Diabetes Insipidus

Definition/diagnostic criteria
Diabetes insipidus (DI) is a condition characterised by the inability of the kidneys to conserve water, leading to excessive urination (polyuria) and thirst (polydipsia). It is caused by either a deficiency in antidiuretic hormone (ADH), also known as vasopressin, or by renal insensitivity to ADH. There are two main forms: central DI, where ADH production or secretion is impaired (often due to damage to the hypothalamus or pituitary), and nephrogenic DI, where the kidneys are unresponsive to ADH. Diagnostic criteria include high urine output (>3 litres per 24 hours) with low urine osmolality (<300 mOsm/kg), accompanied by serum hyperosmolality (>295 mOsm/kg) and hypernatraemia in severe cases.

Epidemiology
Diabetes insipidus is relatively rare, with central DI being more common than nephrogenic DI. Central DI has an incidence of around 3 per 100,000 per year in the UK, while nephrogenic DI is rarer. Central DI may arise from a range of causes, including traumatic brain injury, pituitary surgery, tumours (e.g., craniopharyngiomas), infections, and autoimmune conditions. Nephrogenic DI may be congenital or acquired due to chronic lithium use, hypercalcaemia, or other renal diseases.

Diagnosis

Clinical features
The cardinal symptoms of DI include polyuria (usually producing dilute urine of more than 3 litres per day) and polydipsia. Patients often report an unquenchable thirst, particularly for cold water, and may wake frequently at night to urinate. In more severe cases or when fluid intake is restricted, dehydration, hypernatraemia, and hypotension may develop, leading to symptoms such as dizziness, fatigue, or confusion. Central DI typically presents suddenly, while nephrogenic DI can develop more insidiously.

Investigations
Initial assessment should include a thorough history and examination, including a focus on medication use (particularly lithium) and family history. Laboratory investigations include a 24-hour urine collection to quantify urine output. Key findings include polyuria and low urine osmolality, typically <300 mOsm/kg. Serum osmolality is typically raised (>295 mOsm/kg), often with hypernatraemia (>145 mmol/L), indicating dehydration.

A water deprivation test is the gold standard diagnostic test for differentiating DI from primary polydipsia. In central DI, water deprivation leads to continued polyuria with low urine osmolality, but administration of desmopressin (a synthetic vasopressin analogue) results in a rise in urine osmolality, indicating a response to ADH. In nephrogenic DI, there is little or no response to desmopressin, as the kidneys are unable to respond to the hormone.

Imaging, such as MRI of the brain, may be required to assess for structural abnormalities, particularly in cases of suspected central DI. A lack of the posterior pituitary ‘bright spot’ on MRI is indicative of impaired ADH secretion.

Treatment
The management of DI depends on the underlying cause. For central DI, the mainstay of treatment is desmopressin (DDAVP), which can be administered orally, intranasally, or via injection. Desmopressin acts as a replacement for the deficient ADH, helping to reduce polyuria and polydipsia. The dose should be titrated to avoid water intoxication, with regular monitoring of serum sodium and osmolality. In nephrogenic DI, desmopressin is ineffective, and treatment focuses on addressing the underlying cause (e.g., discontinuing lithium or correcting hypercalcaemia). Thiazide diuretics, often combined with a low-sodium diet, can paradoxically reduce urine output in nephrogenic DI by causing mild volume depletion, which encourages the kidneys to conserve water.

Non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin may also be used in nephrogenic DI to enhance the renal response to ADH by inhibiting prostaglandin synthesis, which otherwise antagonises the action of vasopressin in the kidneys.

Prognosis
With appropriate treatment, the prognosis for central DI is generally good, and most patients can lead normal lives with desmopressin therapy. However, underlying causes such as brain tumours or trauma may dictate overall prognosis. Nephrogenic DI can be more challenging to manage, particularly if it is congenital or due to irreversible renal damage. Patients with acquired nephrogenic DI often improve once the underlying cause is addressed, but long-term complications such as chronic dehydration and electrolyte imbalances may persist if treatment is suboptimal. Regular follow-up and monitoring are essential to ensure effective management and avoid complications such as hypernatraemia.