Diabetes Insipidus

Diabetes insipidus results from either deficient production of antidiuretic hormone (cranial or central DI, now increasingly termed arginine vasopressin deficiency) or renal resistance to its action (nephrogenic DI, arginine vasopressin resistance).

Either produces an inability to concentrate urine, with large volumes of dilute urine, compensatory thirst, and, if access to water is restricted, rapidly progressive hypernatraemia.

Cranial causes include pituitary surgery, head injury, tumours (craniopharyngioma, germinoma, metastases), infiltrative disease (sarcoidosis, Langerhans cell histiocytosis), and hypoxic brain injury. Nephrogenic causes include lithium (the commonest acquired cause and often only partially reversible), chronic hypercalcaemia, hypokalaemia, chronic kidney disease, and inherited channel defects.

• Polyuria, often substantial (>3 L/day, sometimes far more), including nocturia that disturbs sleep
• Polydipsia with a marked craving for cold water, which is a fairly characteristic description
• Urine that is persistently dilute and pale despite high output
• Signs of hypernatraemia if intake cannot keep pace: lethargy, irritability, weakness, confusion, and in severe cases seizures and coma

The danger point is any situation where the thirst mechanism is impaired or water is inaccessible, an unconscious patient, a post-operative patient, an infant, or an older adult with impaired thirst. In these settings serum sodium can climb quickly and dangerously, which is why fluid balance charting after pituitary surgery is not a formality.

• Confirm genuine polyuria with a 24-hour urine volume
• Paired serum and urine osmolality: the pattern is high or high-normal serum osmolality with inappropriately dilute urine (urine osmolality typically <300 mOsm/kg)
• Serum sodium is high or high-normal, in contrast to primary polydipsia where it tends to be low-normal
• Exclude the common mimics first: glucose (osmotic diuresis from uncontrolled diabetes mellitus), calcium, potassium and renal function
• Water deprivation test with desmopressin, performed under close supervision, distinguishes the causes: in cranial DI the urine concentrates after desmopressin; in nephrogenic DI it does not; in primary polydipsia the urine concentrates with deprivation alone
• Copeptin measurement, where available, is increasingly used and is more reliable and better tolerated than water deprivation testing
• MRI pituitary if cranial DI is confirmed, looking for structural pathology; loss of the normal posterior pituitary bright spot supports the diagnosis

Differentials: primary (psychogenic) polydipsia, osmotic diuresis from hyperglycaemia, diuretic use, and the polyuric phase of recovering acute kidney injury.

• Ensure free access to water at all times, and document this explicitly for any patient who cannot request drinks. Most of the serious harm in diabetes insipidus occurs when a patient with an intact compensatory mechanism is denied the ability to use it
• Accurate fluid balance and daily (or more frequent) sodium monitoring during the acute phase

Cranial DI:

• Desmopressin (DDAVP), given orally, intranasally or parenterally, titrated to control symptoms while avoiding over-treatment. The main hazard is hyponatraemia from excessive dosing combined with continued drinking, so patients are usually advised to allow a short period of breakthrough polyuria each day rather than aiming for complete suppression
• Treat the underlying cause; post-operative cranial DI may be transient, permanent, or follow a triphasic pattern of DI, then a period of SIADH-like antidiuresis, then permanent DI, a pattern worth anticipating after pituitary surgery, since the middle phase can produce dangerous hyponatraemia if desmopressin is continued unchanged

Nephrogenic DI:

• Remove or substitute the causative drug where possible; lithium requires a psychiatric discussion rather than unilateral withdrawal, and its effects may persist after discontinuation
• Correct hypercalcaemia and hypokalaemia
• Thiazide diuretics, counterintuitively, reduce urine output by inducing mild volume depletion and enhancing proximal reabsorption; often combined with a low-sodium diet
• Amiloride is particularly useful in lithium-induced DI, as it reduces lithium entry into collecting duct cells
• NSAIDs (indometacin) can be used as an adjunct, with the usual renal caution

Referral: endocrinology for all confirmed cranial DI and for water deprivation testing; nephrology for nephrogenic DI; neurosurgery where a pituitary or hypothalamic lesion is identified.