Diabetes insipidus (DI) is a disorder characterized by impaired water reabsorption in the kidneys, leading to excessive polyuria and polydipsia. It is essential for the UKMLA, highlighting its types, causes, clinical features, investigations, and management.

Key Features:

1. Polyuria: High urine output (>3 liters/day in adults).
2. Polydipsia: Excessive thirst, craving for cold water.
3. Nocturia: Frequent nighttime urination.
4. Dehydration Symptoms: If water intake is insufficient.

Types of Diabetes Insipidus:

1. Central DI (Neurogenic):
   • Insufficient secretion of antidiuretic hormone (ADH) by the posterior pituitary.
2. Nephrogenic DI:
   • Renal insensitivity to ADH action despite normal secretion.
3. Primary Polydipsia (not true DI):
   • Excessive water intake due to psychological or habitual causes.

Causes:

1. Central DI:

1. • Idiopathic (most common).
   • Trauma: Head injury or neurosurgery.
   • Tumours: Craniopharyngioma, pituitary adenomas.
   • Infections: Meningitis, encephalitis.
   • Vascular: Sheehan syndrome, pituitary apoplexy.

2. Nephrogenic DI:

1. • Congenital: Mutations in AVPR2 or AQP2 genes.
   • Drugs: Lithium, demeclocycline.
   • Electrolyte disturbances: Hypercalcemia, hypokalaemia.
   • Renal diseases: Chronic kidney disease (CKD), polycystic kidney disease.
   • Metabolic disorders: Amyloidosis, sarcoidosis.

Pathophysiology:

• Central DI: Reduced ADH secretion → decreased water reabsorption in collecting ducts → large volume of dilute urine.
• Nephrogenic DI: Renal resistance to ADH → impaired water reabsorption → polyuria.

Clinical Presentation:

1. Classic Symptoms:
   • Persistent polyuria and polydipsia.
   • Nocturia.
2. Signs of Dehydration (if water intake is restricted):
   • Dry mucous membranes.
   • Hypotension and tachycardia.
   • Hypernatremia symptoms (confusion, lethargy, seizures).

Investigations:

1. Initial Tests:

1. • Serum Sodium: Elevated in dehydration or inadequate water intake.
   • Serum Osmolality: Increased (>295 mOsm/kg) in DI.
   • Urine Osmolality: Decreased (<300 mOsm/kg) in DI.
   • Urine Specific Gravity: Low (<1.005).

2. Water Deprivation Test:

1. • Monitors urine osmolality and volume after fluid restriction.
   • Differentiates primary polydipsia, central DI, and nephrogenic DI.
   • In central DI: Urine osmolality remains low and increases significantly (>50%) after ADH (desmopressin) administration.
   • In nephrogenic DI: No response to ADH.

3. Plasma ADH Levels:

1. • Low in central DI.
   • Normal/high in nephrogenic DI.

4. Imaging:

1. • MRI of the brain: Assess hypothalamic-pituitary axis for tumours, trauma, or structural abnormalities.

Management:

1. General Measures:

1. • Adequate water intake to prevent dehydration.
   • Monitor serum sodium and osmolality.

2. Central DI:

1. • Desmopressin (DDAVP):
     • Synthetic ADH analog.
     • Administered intranasally, orally, or subcutaneously.
   • Treat underlying cause (e.g., surgery for tumours).

3. Nephrogenic DI:

1. • Treat underlying cause (e.g., discontinue nephrotoxic drugs like lithium).
   • Thiazide Diuretics:
     • Paradoxically reduce urine output by inducing mild hypovolemia and increasing proximal tubular water reabsorption.
   • Low-Sodium Diet:
     • Reduces urinary water loss.
   • NSAIDs (e.g., indomethacin):
     • Enhance renal response to ADH.

4. Primary Polydipsia:

1. • Behavioural therapy.
   • Reduce water intake gradually.

Complications:

1. Severe Dehydration: If water intake is insufficient.
2. Hypernatremia: Can lead to neurological symptoms (seizures, confusion, coma).
3. Hypokalaemia: From nephrogenic DI if on chronic thiazides.

Differentiating DI from Other Conditions:

• Diabetes Mellitus: Polyuria + polydipsia with glucosuria and high plasma glucose.
• Psychogenic Polydipsia: Polyuria with normal urine osmolality after water deprivation.

Key Exam Points for UKMLA:

• Water Deprivation Test: Critical for diagnosis and differentiation.
• Desmopressin Response: Key to distinguishing central vs. nephrogenic DI.
• Common Causes:
  • Central: Trauma, surgery, idiopathic.
  • Nephrogenic: Lithium, hypercalcemia.
• Complication Awareness: Hypernatremia and dehydration.