Adrenal Function in Critical Illness

NCT00156767 | Completed

• 2 other identifiers: 05001305-CH-0013
• Study Type: observational
• Target: 225
• Locations: 1 country
• Sites: 1

Brief Summary

An appropriate hypothalamic-pituitary-adrenal (HPA) axis response is required to survive critical illness. Primary adrenal insufficiency, relative adrenal insufficiency, tissue resistance to glucocorticoids, ACTH deficiency and immune-mediated inhibition of the HPA axis may impair the secretion or action of glucocorticoids in critically ill patients. Adrenal insufficiency is estimated to occur in up to 77% of critically ill patients, but currently, there is no consensus on the diagnostic criteria for adrenal insufficiency in this setting, and standard testing does not discriminate among the aforementioned factors. We will study the incidence and natural history of adrenal insufficiency in critically ill patients to further define adrenal insufficiency and provide data to develop diagnostic tests. Clinical features and outcomes will be correlated with laboratory measurements of hormones, cytokines and glucocorticoid action. Healthy volunteers will undergo cortrosyn tests with measurement of free cortisol levels to develop a normative range for this endpoint. \<TAB\> Previous glucocorticoid use, if prolonged and supraphysiologic, also inhibits the HPA and can result in adrenal insufficiency. Patients with short intermittent courses of glucocorticoid administration have not been studied well, and may also be at risk. To gain further information about this group, patients receiving pulse glucocorticoid doses as part of bone marrow transplant regimens at the Clinical Center will also be studied.

Conditions

Adrenal Insufficiency

Keywords

ACTH; Cortisol; Natural History

Outcome Measures

Primary Outcomes (1)

• Cortisol

  cortisol increase

  after ACTH

Study Arms (7)

Bone Marrow Transplant

Patients enrolled in an NCI protocols for bone marrow transplant for breast cancer using prednisone treatment.

Cirrhosis

Adults on NIDDK protocol 91-DK-0213 with evidence of chronic liver disease with class A or B cirrhosis secondary to viral hepatitis

Critical Care

Patients with a diagnosis of sepsis by the primary clinical provider in the Emergency room of ICU

Healthy Volunteer

Healthy adult volunteers

Known Adrenal Insufficiency

patients with known diagnosis of Adrenal Insufficiency

Nephrotic Syndrome

Adults enrolled in NIDDK protocols with diagnosis of nephrotic syndrome

Post Surgical Treatment for Cushings

Patients with transient adrenal insufficiency secondary to successful surgical treatment of cushing's syndrome

Eligibility Criteria

• Age: 15 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

NIH patients with Cushing's syndrome, adrenal insufficiency, hepatitis, nephrotic syndrome surrounding community healthy volunteers

You may qualify if:

• Diagnosis of sepsis by the primary clinical provider in the ICU.
• Diagnosis of the above is based on diagnostic criteria for sepsis as defined by the 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference as listed below:
• Infection, documented or suspected, and some of the following:
• General variables
• Fever (core temperature greater than 38.3 C)
• Hypothermia (core temperature greater than 36C)
• Heart Rate greater than 90 min or greater than 2 SD above the normal value for age
• Tachypnea
• Altered mental status
• Significant edema or positive fluid balance (greater than 20ml/kg over 24 hours)
• Hyperglycemia (plasma glucose greater than 120 mg/dl) in the absence of diabetes
• Inflammatory variables
• Leukocytosis (WBC count greater than 12,000 uL)
• Leukopenia (WBC count less than 4000 uL)
• Normal WBC count with greater than 10 percent immature forms

You may not qualify if:

• Pregnancy
• Age less than 15 years at the Clinical Center; age less than 18 years at Georgetown or Suburban Hospitals
• On glucocorticoids or megace within two weeks of admission unless using more than one of the following medications, patients taking inhaled corticosteriods (less than 1.5 mg/day budesonide, beclomethasone dipropionate and triamcinolone acetonide and less thab 0.75 mg/day for fluticasone propionate) or intranasal corticosteriods will not be excluded.
• Patients who have received chronic steroid suppressive medications, i.e. etomidate, ketoconazole (Patients receiving etomidate for intubation purposes as a one time dose will not be excluded)
• End stage renal or liver disease (creatinine clearance estimated as less than 20 cc/min by the cockcroft-gault equation: (140 - age) times lean body weight (kg)/ pCr (mg/dl) times 72, in patients with stable renal function; patients requiring dialysis; acute or fulminant hepatitis, alcoholic hepatitis, chronic severe hepatitis, severe obstructive hepatitis, severe coagulopathy, extrahepatic manifestations of ESLD, i.e. hypoxia, cardiomyopathy, acute renal failure)
• Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 l/six weeks in adults or 7 ml/kg/six weeks in children.
• BONE MARROW TRANSPLANT COMPONENT:
• Participation in a Clinical Center bone marrow transplant protocol for breast cancer (generally Allogeneic Breast Protocol 2: Phase 1 Trial of T cell Exchange with Th2/Tc2 Cells for Allogeneic Stem Cell Transplantation after Reduced Intensity Conditioning for Metastatic Breast Cancer), or for hematologic malignancy (generally either: T-cell depleted, reduced intensity allogeneic stem cell transplant from haploidentical related donors for hematologic malignancies: A sequential dose escalation study of donor Th2/Tc2 cells or Th2, Sirolimus in Allogeneic HSCT.
• Agreement from the oncologist PI that the patient may participate in this protocol.
• The presence of any contraindication to insulin tolerance testing-e.g.cardiovascular or cerebrovascular disease or any seizure history.
• Pregnancy
• Age less than 15 years
• End stage renal or liver disease as defined under the critical care section
• Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.
• HEALTHY VOLUNTEER COMPONENT:(Closed to recruitment)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Abraham SB, Abel BS, Sinaii N, Saverino E, Wade M, Nieman LK. Primary vs secondary adrenal insufficiency: ACTH-stimulated aldosterone diagnostic cut-off values by tandem mass spectrometry. Clin Endocrinol (Oxf). 2015 Sep;83(3):308-14. doi: 10.1111/cen.12726. Epub 2015 Mar 20.

  PMID: 25620457 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Adrenal Insufficiency

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Lynnette K Nieman, M.D.

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 12, 2005
• Study Start: November 12, 2004
• Last Updated: May 7, 2026

Record last verified: 2026-03-06

Locations

US (1)