Pathophysiology of hypopituitarism in the setting of brain injury

Abstract

The complex pathophysiology of traumatic brain injury (TBI) involves not only the primary mechanical event but also secondary insults such as hypotension, hypoxia, raised intracranial pressure and changes in cerebral blood flow and metabolism. It is increasingly evident that these initial insults as well as transient events and treatments during the early injury phase can impact hypothalamic-pituitary function both acutely and chronically after injury. In turn, untreated pituitary hormonal dysfunction itself can further hinder recovery from brain injury. Secondary adrenal insufficiency, although typically reversible, occurs in up to 50% of intubated TBI victims and is associated with lower systemic blood pressure. Chronic anterior hypopituitarism, although reversible in some patients, persists in 25-40% of moderate and severe TBI survivors and likely contributes to long-term neurobehavioral and quality of life impairment. While the rates and risk factors of acute and chronic pituitary dysfunction have been documented for moderate and severe TBI victims in numerous recent studies, the pathophysiology remains ill-defined. Herein we discuss the hypotheses and available data concerning hypothalamic-pituitary vulnerability in the setting of head injury. Four possible pathophysiological mechanisms are considered: (1) the primary brain injury event, (2) secondary brain insults, (3) the stress of critical illness and (4) medication effects. Although each of these factors appears to be important in determining which hormonal axes are affected, the severity of dysfunction, their time course and possible reversibility, this process remains incompletely understood.

Fig. 1

Illustration demonstrating the anatomy and blood supply of the hypothalamic-pituitary axis. Note that the superior hypophyseal artery and long hypophyseal portal vessels arise above the diaphragma sella which may make them vulnerable to intracranial injury including shearing forces as well as compression by raised intracranial pressure, brain swelling, and brain shift. (Abbreviations: cICA, cavernous internal carotid artery; DS, diaphragma sella; I, infundibulum; IHA, inferior hypophyseal artery; LHV, long hypophyseal portal vessels; OC, optic chiasm; P, pituitary gland; SHA, superior hypophyseal artery; SHV, short hypophyseal portal vessels)

Fig. 2

Pituitary pathology after fatal head injury demonstrating infarction of the peripheral regions of the anterior pituitary gland in the long hypophyseal vein distributions. Note that the central areas in the distribution of the short hypophyseal vessels are relatively preserved. From Daniel et al. [62]