Central Diabetes Insipidus

Aka: Central Diabetes Insipidus, Central DI

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II. Pathophysiology

  1. Mechanism
    1. Antidiuretic Hormone (ADH) deficiency
      1. Contrast with Nephrogenic Diabetes Insipidus (deficient renal response to ADH)
  2. Polyuria
    1. Decreased ADH release
  3. Permanent Polyuria
    1. Central lesion above median eminence
  4. Transient Polyuria
    1. Central lesion below median eminence
    2. ADH passes via Hypothalamus to portal capillaries
    3. Results in ADH release below the median eminence

III. Etiology

  1. Idiopathic (30%)
    1. Autoimmune Disease (common)
      1. Lymphocyte inflammation
        1. Pituitary stalk (thickened stalk on MRI)
        2. Posterior pituitary
      2. Anterior Pituitary deficiency
        1. Growth Hormone
        2. ACTH deficient
    2. Familial Diabetes Insipidus (very rare)
      1. Point mutation in ADH precursor gene
        1. Precursor accumulates
        2. Toxicity to ADH synthesizing cells
      2. Enhancement within Hypothalamus on MRI
  2. Severe Traumatic Brain Injury
    1. Hypothalamus or pituitary injury
  3. Neurosurgery (Transsphenoidal)
    1. Results from Hypothalamus or Pituitary Trauma
    2. Most common cause of Polyuria post neurosurgery
    3. Differential Diagnosis
      1. Excess fluids
      2. Mannitol
      3. Corticosteroids
    4. Approach
      1. Check Urine Osmolality
      2. Observe response to water restriction
  4. Malignancy
    1. Examples: Lung Cancer, Leukemia, Lymphoma
    2. Polyuria may be presenting symptom
  5. Langerhans Histiocytosis (Histiocytosis X)
    1. Infiltrative disease
    2. Sarcoidosis causes similar infiltration
  6. Post SVT resolution
  7. Anorexia Nervosa
  8. Pregnancy exacerbates any of above forms

IV. Diagnosis

  1. Fluid Deprivation Test
    1. No response to water deprivation
    2. Response to exogenous ADH administration
  2. Hare-Hickey Test
    1. Decreased ADH to Serum Osmolality ratio

V. Radiology: MRI Head

  1. Central DI: Diminished signal at posterior pituitary

VI. Management

  1. General Measures that potentiate ADH
    1. Low Sodium Diet
    2. NSAIDs
  2. dDAVP (Desmopressin)
    1. Synthetic ADH replacement Hormone
    2. dDAVP 10 to 20 ug bid intranasally
  3. Chlorpropamide 125-250 mg PO qd-bid
    1. Antidiuretic effect - may lower Urine Output by 50%
    2. Risk of Hypoglycemia at higher doses
  4. Carbamazepine 100-300 mg bid
    1. Enhances ADH response
    2. May lower Urine Output by 50%
  5. Hydrochlorothiazide with low salt intake
    1. Decreases Polyuria
    2. Dose: 25 mg qd to bid

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