Diabetes Insipidus (DI)

Diabetes Insipidus (DI)

David Ray Velez, MD

Table of Contents

Definition
Causes
Diagnosis
Treatment

Definition

Definition: Impaired Secretion of or Response to Antidiuretic Hormone (ADH)

Classification

  • Central (Neurogenic) Diabetes Insipidus: Low ADH Secretion
  • Nephrogenic Diabetes Insipidus: Poor Renal Response to ADH

Antidiuretic Hormone (ADH)

  • Also Known As:
    • Vasopressin
    • Arginine Vasopressin (AVP)
  • Production:
    • Produced in Supraoptic and Paraventricular Nuclei of the Hypothalamus
    • Travels Down the Infundibulum and Then Secreted in the Posterior Pituitary
    • Secretion Stimulated by Increased Osmolality and Decreased Arterial Blood Volume
  • Vasopressin Receptors:
    • V-1 Receptor: Arterial Vasoconstriction (Increase Peripheral Vascular Resistance)
    • V-2 Receptor: Renal Water Resorption
    • V-3 Receptor: Mediates Factor VIII and vWF Release

Causes

Causes of Central Diabetes Insipidus

  • Idiopathic – The Most Common Cause of DI Overall
  • Congenital Hypothalamus Malformations
  • Surgery/Neurosurgery
  • Trauma
  • Hypoxic Brain Injury
  • Autoimmune
  • Sarcoidosis
  • Malignancy
  • Anorexia Nervosa

Causes of Nephrogenic Diabetes Insipidus

  • Idiopathic
  • Hereditary (AVPR2 Receptor Mutation)
  • Medications:
    • Lithium
    • Antibiotics
    • Antineoplastic Medications
  • Renal Disease
  • Sickle Cell Disease
  • Pregnancy
  • Electrolyte Disturbances (Hypokalemia and Hypercalcemia)
  • *Most Common Cause of Nephrogenic DI Severe Enough to Produce Polyuria: Chronic Lithium Use or Hypercalcemia

Diagnosis

Generally a Clinical Diagnosis in the Critical Care Setting Based on Presentation and Serum/Urine Labs

Presentation

  • Hypernatremia
  • High Urine Output (> 3 L/Day)
  • Symptoms:
    • Polydipsia
    • Polyuria
    • Nocturia

First Step: Rule Out Hyperglycemia and Other Obvious Osmotic Causes of Polyuria

Laboratory Findings

  • Increased Serum Sodium and Osmolality (> 300 mOsm/kg)
  • Decreased Urine Sodium and Osmolality (< 300 mOsm/kg)

Water Deprivation Test

  • Considered the Gold Standard for Diagnosis of DI but Rarely Performed in the Critical Care Setting (Time Consuming and Many Confounding Variables that Can Make Interpretation Difficult)
  • Test:
    • Water is Deprived for 4-18 Hours with Serial Plasma/Urine Osmolality
      • Dehydration Phase is Stopped Earlier if 3-5% of Body Weight is Lost or Pre-Defined Urine Osmolarity Goals are Seen
    • After Dehydration, 1-2 mcg Desmopressin (DDAVP) are Given
    • Then Then Serum and Urine Osmolality are Measured Every30-60 Minutes for 1-2 Hours
  • Interpretation:
    • Central DI
      • Urine Osmolality < 300 mOsm/kg
      • Urine Osmolality Increases >: 50%
    • Nephrogenic DI
      • Urine Osmolality < 300 mOsm/kg
      • Urine Osmolality Increases < 50%
    • Primary Polydipsia
      • Urine Osmolality Rises to > 300 mOsm/kg

Treatment

Treat Any Underlying Causes

Central Diabetes Insipidus

  • Acute or Severe Symptoms: DDAVP (Desmopressin)
    • Dosing: 1-2 mcg IV Every 12 Hours
  • Mild-Moderate Symptoms: Low-Solute Diet (Low-Sodium and Low-Protein)
    • May Also Consider Thiazide Diuretics

Nephrogenic Diabetes Insipidus

  • Initial Treatment: Low-Solute Diet (Low-Sodium and Low-Protein)
  • If Fails: Thiazide Diuretic (Hydrochlorothiazide)