The Importance of Adrenomedullin (AM) on ACTH-Cortisol-Glucose Axis

Condition(s) targeted: Systemic Inflammatory Response Syndrome; Hyperglycemia

Intervention: Blood AM, IL-6, ACTH, Cortisol, Glucose and Insulin (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: University of Sao Paulo

Official(s) and/or principal investigator(s):
Thelma Okay, PHD, Study Director, Affiliation: Childrens Institute / Molecular Biology

Hyperglycemia is frequent manifestations of the human metabolic response to systemic inflammatory response syndrome (SIRS),sepsis and septic shock, and are implicated in the clinical outcome.

Adrenomedullin is elevated in SIRS, sepsis and septic shock and has been demonstrated the inhibitory role on insulin and adrenocorticotropic hormone secretion.

Our hypothesis is that: AM elevation after SIRS could be the responsible to maintain hyperglycemia

Official title: The Importance of Adrenomedullin (AM) on Pituitary-Adrenal Axis and Glucose Kinetics in Pediatric Patients With Systemic Inflammatory Response Syndrome

Study design: Screening, Cross-Sectional, Defined Population, Prospective Study

Detailed description: Studies in cultured vascular endothelial cells and vascular smooth muscle cells demonstrate that cytokines strongly stimulate adrenomedullin production and release.

Adrenomedullin has been measured in a wide range of clinical researches. Of all conditions investigated, the greatest increment in plasma adrenomedullin has been observed in septic shock. It appears that AM is directly responsible for the hypotension characteristic of septic shock. Studies have shown that administration of AM and AMBP-1 before the onset of sepsis (i. e., pretreatment) prevents transition from the hyperdynamic phase to the hypodynamic phase in the progression of sepsis, attenuates tissue and organ damage, and reduces sepsis-induced mortality.

Two groups described the effects of AM on the pituitary. Taken together, these studies suggest that AM has a role in inhibiting ACTH release.

Mulder et al. first reported the stimulatory effects of adrenomedullin on insulin secretion from isolated rat islets. In direct contrast to this, Martínez et al. clearly demonstrated the inhibitory role of adrenomedullin on insulin secretion in vitro.

Minimum age: 2 Years. Maximum age: 16 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Children above 2 years, submitted to elective cardiopulmonary bypass (CPB, only

interatrial or ventricular communication) with no endocrine disease or infection.

Exclusion Criteria:

- Children with endocrine disease, undernutrition, with some medication that might

interfere in the study (corticosteroids.

Childrens Institute, Sao Paulo, SP 05403000, Brazil

Starting date: January 2006
Ending date: October 2006
Last updated: April 11, 2007