Hypothalamic-Pituitary Function in Brain Death: A Review

J Intensive Care Med. 2016 Jan;31(1):41-50. doi: 10.1177/0885066614527410. Epub 2014 Mar 31.


The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.

Keywords: Uniform Determination of Death Act; brain death; diabetes insipidus; hypothalamus; pituitary.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain Damage, Chronic / pathology*
  • Brain Damage, Chronic / physiopathology*
  • Brain Death / pathology
  • Brain Death / physiopathology*
  • Corticotropin-Releasing Hormone / blood
  • Gonadotropin-Releasing Hormone / blood
  • Growth Hormone-Releasing Hormone / blood
  • Humans
  • Hypothalamic Hormones / blood*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Hypothalamus / pathology*
  • Life Support Care
  • Pituitary Gland / pathology*
  • Pituitary Hormones / blood*


  • Hypothalamic Hormones
  • Pituitary Hormones
  • Gonadotropin-Releasing Hormone
  • Corticotropin-Releasing Hormone
  • Growth Hormone-Releasing Hormone