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For further information, see CMDT Part 26-02: Central Diabetes Insipidus

Key Features

Essentials of Diagnosis

  • Antidiuretic hormone (ADH) deficiency causes central diabetes insipidus (DI) with polyuria (2–20 L/day) and polydipsia

  • Hypernatremia occurs if fluid intake is inadequate

General Considerations

  • DI is an uncommon disease caused by a deficiency of or resistance to ADH, also known as vasopressin

  • Reversible central diabetes insipidus can occur

    • With administration of ketamine or temozolomide

    • In the myelodysplastic preleukemic phase of acute myelogenous leukemia

Deficiency of vasopressin (central DI)

  • Primary

    • No lesion on MRI of pituitary and hypothalamus

    • May be familial or idiopathic

  • Secondary to damage to hypothalamus or pituitary stalk by

    • Tumor

    • Hypophysitis

    • Infarction

    • Hemorrhage

    • Anoxic encephalopathy

    • Surgical or accidental trauma

    • Infection (eg, encephalitis, tuberculosis, syphilis)

    • Granulomas (sarcoidosis or Langerhans cell granulomatosis)

  • Avelumab (an anti-PD-L1 monoclonal antibody) can cause reversible central diabetes insipidus

  • Metastases to pituitary cause DI more often than do pituitary adenomas (33% vs. 1%)

Resistance to vasopressin ("nephrogenic" DI)

  • Caused by unresponsiveness of the kidney tubules to the normal secretion of vasopressin

  • Polyuria is unresponsive to vasopressin although patients have normal vasopressin secretion

  • Congenital nephrogenic DI is

    • X-linked

    • Present from birth

    • Due to defective expression of renal vasopressin V2 receptors or vasopressin-sensitive water channels

  • Acquired form is less severe and is seen in

    • Pyelonephritis

    • Renal amyloidosis

    • Plasma cell myeloma

    • Hypokalemia

    • Sjögren syndrome

    • Sickle cell anemia

    • Hypercalcemia

    • Recovery from acute tubular necrosis

  • Nephrogenic DI may also be caused by drugs

    • Corticosteroids

    • Diuretics

    • Demeclocycline

    • Tetracycline

    • Lithium

    • Foscarnet

    • Methicillin


  • In familial autosomal dominant central DI, symptoms begin at about age 2 years

Clinical Findings

Symptoms and Signs

  • Intense thirst, especially for ice water

  • Polyuria

  • 2 L to 20 L of fluid ingested daily, with corresponding urine volumes

  • Although most patients maintain fluid balance, dehydration and hypernatremia occur if patients are unable to drink (eg, comatose) or if hypothalamic thirst center is damaged (eg, by shock, anoxia, or tumor)

  • Partial DI presents with less intense symptoms and should be suspected in unremitting enuresis

  • Wolfram syndrome

    • DI can occur in this rare, autosomal-recessive disorder

    • Also known by the acronym DIDMOAD (diabetes insipidus, type 1 diabetes mellitus, optic atrophy, and deafness)

    • Manifestations usually present in childhood but may not occur until adulthood, along with depression and cognitive problems

Differential Diagnosis

  • Polyuria caused by

    • Psychogenic polydipsia

    • Diabetes mellitus

    • Cushing syndrome

    • Hypercalcemia

    • Hypokalemia

    • Parkinson disease


Laboratory Tests

  • 24-h urine collection for volume (< 2 L/day rules out DI), creatinine (to ensure accurate collection and assess creatinine clearance)

  • Serum for osmolality, glucose, potassium (hypokalemia causes polyuria), sodium, ...

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