• EXCLUSION CRITERIA - ALL ARMS OF STUDY

Women of reproductive age will also undergo a pregnancy test (urine hCG) prior to starting the testing procedure. If the woman is determined to be pregnant, she will not be able to participate in this study.

INCLUSION CRITERIA - CRITICAL CARE COMPONENT:

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
• Plasma C-reactive protein greater than 2 SD above the normal value
• Plasma procalcitonin greater than 2 SD above the normal value

Hemodynamic variables

• Arterial hypotension (SBP less than 90mm Hg, MAP less than 70, or an SBP decrease greater than 40 mm Hg in adults or less than 2 SD below normal for age)
• SvO2 greater than 70 percent
• Cardiac Index greater than 3.5L min(-1) M(-23)

EXCLUSION CRITERIA - CRITICAL CARE COMPONENT:

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.

INCLUSION CRITERIA - 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.

EXCLUSION CRITERIA - BONE MARROW TRANSPLANT COMPONENT:

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.

INCLUSION CRITERIA - HEALTHY VOLUNTEER COMPONENT:

Adults aged at least 18 years will be recruited.

EXCLUSION CRITERIA - HEALTHY VOLUNTEER COMPONENT:

Severe hepatic, renal, cardiac, psychiatric or neurological illnesses

More than two weeks of oral antifungal or glucocorticoid medications or near daily use of topical glucocorticoids with broken skin. Frequent use of topical antifungal agents will be considered on a case-by-case basis.

Pregnancy

INCLUSION CRITERIA - KNOWN ADRENAL INSUFICIENTY COMPONENT:

Documented longstanding primary or secondary adrenal insufficiency

EXCLUSION CRITERIA - KNOWN ADRENAL INSUFFICNCY COMPONENT:

Pregnancy

INCLUSION CRITERIA - TRANSIENT ADRENAL INSUFICIENTY COMPONENT:

Recent uncomplicated successful transsphemoidal surgery for Cushing's disease with serum cortisol level less than 5 micro g/dl

EXCLUSION CRITERIA - TRANSIENT ADRENAL INSUFFICNCY COMPONENT:

Supra physiologic dosing of glucocorticoids as a treatment for another underlying medical disorder or surgical complication

Pregnancy