Pedia News

Hypernatraemia and Diabetes Insipidus


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 and Diabetes Insipidus

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.