Diabetes Insipidus

Overview – Diabetes Insipidus

Diabetes insipidus (DI) is a disorder of impaired water conservation caused by either a deficiency in antidiuretic hormone (ADH) secretion or renal insensitivity to ADH. This results in excessive water loss through dilute urine, leading to intense thirst and high-volume polyuria. Differentiating between neurogenic and nephrogenic causes is critical for appropriate treatment. Though less common than diabetes mellitus, DI can cause significant electrolyte imbalances and requires timely identification.

Definition

Diabetes insipidus is characterised by the inability to concentrate urine due to ADH deficiency or resistance. It leads to excessive thirst (polydipsia) and the excretion of large volumes of dilute urine (polyuria).

Aetiology

Neurogenic (Central) DI

• Deficient secretion of ADH from the posterior pituitary.
• Causes:
  • Idiopathic
  • Head trauma
  • Neurosurgery
  • Brain tumours
  • Infections or inflammation (e.g., meningitis)

Nephrogenic DI

• Normal ADH secretion, but renal collecting ducts are insensitive to its action.
• Causes:
  • Congenital (e.g. AVPR2 gene mutations)
  • Chronic lithium use
  • Hypercalcaemia
  • Hypokalaemia
  • Renal disease

Pathophysiology

• ADH normally promotes water reabsorption in the distal tubules and collecting ducts of the nephron.
• In DI, impaired ADH activity leads to reduced water reabsorption → large volume of hypotonic urine → compensatory polydipsia.
• If water intake is insufficient, hypernatremia and dehydration may result.

Clinical Features

• Polyuria: Excessive dilute urine output
• Polydipsia: Intense thirst
• Nocturia
• Signs of dehydration
• Potential hypokalaemia (especially in nephrogenic DI)

Investigations

Initial Screening

• Normal blood glucose, bicarbonate, and calcium – rules out diabetes mellitus and metabolic causes
• Urinalysis:
  • ↓ Urine osmolality
  • ↓ Specific gravity
  • ↓ Urinary electrolytes

Diagnostic Tests

• Fluid Deprivation Test:
  • Normal response: progressive concentration of urine
  • DI: minimal to no increase in urine osmolality despite dehydration
• Desmopressin Stimulation Test:
  • Neurogenic DI: urine osmolality increases after desmopressin
  • Nephrogenic DI: no change in urine osmolality

Management

General Measures

• Ensure adequate oral hydration
• Monitor serum sodium and osmolality

Neurogenic DI

• Desmopressin (synthetic ADH analogue):
  • Intranasal, oral, or parenteral
  • Reduces urine volume and corrects osmolality

Nephrogenic DI

• Hydrochlorothiazide:
  • Paradoxically reduces urine output by causing mild hypovolemia → increases proximal sodium and water reabsorption
• Low-sodium diet
• NSAIDs (e.g., indomethacin) may reduce urine output in some cases

Complications

• Dehydration
• Hypernatremia
• Hypokalaemia
• Developmental delay (if untreated in children)

Differential Diagnosis

• Diabetes mellitus (check blood glucose)
• Primary polydipsia (psychogenic water drinking)
• Diuretic use
• Hypercalcaemia-induced polyuria
• Chronic kidney disease

Summary – Diabetes Insipidus

Diabetes insipidus is a rare but important condition resulting from reduced ADH activity, either due to impaired secretion (neurogenic DI) or renal resistance (nephrogenic DI). It presents with profound thirst and high-volume dilute urine. Diagnosis relies on urine studies, fluid deprivation, and desmopressin response tests. Management depends on the underlying cause and ranges from desmopressin therapy to thiazide diuretics. For more information, see our Endocrine Overview page.