Diabetes Insipidus
Cranial and nephrogenic DI — diagnosis, desmopressin and fluid management
Diabetes insipidus (DI) is a condition characterised by the production of large volumes of dilute urine (polyuria) and excessive thirst (polydipsia), caused by a deficiency of or resistance to antidiuretic hormone (ADH, also called vasopressin). It is entirely distinct from diabetes mellitus despite sharing the name. Without appropriate management, DI can cause life-threatening dehydration and hypernatraemia. Careful evaluation of the type and cause of DI guides specific treatment.
What is Diabetes Insipidus?
ADH (antidiuretic hormone, vasopressin) is produced in the hypothalamus and released from the posterior pituitary gland. It acts on the collecting ducts of the kidney to promote water reabsorption. In cranial DI, insufficient ADH is produced or released — often due to damage to the hypothalamus or pituitary from tumours, surgery, head injury, infiltrative disease (sarcoidosis, Langerhans cell histiocytosis), or may be idiopathic. In nephrogenic DI, ADH is produced normally but the kidneys fail to respond to it — caused by drugs (lithium, demeclocycline, amphotericin), hypercalcaemia, hypokalaemia, chronic kidney disease, or rare genetic mutations in the ADH receptor or aquaporin-2 genes. A third form — dipsogenic (primary polydipsia) — is caused by excessive drinking due to psychological illness or hypothalamic lesion, with secondary suppression of ADH.
Diagnosis
The cardinal features are polyuria (urine output >3 litres per 24 hours in adults) and polydipsia, with dilute urine (osmolality <300 mOsm/kg) and inappropriately normal or elevated plasma osmolality (>295 mOsm/kg). The water deprivation test (supervised) differentiates DI from primary polydipsia — in true DI, plasma osmolality rises and urine remains dilute. Subsequent desmopressin (synthetic ADH) administration distinguishes cranial DI (urine concentrates markedly) from nephrogenic DI (little or no response). Copeptin measurement (a marker of ADH secretion) offers a more accurate, less cumbersome alternative to the water deprivation test in specialist centres. MRI of the pituitary and hypothalamus is essential in all new cases of cranial DI to identify structural causes.
Management
Cranial DI is treated with desmopressin (DDAVP) — a synthetic analogue of ADH. It is available in intranasal, oral, and subcutaneous/IM/IV formulations. The dose is adjusted individually to control polyuria while avoiding hyponatraemia. Patients must be educated not to drink excessively as this can cause dangerous dilutional hyponatraemia. Nephrogenic DI treatment focuses on removing the causative drug or treating the underlying condition. Thiazide diuretics (bendroflumethiazide) reduce urine volume paradoxically by causing mild volume depletion — this stimulates proximal tubular sodium and water reabsorption, reducing fluid reaching the collecting duct. NSAIDs (indometacin) and amiloride may be added. Adequate hydration must be maintained — fluid intake should match urine output. This article has been prepared following careful evaluation of NICE CKS Diabetes Insipidus, BNF guidance on desmopressin, and Society for Endocrinology guidance.