Diabetes Insipidus

KEY FEATURES

Essentials of Diagnosis

• Antidiuretic hormone (ADH) deficiency causes central diabetes insipidus (DI) with polyuria (2–20 L/d) 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, from the posterior pituitary

• Primary central DI

  • No lesion on MRI of pituitary and hypothalamus

  • Accounts for about one-third of cases of DI

  • May be familial, idiopathic, or due to autoimmunity

  • Reversible central diabetes insipidus can occur

    • With administration of ketamine, temozolomide, or the anti PD-L1 monoclonal antibody avelumab

    • In the myelodysplastic preleukemic phase of acute myelogenous leukemia

• Secondary central DI

  • Most commonly due to damage to hypothalamus or pituitary stalk by

    • Tumor

    • Hypophysitis

    • Infarction

    • Hemorrhage

    • Anoxic encephalopathy

    • Traumatic brain injury

    • Surgery involving the pituitary or hypothalamus

  • Adipsic central diabetes insipidus

    • Damage to the anterior hypothalamic thirst center

    • Commonly occurs after neurosurgical clipping of an anterior communicating artery aneurysm

  • Other causes

    • Infection (eg, encephalitis, tuberculosis, syphilis)

    • Craniopharyngioma

    • Germinoma

    • Granulomas (sarcoidosis or Langerhans cell granulomatosis)

• Metastases to the pituitary or infundibulum cause DI more often than do pituitary adenomas (33% versus 1%)

• Nephrogenic DI

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

  • Congenital nephrogenic DI is

    • Familial, X-linked

    • 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

    • Chronic hypercalcemia

    • Recovery from acute tubular necrosis

  • Nephrogenic DI may also be induced by drugs

    • Corticosteroids

    • Diuretics

    • Demeclocycline

    • Lithium

    • Foscarnet

    • Methicillin

• Vasopressinase-induced DI

  • Associated with oligohydramnios, preeclampsia, or liver dysfunction, and in the puerperium

  • Maternal circulating vasopressin is destroyed by placental vasopressinase; synthetic desmopressin is unaffected

Demographics

• 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

• Most patients maintain fluid balance

• However, dehydration and hypernatremia occur if patients do not have free access to water or if the anterior hypothalamic thirst center is damaged

• 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

  • Nocturnal polyuria of Parkinson disease

DIAGNOSIS