What is diabetes insipidus and its treatment and laboratory tests?

Diabetes Insipidus: Definition, Diagnosis, and Treatment

Diabetes insipidus (DI) treatment should focus on the specific subtype, with central DI requiring desmopressin replacement therapy and nephrogenic DI requiring thiazide diuretics, low-salt diet, and prostaglandin synthesis inhibitors. 1, 2, 3

Definition and Classification

Diabetes insipidus is an endocrine disorder characterized by:

• Excessive production of dilute urine (polyuria)
• Extreme thirst (polydipsia)
• Preference for cold water

There are four main types:

1. Central DI (Vasopressin Deficiency): Inadequate production/release of antidiuretic hormone (ADH/vasopressin) from the posterior pituitary 4
2. Nephrogenic DI (Vasopressin Resistance): Kidney resistance to ADH action 4
3. Dipsogenic DI: Excessive thirst due to low osmotic threshold 3
4. Gestational DI: Increased placental vasopressinase during pregnancy 3

Diagnostic Approach

Laboratory Tests

• Serum sodium (typically elevated)
• Serum osmolality (typically elevated)
• Urine osmolality (inappropriately low)
• Urine specific gravity (typically low)
• Plasma copeptin levels (newer test)

Functional Tests

1. Water Deprivation Test: Gold standard test to differentiate between central DI, nephrogenic DI, and primary polydipsia 5

   • Measures urine concentration ability when water is withheld
   • Response to desmopressin administration helps differentiate subtypes

2. Hypertonic Saline Infusion Test: Measures copeptin response to osmotic stimulation 4, 5

3. Imaging: MRI of hypothalamic-pituitary region to identify structural causes 5

Treatment Approaches

Central Diabetes Insipidus

• First-line treatment: Desmopressin (synthetic ADH analog) 2, 3

  • Available as nasal spray, oral tablets, or injection
  • Nasal spray (0.01%): Indicated for antidiuretic replacement therapy
  • Dosage individualized based on response
  • Monitor urine volume and osmolality to assess response

• Special considerations:

  • Alternative routes (oral/injectable) needed when nasal route is compromised (nasal congestion, discharge, surgery) 2
  • Fixed desmopressin dosing with minimal breakthrough periods for patients with adipsia 6

Nephrogenic Diabetes Insipidus

• First-line treatment: Thiazide diuretics (e.g., hydrochlorothiazide) 1, 3

  • Can reduce diuresis by up to 50%
  • Enhanced by low-salt diet

• Dietary modifications:

  • Low-salt diet (<6 g/day or 2.4 g sodium)
  • Low-protein diet (<1 g/kg/day)
  • Free access to water at all times

• Additional pharmacological options:

  • NSAIDs (prostaglandin synthesis inhibitors) in combination with thiazides
  • Amiloride for thiazide-induced hypokalemia

Fluid Management

• Intravenous rehydration: 5% dextrose solution (avoid saline) 1
• Rate calculation:
  • Adults: 25-30 ml/kg/24h
  • Children (first 10 kg): 100 ml/kg/24h
  • Children (10-20 kg): 50 ml/kg/24h
  • Children (remaining): 20 ml/kg/24h

Monitoring and Follow-up

• Regular monitoring of serum electrolytes, renal function
• Urine osmolality and 24-hour volume measurements
• Ultrasound of urinary tract every 2-3 years for nephrogenic DI
• Blood tests every 3-12 months (more frequent in children)

Potential Complications

• Osmotic demyelination syndrome: Can occur with rapid correction of hypernatremia
  • Prevent by limiting sodium decrease to <8 mmol/L/day 1
• Urinary tract dilatation: Can lead to "flow uropathy" and increased risk of chronic kidney disease
• Growth and development issues: Can occur in children with DI

Special Situations

• Surgical procedures: Require close monitoring of fluid balance and electrolytes
• Pregnancy: Prostaglandin synthesis inhibitors should be discontinued
• Adipsic DI: Requires fixed desmopressin dosing with scheduled fluid replacement 6

Common Pitfalls

• Confusing diabetes insipidus with diabetes mellitus (completely different pathophysiology)
• Failing to differentiate between central and nephrogenic DI before initiating treatment
• Rapid correction of hypernatremia leading to osmotic demyelination syndrome
• Inadequate monitoring of electrolytes during treatment