Pituitary Apoplexy: Risk Factors and Underlying Molecular Mechanisms

Abstract

Pituitary apoplexy is a rare syndrome, graded from asymptomatic subclinical apoplexy to a life-threatening condition due to pituitary ischemia or haemorrhage of an enlarged pituitary gland. The risk factors and the molecular underlying mechanisms are yet to be elucidated. We provide an overview of the general concepts, the potential factors associated with pituitary adenoma susceptibility for apoplectic events and the molecular mechanisms that could be involved such as HIF-1α/VEGF pathways and metalloproteinases activation, among others. The knowledge of the molecular mechanisms that could participate in the pathogenesis of pituitary apoplexy is crucial to advancement in the identification of future diagnostic tools and therapeutic targets in this rare but sometimes fatal condition.

Keywords: AIP; TNF; VEGF; apoplexy; growth factors; hypoxia-inducing factor; matrix metalloproteinase; molecular; pituitary; review.

Figure 1

Pituitary blood supply and portal system. The adenohypophysis and neuro-hypophysis receive their blood supply primarily from the internal carotid arteries. The infundibulum, the median eminence and the pars tuberalis are supplied by the superior hypophyseal artery (a branch of the internal carotid artery). The posterior pituitary receives its blood supply directly from the inferior hypophyseal artery. The anterior pituitary is supplied indirectly from two sources: (a) Long portal vessels which supply 70% of the blood to the gland and arise from the superior hypophyseal artery; (b) Short portal vessels which supply 30% of blood to the gland and arise from the posterior pituitary. These portal vessels are exquisitely sensitive to volume and pressure changes in the systemic circulation.

Figure 2

Acute pituitary apoplexy. A 40 year-old man, attended to in the emergency room due to sudden onset headache, vomiting and visual symptoms. (A): T1W sagittal view, (B): Fluid attenuated inversion recovery view, (C): T1W coronal view and (D): T2W coronal view. Note the fluid-fluid level within the tumor (yellow arrow).

Figure 3

Predisposing factors and molecular mechanism involved in the pathogenesis of pituitary apoplexy. Some intrinsic characteristics facilitating the apoplectic event (left side). Hypoxia is a plausible molecular trigger of hypoxia-mediated factors, HIF-1α/VEGF and MMP pathways, promoting the tumor growth and angiogenesis, thus making the pituitary tumor prone to apoplectic events (right side).