Last reviewed: July 2020
Last updated: March  2020



History and exam

Key diagnostic factors

  • history of pituitary/hypothalamic disease
  • family history/genetic mutations
  • history of lithium therapy
  • history of autoimmune disorders
  • polyuria
  • increased thirst/polydipsia

Other diagnostic factors

  • nocturia
  • signs of volume depletion
  • non-specific central nervous system symptoms of hypernatraemia
  • visual field defects
  • focal motor deficits
  • sensorineural deafness and visual failure
  • skin lesions

Risk factors

  • pituitary surgery
  • craniopharyngioma
  • pituitary stalk lesions
  • traumatic brain injury
  • congenital pituitary abnormalities
  • medication
  • autoimmune disease
  • family history/genetic mutations
  • pregnancy
  • subarachnoid haemorrhage
  • renal sarcoidosis
  • renal amyloidosis
  • hypercalcaemia or hypokalaemia
  • release of obstructive uropathy
  • previous central nervous system infections

Diagnostic investigations

1st investigations to order

  • urine osmolality
  • serum osmolality
  • serum glucose
  • serum sodium
  • serum potassium
  • serum urea nitrogen
  • serum calcium
  • urine dipstick
  • 24-hour urine collection for volume
  • water deprivation test
  • AVP (desmopressin) stimulation test
  • hypertonic saline-stimulated test with measurement of copeptin
More 1st investigations to order

Investigations to consider

  • cranial MRI (contrast-enhanced)
  • genetic testing
  • antithyroid peroxidase autoantibodies
  • serum and cerebrospinal fluid alpha-fetoprotein and beta-human chorionic gonadotrophin
  • serum growth hormone (GH)
  • serum insulin-like growth factor 1 (IGF-1)
  • provocative growth hormone (GH) tests
  • serum LH
  • serum follicle-stimulating hormone
  • morning serum testosterone
  • serum thyroid-stimulating hormone and triiodothyronine/thyroxine (T3/T4)
  • morning serum cortisol and adrenocorticotrophic hormone (ACTH)
  • serum prolactin
More investigations to consider

Treatment algorithm


Consultant Endocrinologist

Manchester University Foundation Trust

Hon. Professor of Medicine and Endocrinology

Manchester Academic Health Science Centre




SB declares that he has no competing interests.

Dr Stephen Ball wishes to gratefully acknowledge Dr Mark Sherlock and Dr Paul M. Stewart, previous contributors to this topic.

Peer reviewersVIEW ALL

Professor of Medicine

Division of Endocrinology and Metabolism

University of Pittsburgh School of Medicine




At the time of peer review, JA received research grants from the National Institutes of Health, the Department of Veterans' Affairs, and the Department of Defense. We were made aware that Professor Amico is now deceased.

Professor of Endocrinology

Department of Endocrinology

Beaumont Hospital




CT declares that he has no competing interests.

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