Hypernatraemia and Diabetes
Insipidus
Posterior pituitary function and sodium homeostasis
The posterior pituitary is derived from a down-growth of
primitive neural tissue and is anatomically distinct from the anterior
pituitary gland. The posterior pituitary has a vital role in sodium and water
balance, which is tightly regulated in health. Osmoreceptors in the
hypothalamic supraoptic nucleus respond to high serum osmolality by stimulating
vasopressin (ADH) release from the paraventricular nucleus in the hypothalamus
(Figure 7.1), as well as stimulating thirst. Vasopressin acts on aquaporin
channels in the collecting duct of the kidney to allow water reabsorption.
Osmolality quantifies the solute concentration of serum and can be measured
directly or calculated (2 × [Na+] + urea + glucose). In the absence of high
glucose and renal failure, osmolality amounts to approximately double serum
sodium. Rapid changes in osmolality can lead to catastrophic CNS consequences.
Hypernatraemia
Hypernatraemia is mild (Na 145–150 mmol/L), moderate (150–
159 mmol/L) or severe (>160 mmol/L). It is less common than hyponatraemia in
clinical practice but is a sign of significant disease. The causes are pure
water loss, hypotonic water loss or salt gain (Table 7.1). In patients with
hypernatraemia who have a high urine output and low urine osmolality, diabetes
insipidus (DI) should be considered.
Diabetes insipidus
DI is caused by vasopressin deficiency (cranial DI) or
reduced action of vasopressin on the kidney (nephrogenic DI). The lack of water
reabsorption from reduced vasopressin action leads to large volumes of dilute
urine with profound unquenchable thirst (Figure 7.1). The biochemical hallmarks
of DI are high serum osmolality, low urine osmolality and high urine volume.
Cranial DI is seen in inflammatory or infiltrative
pituitary disease (Figure 7.1). A strong family history of cranial DI suggests
a mutation in the arginine vasopressin (AVP) gene. DIDMOAD (Wolfram’s syndrome)
is a rare genetic condition characterised by DI, diabetes mellitus, optic
atrophy and deafness.
Nephrogenic DI is usually caused by metabolic and
electrolyte disturbance, renal disease and drugs affecting the kidney. A rare
congenital X-linked cause
of nephrogenic DI has also
been described.
Primary polydipsia is a behavioural condition leading to
polydipsia, which drives polyuria. It is not associated with hypernatraemia,
and can lead to dilutional hyponatraemia. Some patients with primary polydipsia
have an impaired ability to concentrate urine because of down-regulation of
vasopressin release, and this can occasionally be difficult to distinguish from
partial DI.
Investigation
DI is confirmed by demonstration of high urine volumes,
high serum osmolality and low urine osmolality. The clinical diagnosis is
usually obvious with complete vasopressin deficiency, due to the presence of
extreme thirst and passing of large quantities of pale urine. DI is confirmed
if serum osmolality >295 mosmol/kg, serum [Na+] >145 mmol/L and urine
osmolality <300 mosmol/kg.
Water deprivation test
In partial DI, the diagnosis may be less clear-cut. In this
situation a water deprivation test (WDT) can be useful. Patients with frank DI
will have severe thirst and lose significant weight as a result of water loss.
The test should be stopped if excessive weight loss occurs or symptoms are too
severe. DI is excluded if patients concentrate urine osmolality >600
mosmol/kg and serum osmolality remains <300 mosmol/kg. In the second part of
the WDT, synthetic vasopressin (1-desamino-8-d-arginine vasopressin; DDAVP) is
given. In cranial DI, DDAVP leads to reduced urine volume and increased urine
osmolality, while in nephrogenic DI there is no response.
Management
Patients with confirmed cranial DI should be investigated
for pituitary disease, and managed as appropriate. Cranial DI responds well to
DDAVP administration and results in good clinical improvement. Desmopressin can
be given intranasally, orally, sublingually or parenterally. Overtreatment with
DDAVP can lead to dilutional hyponatraemia, commonly characterised by headache
and reduced cognitive ability, and, less commonly, seizures if there is a
sudden drop in sodium. Signs of undertreatment with DDAVP are excessive thirst
and polyuria. Rarely, patients with DI have an impaired thirst mechanism if
there is hypothalamic involvement, termed hypodipsic DI. This can be seen in
hypothalamic infiltrative disorders and requires specialist care because of the
risk of severe hypernatraemia and dehydration.
In nephrogenic DI, the underlying cause should be
considered and reversed where possible. If symptoms persist, patients should
drink according to thirst and keep up with water loss. Specific measures to
treat nephrogenic DI include the use of low salt, low protein diet, diuretics,
and non-steroidal anti-inflammatory drugs (NSAIDs).
Acute severe hypernatraemia
This is a medical emergency and requires inpatient
management in a high dependency setting. Seizures and intracranial vascular
haemorrhage as a result of brain shrinkage can occur. Severe hypernatraemia (Na
>160 mmol/L) usually requires ITU discussion. The cause is most commonly
excessive water loss, and the key aspect of treatment is aggressive fluid
replacement. Normal (0.9%) saline should be given as initial fluid replacement,
as it is relatively hypotonic. An estimation of total body water deficit can be
made according to weight. If urine osmolality is low, DI should be considered,
and a trial of intramuscular or intravenous DDAVP given. In patients with known
DI, it is o ensure DDAVP is given parenterally, and that close fluid balance is
observed.
