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

Purpose

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

Condition	Intervention	Phase
Systemic Inflammatory Response Syndrome Hyperglycemia	Procedure: Blood AM, IL-6, ACTH, Cortisol, Glucose and Insulin	Phase 2

Study Type:	Observational
Study Design:	Observational Model: Defined Population Primary Purpose: Screening Time Perspective: Cross-Sectional Time Perspective: Prospective
Official Title:	The Importance of Adrenomedullin (AM) on Pituitary-Adrenal Axis and Glucose Kinetics in Pediatric Patients With Systemic Inflammatory Response Syndrome

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Medicines Hyperglycemia Shock

Drug Information available for: Hydrocortisone acetate Hydrocortisone Hydrocortisone sodium succinate Hydrocortisone cypionate Insulin human Hydrocortisone butyrate Dextrose Hydrocortisone valerate Hydrocortisone probutate

U.S. FDA Resources

Further study details as provided by University of Sao Paulo:

Estimated Enrollment:	20
Study Start Date:	January 2006
Study Completion Date:	October 2006

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

Ages Eligible for Study:	2 Years to 16 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459511

Locations

Brazil
Childrens Institute
Sao Paulo, SP, Brazil, 05403000

Sponsors and Collaborators

University of Sao Paulo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.

Investigators

Study Director:

Thelma Okay, PHD

Childrens Institute / Molecular Biology

More Information

Publications:

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.

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.

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. Review.

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):663-70.

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.

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.

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.

ClinicalTrials.gov Identifier:	NCT00459511 History of Changes
Other Study ID Numbers:	FMUSP/ cappesq 675/05
Study First Received:	April 11, 2007
Last Updated:	April 11, 2007
Health Authority:	Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo:

Adrenomedullin
Glucose
Insulin
Systemic Inflammatory response Syndrome

Pediatric
Cortisol
ACTH

Additional relevant MeSH terms:

Hyperglycemia
Systemic Inflammatory Response Syndrome
Glucose Metabolism Disorders
Metabolic Diseases
Inflammation
Pathologic Processes
Shock
Adrenocorticotropic Hormone
Insulin
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Adrenomedullin

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hypoglycemic Agents
Anti-Inflammatory Agents
Therapeutic Uses
Dermatologic Agents
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Cardiotonic Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on June 18, 2013