Diabetic insipidus (DI) is a disorder of water balance characterized by the inability to concentrate urine, resulting in the excretion of large volumes of dilute urine. It is caused by non-osmotic renal loss of water and may lead to dehydration, hypernatremia, and disturbances in fluid and electrolyte balance if untreated. Diabetes insipidus is distinct from diabetes mellitus, as it is not related to abnormalities in blood glucose metabolism but rather to deficiencies in antidiuretic hormone (ADH) secretion or action.

Pathophysiology

Antidiuretic hormone (ADH), also known as arginine vasopressin (AVP), is synthesized in the hypothalamus and released from the posterior pituitary gland. ADH acts on the renal collecting ducts to promote water reabsorption and maintain body water homeostasis. Diabetes insipidus develops when there is inadequate ADH secretion, impaired renal responsiveness to ADH, or excessive water intake that suppresses ADH secretion.

Classification

Central diabetes insipidus

• Caused by complete or partial deficiency of antidiuretic hormone (ADH) secretion from the posterior pituitary gland.

Nephrogenic diabetes insipidus

• Caused by end-organ unresponsiveness of the kidneys to ADH despite normal or elevated hormone levels.

Dipsogenic diabetes insipidus

• Caused by excessive and inappropriate fluid intake due to a defect in the thirst mechanism, resulting in suppression of ADH secretion.

Risk factors

• Head trauma

• Pituitary or hypothalamic surgery

• Pituitary tumors

• Central nervous system infections

• Autoimmune disorders affecting the pituitary or hypothalamus

• Genetic disorders affecting ADH production or renal response

• Chronic kidney disease

• Long-term use of lithium or other nephrotoxic drugs

• Hypercalcemia

• Hypokalemia

Signs and symptoms

Clinical manifestations are primarily related to excessive urinary water loss and compensatory thirst.

Common features include:

• Polyuria, especially nocturnal polyuria

• Polydipsia

• Nocturia

• Passage of large volumes of dilute urine

• Dehydration

• Dry mouth

• Fatigue

• Volume depletion

• Orthostatic hypotension

• Hypernatremia in patients unable to replace water losses

Diagnostic criteria

Diagnosis is suggested by the presence of:

• Polyuria with urine osmolality <300 mOsm/kg for a given plasma osmolality

• Volume depletion and orthostatic hypotension

• Plasma sodium concentration that may be normal or elevated

Investigations

• Urine osmolality

• Plasma osmolality

• Serum sodium concentration

• Serum electrolytes

• Renal function tests

• Water deprivation test when diagnosis is uncertain

• Desmopressin response test to differentiate central from nephrogenic diabetes insipidus

• MRI of the hypothalamic-pituitary region when central diabetes insipidus is suspected

Management

Treatment aims to restore water balance, correct dehydration, treat the underlying cause, and reduce excessive urine output.

Non-pharmacological management

• Replace water deficits promptly according to the degree of dehydration.

• Ensure adequate free water intake to match urinary losses.

• Monitor fluid balance, urine output, serum sodium, and plasma osmolality.

• Identify and treat the underlying cause where possible.

• Educate patients regarding adequate hydration and recognition of dehydration symptoms.

Pharmacological management

Central diabetes insipidus

Desmopressin is the treatment of choice.

• Desmopressin (IV) 2–4 µg/day, divided every 12 hours.

OR

• Desmopressin (PO) initial dose 0.05 mg every 12 hours; effective dose range 0.1–1.2 mg/day, divided every 8–12 hours.

OR

• Desmopressin (intranasal) 10–40 µg (0.1–0.4 mL) once daily, either as a single dose or divided into two or three doses; the usual dose is 20 µg (0.2 mL) daily in two divided doses.

Nephrogenic diabetes insipidus

Treat the underlying cause whenever possible.

Thiazide diuretics may reduce urine volume.

• Bendrofluazide (PO) 5 mg once daily

OR

• Hydrochlorothiazide (PO) 12.5–25 mg once daily.

Prognosis

The prognosis depends on the underlying cause and the type of diabetes insipidus. Central diabetes insipidus usually responds well to desmopressin replacement therapy, allowing most patients to achieve good long-term control of symptoms. Nephrogenic diabetes insipidus may be more difficult to manage but can improve with treatment of the underlying cause, appropriate hydration, and thiazide therapy. Early diagnosis and adequate management help prevent recurrent dehydration, hypernatremia, and associated complications.