What are the diagnostic steps and treatment options for diabetes insipidus?

Diagnostic Approach for Diabetes Insipidus

The diagnosis of diabetes insipidus requires a systematic approach starting with clinical suspicion based on polyuria and polydipsia, followed by laboratory evaluation of serum and urine osmolality, and confirmatory testing with either water deprivation or hypertonic saline stimulation tests. 1, 2

Clinical Presentation and Initial Evaluation

• Suspect diabetes insipidus in children presenting with polyuria, polydipsia, failure to thrive, and hypernatremic dehydration with inappropriately low urine osmolality (typically <200 mOsm/kg H₂O) 1
• In adults, unexplained polydipsia and polyuria should raise suspicion for diabetes insipidus 1
• Initial laboratory evaluation should include measurement of serum sodium, serum osmolality, and urine osmolality 1, 2
• Detection of inappropriately diluted urine combined with high-normal or elevated serum sodium is pathognomonic for diabetes insipidus 3

Diagnostic Testing

Imaging

• MRI with and without IV contrast using high-resolution pituitary or skull base protocols is the preferred initial imaging modality for suspected central diabetes insipidus 2, 3
• Thin-section T1-weighted images are crucial to identify the typical T1 signal hyperintensity of normal neurosecretory granules; absence of this signal may indicate central diabetes insipidus 2
• CT with IV contrast can be considered in emergency settings but is less sensitive than MRI 2

Functional Testing

• The DDAVP challenge test helps distinguish central from nephrogenic diabetes insipidus 2, 3
  • In central diabetes insipidus: Administration of desmopressin results in increased urine osmolality and decreased urine volume 3
  • In nephrogenic diabetes insipidus: No significant change in urine concentration occurs after desmopressin administration 3
• Water deprivation test followed by desmopressin administration remains the gold standard for diagnosis 4
• Plasma copeptin measurement is emerging as a promising biomarker that may simplify and improve diagnostic accuracy 4, 5

Genetic Testing

• Early genetic testing is recommended in patients with clinical symptoms of suspected nephrogenic diabetes insipidus 1
• Genetic testing of AVPR2 and AQP2 is recommended in all symptomatic females 1
• Genetic testing using umbilical cord blood is recommended in male offspring of known heterozygote female carriers of AVPR2 mutations 1
• Genetic testing should be performed in laboratories accredited for diagnostic genetic testing 1

Differential Diagnosis

• Four main entities must be differentiated 6:
  • Central diabetes insipidus: deficiency of arginine vasopressin (AVP) in the pituitary or hypothalamus
  • Nephrogenic diabetes insipidus: resistance to AVP in the kidneys
  • Gestational diabetes insipidus: increase in placental vasopressinase
  • Primary polydipsia: excessive water intake despite normal AVP secretion and action

Treatment Approaches

Central Diabetes Insipidus

• Desmopressin nasal spray is indicated as antidiuretic replacement therapy for central cranial diabetes insipidus 7
• It is also indicated for management of temporary polyuria and polydipsia following head trauma or surgery in the pituitary region 7
• Desmopressin treatment results in reduction of urinary output with increased urine osmolality and decreased plasma osmolality 7
• Some patients may show decreased responsiveness or shortened duration of effect over time (usually >6 months) 7

Nephrogenic Diabetes Insipidus

• Desmopressin is ineffective for nephrogenic diabetes insipidus 7
• Treatment includes dietary modifications to decrease renal osmotic load 1
• In symptomatic infants and children, thiazide diuretics combined with prostaglandin synthesis inhibitors are recommended 1
• Thiazides act by inducing mild volume depletion and can reduce diuresis by up to 50% in the short term when combined with a low-salt diet 1
• For thiazide-induced hypokalemia, addition of amiloride is recommended 1

Special Considerations

• Close monitoring of fluid balance, weight, and biochemistry is essential when starting treatment for nephrogenic diabetes insipidus 1
• For patients with central diabetes insipidus where the intranasal route may be compromised (nasal congestion, discharge, atrophy, severe rhinitis), desmopressin solution for injection is available 7
• Patients with idiopathic central diabetes insipidus require close follow-up as it can be the first sign of an underlying pathology 6
• Regular control of blood glucose is recommended when using intravenous glucose solutions in patients with diabetes insipidus 1