Write a short note on diabetes insipidus.

Definition

Diabetes insipidus (DI) is a disorder of water balance characterised by the passage of large volumes of dilute urine (polyuria) with compensatory polydipsia, resulting from either deficient secretion of antidiuretic hormone (ADH, vasopressin) or renal resistance to its action. Polyuria is conventionally defined as urine output exceeding 3 litres per day in adults.

Physiology

ADH is synthesised in the supraoptic and paraventricular nuclei of the hypothalamus and stored in and released from the posterior pituitary in response to rising plasma osmolality and to hypovolaemia. It acts on V2 receptors in the renal collecting duct, inserting aquaporin-2 water channels and permitting water reabsorption. Loss of this mechanism produces dilute urine and water loss.

Classification and Causes

Clinical Features

• Polyuria, nocturia and polydipsia with a craving for cold water, and passage of large volumes of dilute, colourless urine.
• If the thirst mechanism is intact and water is accessible, the patient remains eugly­caemic and near-eunatraemic — the illness is one of inconvenience.
• Dehydration and hypernatraemia develop rapidly if access to water is restricted — in infants, the unconscious, the elderly, the postoperative patient, and those with hypothalamic damage impairing thirst. Features then include lethargy, irritability, weakness, fever, confusion, seizures and coma.
• Features of the underlying cause — headache, visual field defect and other pituitary deficiencies in cranial DI; drug history in nephrogenic DI.

Investigations

Step 1 — confirm true polyuria and exclude common mimics:

Measure 24-hour urine volume; exclude diabetes mellitus (osmotic diuresis), hypercalcaemia, hypokalaemia, chronic kidney disease and diuretic use.

Step 2 — paired plasma and urine osmolality:

• DI: high or high-normal plasma osmolality (> 295 mOsm/kg) with inappropriately dilute urine (< 300 mOsm/kg).
• Primary polydipsia: low plasma osmolality with dilute urine — the plasma osmolality is the discriminator.

Step 3 — water deprivation test with desmopressin, the classic confirmatory investigation:

The test must be supervised with hourly weights and plasma sodium, and stopped if weight falls by more than 3–5% or sodium rises significantly. Copeptin measurement (a stable ADH surrogate), particularly after hypertonic saline or arginine stimulation, is increasingly replacing the water deprivation test where available.

Step 4 — establish the cause: MRI pituitary and hypothalamus (loss of the normal posterior pituitary "bright spot" on T1 supports cranial DI); assess other pituitary axes; serum calcium, potassium, renal function; drug review; and investigation for infiltrative disease.

Management

Cranial DI:

• Desmopressin (DDAVP) — a synthetic ADH analogue with V2 selectivity, available as intranasal spray, oral tablets, sublingual melt or injection. Titrate to control symptoms while allowing a brief period of breakthrough diuresis each day to avoid water retention.
• Ensure free access to water and maintain thirst-guided drinking.
• Treat the underlying cause — tumour, tuberculosis, sarcoidosis; replace other pituitary hormones as needed.

Nephrogenic DI:

• Remove or substitute the causative drug where possible (lithium — in consultation with psychiatry), and correct hypokalaemia and hypercalcaemia.
• Adequate water intake; low-salt, low-protein diet to reduce solute load.
• Thiazide diuretics — paradoxically antidiuretic in DI, by inducing mild volume depletion with increased proximal reabsorption; often combined with amiloride (particularly useful in lithium-induced DI, as it blocks lithium entry into collecting duct cells).
• NSAIDs (indomethacin) — reduce renal prostaglandin-mediated antagonism of ADH.
• Desmopressin is ineffective, though very high doses may partially help some incomplete forms.