Diabetes Insipidus

Snapshot

• A 30-year-old woman presents to her primary care physician for increased frequency of urinating, thirst, and urinating at night. She was in a car accident about a month ago, where she had head trauma. Since then, she reports that she has noticed this increased frequency of urination. At that time, head imaging had been normal. Her physician decides to conduct a vasopressin challenge. The results show decreased urine volume and increased urine osmolality. Based on these results, she decides to start the patient on desmopressin. (Central diabetes insipidis)

Introduction

• Clinical definition
  • diabetes insipidus (DI)
    • characterized by excess free water loss and dilute urine

Central vs Nephrogenic Diabetes Inspidus (DI)
	Central DI	Nephrogenic DI
Definition	Failure to produce antidiuretic hormone (ADH)	Insensitivity or resistance of the kidneys to ADH in the collecting duct
Etiology	Pituitary tumor, where vasopressin is released  Other pituitary injuriesautoimmune diseasetrauma surgeryischemia	Drugslithiumdemeclocyclineamphotericin BCongenital (rare)Electrolyte abnormalitieshypercalcemiahypokalemia
Pathogenesis	↓ ADH, resulting in increased extracellular fluid osmolarity	↑ ADH
Vasopressin (DDAVP) challenge	↓ Urine volume and ↑ urine osmolality	No change in urine volume or osmolality

Presentation

• Symptoms
  • polyuria
  • polydipsia
  • nocturia
• thirst

Studies

• Serum labs
  • ↑ serum osmolarity (central DI) 
  • electrolytes
    • hypernatremia
• Other tests
  • 24-hour urine studies
    • best initial test
    • ↓ urine osmolality
    • ↓ urine sodium
    • ↑ urine volume
  • water deprivation challenge
    • no change in urine osmolality or volume
  • vasopressin challenge
    • central DI
      • ↓ urine volume and > 50% ↑ in urine osmolality with DDVAP
    • nephrogenic DI
• lack of response to vasopressin

Differential

• Primary polydipsia 
  • distinguishing factor
    • hyponatremia after trial of desmopressin
• increased urine osmolality with water deprivation test 

Treatment

• Lifestyle
  • hydration
  • low sodium diet
    • nephrogenic DI
• Medical
  • desmopressin (DDAVP)
    • mechanism
      • ADH analog that act on the renal tubular cells to increased water permeability
        • this, in turn, increases water retention
    • indication
      • central DI
  • hydrochlorothiazide
    • mechanism
      • induces mild hypovolemia induces an increase in proximal water and sodium reabsorption
    • indication
      • nephrogenic DI
  • indomethacin
    • mechanism
      • inhibits prostaglandin synthesis
        • prostaglandin synthsis are ADH antagonists
    • indication
      • nephrogenic DI
  • amiloride
    • mechanism
      • epithelial sodium channel inhibitor and is believed to impair lithium entry into the renal pricipal cells
    • indication
• nephrogenic DI secondary to lithium toxicity

 Complications

• Hypernatremia
• Dehydration