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.

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.

Further Study Details: 

Expected Total Enrollment:  60

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.

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.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:

Diagnosis of sepsis by the primary clinical provider in the ICU.

Healthy male or female 15 years of age or older

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 38.8 C)

-Hypothermia (core temperature less 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% immature forms

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

-Plasma procalcitonin greater than 2SD 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%

Cardiac Index greater than 3.5L min(-1) M(-23).

EXCLUSION CRITERIA:

Pregnancy

Any acute or chronic illness at time of evaluation

Use of oral or topical glucocorticoids in the last 12 months

Use of any antifungal medication in the last 12 months

Pediatric patients (age less than 15 years)

On glycocorticoids or megace within two weeks of admission.

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) x lean body weight (kg)/ pCr (mg/dl) x 72, in patients with stable renal function; patients requiring dialysis; acute or fulminant hepatitis, alcohol hepatitis, chronic severe hepatitis, severe obstructive hepatitis, severe coagulopathy, extrahepatic manifestations of ESLD, i.e. hypoxia, cardiomyopathy, acute renal failure)

Immunosuppressive therapy after organ transplant

Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/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.

EXCLUSION CRITERIA:

The presence of any contraindication to insulin tolerance testing-e.g.cardiovascular or cerebrovascular disease or any seizure history.

-Pregnancy

-Pediatric patients (age less than 18 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

Adults aged at least 18 years will be recruited.

EXCLUSION CRITERIA:

Any acute or chronic illness at time of evaluation

Use of oral or topical glucocorticoids in the last 12 months

Use of any antifungal medication in the last 12 months

Pregnancy

Please refer to this study by ClinicalTrials.gov identifier  NCT00156767

Maryland
      National Institute of Child Health and Human Development (NICHD), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  050013; 05-CH-0013
Last Updated:  September 9, 2005
Record first received:  September 9, 2005
ClinicalTrials.gov Identifier:  NCT00156767
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-09-13