Clinical trial NCT00459511: The Importance of Adrenomedullin (AM) on ACTH-Cortisol-Glucose Axis
Official title: The Importance of Adrenomedullin (AM) on Pituitary-Adrenal Axis and Glucose Kinetics in Pediatric Patients With Systemic Inflammatory Response Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Systemic Inflammatory Response Syndrome
Hyperglycemia
Keywords: Adrenomedullin
Glucose
Insulin
Systemic Inflammatory response Syndrome
Pediatric
Cortisol
ACTH
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
First posted: 2007-04-12
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: DEFINED_POPULATION
Time perspective: OTHER

Brief summary: 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

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.

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Childrens Institute
state: SP
Study officials:
affiliation: Childrens Institute / Molecular Biology
name: Thelma Okay, PHD
role: STUDY_DIRECTOR
References:
citation: Martinez A, Weaver C, Lopez J, Bhathena SJ, Elsasser TH, Miller MJ, Moody TW, Unsworth EJ, Cuttitta F. Regulation of insulin secretion and blood glucose metabolism by adrenomedullin. Endocrinology. 1996 Jun;137(6):2626-32. doi: 10.1210/endo.137.6.8641217.
citation: Zhou M, Simms HH, Wang P. Adrenomedullin and adrenomedullin binding protein-1 attenuate vascular endothelial cell apoptosis in sepsis. Ann Surg. 2004 Aug;240(2):321-30. doi: 10.1097/01.sla.0000133253.45591.5b.
citation: Koo DJ, Zhou M, Chaudry IH, Wang P. The role of adrenomedullin in producing differential hemodynamic responses during sepsis. J Surg Res. 2001 Feb;95(2):207-18. doi: 10.1006/jsre.2000.6013.
citation: Yoshikawa D, Kawahara F, Okano N, Hiraoka H, Kadoi Y, Fujita N, Morita T, Goto F. Increased plasma concentrations of the mature form of adrenomedullin during cardiac surgery and hepatosplanchnic hypoperfusion. Anesth Analg. 2003 Sep;97(3):663-670. doi: 10.1213/01.ANE.0000072543.78106.AA.
citation: Takeuchi M, Morita K, Iwasaki T, Toda Y, Oe K, Taga N, Hirakawa M. Significance of adrenomedullin under cardiopulmonary bypass in children during surgery for congenital heart disease. Acta Med Okayama. 2001 Aug;55(4):245-52. doi: 10.18926/AMO/31995.
citation: Rossi GP, Conconi MT, Malendowicz LK, Nussdorfer GG. Role of the endogenous adrenomedullin system in regulating the secretion and growth of rat adrenal cortex. Hypertens Res. 2003 Feb;26 Suppl:S85-92. doi: 10.1291/hypres.26.s85.
citation: Kapas S, Martinez A, Cuttitta F, Hinson JP. Local production and action of adrenomedullin in the rat adrenal zona glomerulosa. J Endocrinol. 1998 Mar;156(3):477-84. doi: 10.1677/joe.0.1560477.