Metabolism modulators in sepsis: the abnormal pituitary response

Abstract

Objective: Summarize the current knowledge on the role of the hypothalamic pituitary axis in the development of sepsis.

Design: Review article.

Method: We systematically searched for relevant articles in MEDLINE and Embase (up to December 2006) using the following search terms: sepsis or septic shock or septicemia or endotoxemia and pituitary gland or hypothalamus. We also retrieved relevant references from selected articles.

Results: During sepsis, the pituitary gland is activated via blood-borne proinflammatory cytokines and through a complex interaction between the autonomic nervous system and the immune cells. Sepsis elicits a very reproducible pattern of pituitary hormone secretion, with plasma adrenocorticotropin and prolactin increasing within a few minutes following the insult, and with a rapid inhibition of secretion of luteinizing and thyroid-stimulatory hormone but not of follicle-stimulating hormone. Growth hormone secretion also is stimulated. Nitric oxide is a key mediator in the activation of the hypothalamic-pituitary axis and in excess nitric oxide is the main factor accounting for abnormal pituitary response. Low adrenocorticotropin and vasopressin levels are likely the most deleterious consequences of the abnormal pituitary response, because they will contribute to shock and progression of inflammation with subsequent multiple organ failure and death.

Conclusions: Sepsis is associated with major changes in the hypothalamic-pituitary axis. The manipulation of the pituitary function during sepsis is a major challenge for the next decade.