
has had the opportunity to comment on the medical content and accuracy of the article and editorial
support has been provided by Otsuka Pharmaceutical Europe Ltd.; however, final editorial content
resides with the authors and Best Practice & Research: Clinical Endocrinology & Metabolism.
S14 C. Thompson et al. / Best Practice & Research Clinical Endocrinology & Metabolism 26 (2012) S7–S15

Practice points

• In patients with serum hypotonicity, translocational hyponatraemia and pseudohypona-

traemia must be ruled out before a diagnosis of hyponatraemia can be made.
• Differential diagnosis of the aetiology of the hyponatraemia requires assessment of volume
status and urine sodium concentration.
• In neurosurgical patients, hyponatraemia is caused most frequently by SIADH or acute ACTH
deficiency; cerebral salt-wasting syndrome is rare. It is important to differentiate between
these conditions (and to rule out any alternative causes of hyponatraemia) before initiating
treatment.
• SIADH may be treated with fluid restriction, though neurosurgeons are reluctant to
contemplate this in subarachnoid haemorrhage patients. Vasopressin receptor antagonists
offer an alternative treatment but have not been studied in the neurosurgical context. Acute
ACTH deficiency requires glucocorticoid therapy and the rare cerebral salt-wasting syndrome
may be treated by administration of 0.9% isotonic saline.

Research agenda

• There is a need to further elucidate the mechanisms underlying hyponatraemia in patients

with cerebral salt-wasting syndrome.
• The usefulness of proposed algorithms in the differential diagnosis of the underlying aetiology
of hyponatraemia needs to be assessed in a clinical setting.

6. Conflict of interest
Prof. Thompson is on the Otsuka Pharmaceutical advisory board for tolvaptan and has received
honoraria from Otsuka Pharmaceutical for speaking at symposia. Prof. Berl is on the Otsuka
Pharmaceutical advisory board for tolvaptan and has received honoraria from Otsuka Pharmaceutical
for speaking at symposia. Dr. Tejedor acts as an expert in nephrology for the European Medicines
Agency and belongs to the Steering Committee of the European Hyponatraemia Network. He has
been scientific advisor for drugs related to the kidney: torasemide (Boehringer Ingelheim) and
tolvaptan (Otsuka Pharmaceutical Europe Ltd.). Dr. Tejedor also owns a patent on cilastatin as a broad
nephroprotector. Prof. Johannsson has received honoraria from Otsuka Pharmaceutical for speaking at
symposia.

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