Reply to: Pituitary Apoplexy and the Diagnosis of Brain Death

10.1055/a-2689-2913

We thank Dr. Machado et al[1] for their thoughtful response to our report on a neurologically devastating case of pituitary apoplexy. Our manuscript detailed an unusual presentation in which pituitary apoplexy resulted in massive bilateral ICA territory infarctions, ultimately ending in patient demise. Strokes secondary to pituitary apoplexies are rare, with only a few cases reported in the literature. Machado et al highlight the important role of hypothalamic-pituitary function in the broader discussion of brain death (BD) and death by neurologic criteria (DNC).

The Uniform Determination of Death Act (UDDA) classifies the death of an individual who has sustained either irreversible cessation of circulatory and respiratory functions, or irreversible cessation of the entire brain, including the brain stem. However, there are discrepancies in the standard tests for clinically determining neurologic death, as these may not account for the entire brain function.[2] [3] After neurological death, the human body can maintain its ability for metabolic function and homeostasis.[4] This phenomenon raises important physiological and ethical considerations for the definition of BD as the irreversible cessation of “all functions of the entire brain,” and as highlighted by Dr. Machado. Evidence has shown that with the unique dual vascular supply of the pituitary-hypothalamic axis, residual neuroendocrine activity can persist despite catastrophic cerebral injury. Previous studies have shown the persistence of hypothalamic-pituitary activity in some patients who otherwise fulfilled clinical criteria for BD/DNC. In their review of 1,800 patients declared brain dead, Nair-Collins et al found that half did not develop diabetes insipidus, indicating at least partially preserved neuroendocrine function via vasopressin secretion and osmoregulation. In some cases, the anterior pituitary remained responsive to stimulation, and hormones such as TSH, ACTH, and GH were detectable.[2] [5]

The comprehensive definition and classification of BD warrant further discussion. The current definition of BD given by the UDDA leaves room for various interpretations of what classifies “entire BD.” The argument of how to classify residual biochemical and cellular homeostasis after neurological death remains heavily debated. Nair-Collins et al argue that since the hypothalamic-pituitary axis is part of the brain, ancillary testing for declaring BD should therefore include tests that test its function.[2] [5]On the contrary, Machado et al emphasize an important point that the dual blood supply of the hypothalamic-pituitary axis stimulates a hormone surge even after neurologic death, which could be interpreted as preserved brain function.

We agree with Machado et al that the continued presence of neuroendocrine function in brain-dead patients should not be interpreted as evidence of global brain viability, but rather as a reflection of the unique vascular supply of the hypothalamic-pituitary axis. We are grateful that our case has contributed to this important dialogue regarding the definition and classification of BD/DNC. Finally, we echo Machado et al's call for continued discussion of a definition that integrates clinical, anatomical, and ethical perspectives in shaping the criteria for refining the criteria for BD/DNC. Refining the criteria for BD/DNC should clearly define the role of neuroendocrine function in BD and provide clear guidelines for testing of hypothalamic-pituitary function, if so. It is critical to maintain precision and reproducibility in medical decision-making regarding BD/DNC determination.

Publication History

Received: 25 October 2025

Accepted: 16 December 2025

Article published online:
09 January 2026

• References

• 1 Machado C, Sanchez JJ, Saniova B, Drobný M, Schift A. Pituitary apoplexy and the diagnosis of brain death. . J Neurol Surg B Skull Base Published online October 30, 2025
• 2 Nair-Collins M, Miller FG. Current practice diagnosing brain death is not consistent with legal statutes requiring the absence of all brain function. J Intensive Care Med 2022; 37 (02) 153-156
• 3 Biel S, Durrant J. Controversies in brain death declaration: legal and ethical implications in the ICU. Curr Treat Options Neurol 2020; 22 (04) 12
• 4 Aboubakr M, Yousaf MIK, Weisbrod LJ, Alameda G. Brain Death Criteria (Archived). In: StatPearls. Treasure Island (FL): StatPearls Published online; ; January 31, 2024
• 5 Nair-Collins M, Northrup J, Olcese J. Hypothalamic-pituitary function in brain death: a review. J Intensive Care Med 2016; 31 (01) 41-50