DIABETES INSIPIDUS


I. Pathophysiology
  1. Interstitial fluid in the kidney is hypertonic, allowing free water to return to systemic circulation
  2. Antidiuretic hormone (ADH, aka arginine vasopressin or AVP) acts on cortical and medullary collecting tubules to alter their permeability to water
  3. There are two ADH receptor types:
    1. V1-Affects corticotrophin release, synthesis of prostaglandins, and vasoconstriction
    2. V2-Mediates antidiuretic response
II. Classification
  1. "Central" DI-Caused by deficiency in ADH
    1. Primary (no identifiable pituitary or hypthalamic lesion)
    2. Secondary (due to known damage to pituitary or hypothalamus, e.g. tumor, infection, sarcoidosis, or instrumentation or other trauma; 10-20% of patients who have transsphenoidal resection of a pituitary adenoma develop central DI)
  2. "Peripheral" aka "Nephrogenic" DI-Caused by peripheral resistance to ADH in the renal tubules
    1. Congenital (rare; 90% of cases result from an X-linked defect in gene for the AVP receptor 2; also an autosomal-dominant form is caused by a mutation in aquaporin gene, AQP2)
    2. Acquired, e.g. in association with:
      1. Sjogren's syndrome
      2. Pyelonephritis
      3. Myeloma
      4. Chronic hypercalcemia
      5. Sickle cell anemia
      6. Certain medications e.g. lithium
  3. Gestational DI-Very rare; Caused by peripheral destruction of ADH
III. Clinical features and epidemiology
  1. Male:Female about 1:1
  2. Excessive thirst
  3. Polyuria
  4. Signs of volume depletion
  5. Urine specific gravity (usually < 1.005) inappropriately low for the degree of volume depletion present
  6. Absence of severe hyperglycemia
  7. Hypernatremia typically present
IV. Management
  1. Check renal function and blood glucose (the latter to rule out uncontrolled diabetes mellitus as cause of polyuria, polydipsia, and volume depletion)
  2. MRI of pituitary and hypothalamus if suspect central DI
  3. Can confirm central DI by administering exogenous ADH and monitoring urine volume and serum electrolytes (will improve if cause of DI is central)
  4. Central and gestational DI are  treated with DDAVP (synthetic ADH), typically intranasally
  5. Nephrogenic DI is treated with low sodium/low protein diet
  6. Both central and peripheral DI may improve with hydrochlorothiazide
  7. Indomethacin and DDAVP may help in resistant peripheral DI
(Sources include Core Content Review in Family Medicine, 2012)