Pituitary Apoplexy and the Diagnosis of Brain Death

10.1055/s-0045-1803926

Brain death (BD) is defined as the irreversible cessation of all brain functions, including those of the brainstem. However, reports of preserved pituitary–hypothalamic function in brain-dead patients challenge the comprehensiveness of this definition. Mattheisen et al described a case of pituitary apoplexy, which led to massive bilateral ICA territory stroke, rapid neurological deterioration, and eventual BD diagnosis. This case underscores the complexity of BD/DNC (death by neurological criteria) determination, particularly regarding the hypothalamic–pituitary axis.

Despite severe cerebral ischemia, the pituitary–hypothalamic region may retain function due to its dual blood supply from both the internal and external carotid arteries. The internal carotid artery supplies the anterior pituitary and hypothalamus, while the external carotid artery, via the inferior hypophyseal arteries, maintains the posterior pituitary's function. This vascular resilience allows for ongoing endocrine activity, including hormone secretion, pituitary responsiveness, and osmoregulation, in some brain-dead patients.

This case highlights the need to reconsider BD/DNC criteria in light of persisting neuroendocrine function. The findings suggest that the persistence of pituitary activity may necessitate further physiological and ethical discussions regarding the validity of BD as an absolute cessation of brain function.

Mattheisen et al reported an unusual case of pituitary apoplexy, which caused immediate vision loss and a rapid decline in neurological function due to massive bilateral ICA territory stroke.[1] This case highlights an essential aspect of the diagnosis of BD/DNC.[2]

According to the Uniform Determination of Death Act (UDDA), an individual is declared dead when “all functions of the entire brain” have irreversibly ceased.[3] [4] However, the persistence of certain hypothalamic functions, including the secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a significant proportion of patients who are diagnosed as brain dead, raises questions about the comprehensiveness of this definition.[3] [4] [5]

The apparent paradox of residual pituitary–hypothalamic function in brain-dead patients—despite global intracranial circulatory arrest—can be clarified by distinguishing between intracranial cerebrovascular regulation and regions outside the blood–brain barrier (BBB). The posterior pituitary (neurohypophysis), located in the sella turcica and partially external to the dura mater and BBB, receives its blood supply from the inferior hypophyseal arteries, which stem from the cavernous segment of the internal carotid artery—a region that remains extracranial and extracerebral. Thus, even in the absence of intracranial cerebral blood flow, this area may maintain perfusion and secrete antidiuretic hormone (ADH) for a limited period. In addition, residual endocrine activity—particularly during the second phase of triphasic diabetes insipidus observed in pituitary macroadenomas—can be explained by the release of stored hormones from dying pituitary cells, a phenomenon akin to pituitary apoplexy. This cell death–induced hormone surge may transiently mimic preserved pituitary function in brain-dead patients. Furthermore, preserved perfusion pressure in the extracranial carotid arteries may support this endocrine residual function, though it does not imply continued hypothalamic regulatory control. These anatomical and physiological nuances reinforce the distinction between endocrine residue and true brain activity, aligning with the definition of BD while acknowledging the need for precise terminology in evaluating hypothalamic–pituitary dynamics.[5]

Mattheisen et al described MRI findings showing extensive bilateral infarcts in the MCA and ACA distributions, ultimately leading to BD after 2 days. This case underscores the complexity of BD/DNC diagnosis and the potential persistence of pituitary–hypothalamic function in such patients.[3]

Publication History

Article published online:
30 October 2025

• References

• 1 Mattheisen H, Peterson A, Cheok S, Zwagerman N. Pituitary apoplexy resulting in massive bilateral strokes and brain death. J Neurol Surg B Skull Base 2025; 86 (S 01): S1-S576
• 2 Nair-Collins M. Must hypothalamic neurosecretory function cease for brain death determination?. Yes: UDDA Revision Series. Neurology 2023; 101 (03) 134-136
• 3 Machado C. Reader response: challenges to brain death in revising the uniform determination of death act: the UDDA Revision Series. Neurology 2024; 102 (01) e208044
• 4 Varelas PN, Kananeh M, Brady P. et al. The relationship between manifestation of diabetes insipidus and estimated glomerular filtration rate in brain death. Crit Care Med 2024; 52 (02) e58-e66
• 5 Rhoton Jr AL. The sellar region. Neurosurgery 2002; 51 (4, Suppl): S335-S374