Adrenal InsufficiencyNCT00156767
Adrenal Function in Critical Illness
An observational study of Adrenal Insufficiency, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 65 years
- Conditions the study is for
- Adrenal Insufficiency
- How many people
- 225 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2004to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: NIH patients with Cushing's syndrome, adrenal insufficiency, hepatitis, nephrotic syndrome surrounding community healthy volunteers
Who may be able to join
- 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)
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- 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)
- 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.
- Adults aged at least 18 years will be recruited.
- Documented longstanding primary or secondary adrenal insufficiency
- Recent uncomplicated successful transsphemoidal surgery for Cushing s disease with serum cortisol level less than 5 micro g/dl
- TRANSIENT ADRENAL INSUFFICIENCY COMPONENT:
- Participation in an active NIDDK protocol entitled: Evaluation of patients with liver disease (91-DK-0214), with evidence of chronic liver disease
- Agreement from the hepatologist PI that the patient may participate in this protocol.
- Child-Pugh class A or B cirrhosis secondary to viral hepatitis
- Absence of other significant medical illnesses that might interfere with prolonged follow-up evaluation
- Normal renal function (creatinine clearance estimated as > 60 ml/min by the Modified Diet in Renal Disease (MDRD) equation and reported through our Clinical Research Information System (CRIS)).
- Participation in one of three active NIDDK protocols entitled: Rituximab plus cyclosporine in idiopathic membranous nephropathy (09-DK-0223), the Nephrotic Syndrome Study Network (Neptune) (11-DK-0023), or Pathogenesis of Glomerulosclerosis Study (94-DK-0127) with previously documented proteinuria >3.5g/day for 2 months or more or protein/creatinine ratio of 2.0 g/g on at least 2 occasions
- Agreement from the nephrologist PI that the patient may participate in this protocol. Estimated GFR greater than or equal to 30 ml/min based on the MDRD equation and reported through CRIS.
- Normal liver function as defined by normal liver function tests and no known history of liver disease.
Who cannot join
- 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.
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- 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.
- HEALTHY VOLUNTEER COMPONENT:(Closed to recruitment)
- 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
- KNOWN ADRENAL INSUFFICIENCY COMPONENT:
- Pregnancy
- TRANSIENT ADRENAL INSUFFICIENCY COMPONENT:
- Supra physiologic dosing of glucocorticoids as a treatment for another underlying medical disorder or surgical complication
- Pregnancy
- CIRRHOSIS AND NEPHROTIC SYNDROME COMPONENT:
- Adults aged at least 18 years will be recruited.
- CIRRHOSIS
- History of the use of glucocorticoid therapy or medications that are known to interfere with HPA axis function within the past 6 months
- Current symptoms of adrenal insufficiency (nausea, vomiting, weight loss, lightheadedness, unusual fatigue, salt craving, etc.).
- Evidence of moderate-severe medical illness attributable to obstructive sleep apnea, heart or pulmonary failure, or active malignancy will be excluded.
- Pregnancy
- Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.
- NEPHROTIC SYNDROME:
- History of the use of glucocorticoid therapy or medications that are known to interfere with HPA axis function within the past 6 months
- Current symptoms of adrenal insufficiency (nausea, vomiting, weight loss, lightheadedness, unusual fatigue, salt craving, etc.).
- Evidence of moderate-severe medical illness attributable to obstructive sleep apnea, heart or pulmonary failure, or active malignancy will be excluded.
- Pregnancy
- Known or anticipated blood withdrawal within 6 weeks that exceeds the NIH guidelines of 450 ml/six weeks in adults.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read the detailed description
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 percent 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. Patients with known adrenal insufficiency will also be studied to help determine the clinical utility of diagnostic tests among these different groups. Previous glucocorticoid use, if prolonged and supraphysiologic, also inhibits the HPA axis 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
- Medical subject headings
- Adrenal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortisol
cortisol increase
Measured: after ACTH
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2005 (estimated)
- Study start12 Nov 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adrenal InsufficiencyStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 225 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lynnette K Nieman, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00156767
- Sponsor's protocol ID
- 050013
- Other IDs
- 05-CH-0013
- Status last verified
- 15 Oct 2026
- First submitted
- 9 Sep 2005
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 25620457
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adrenal Function in Critical Illness
- ClinicalTrials.gov ID
- NCT00156767
- Acronym / sponsor ID
- 050013
- Conditions
- Adrenal Insufficiency
- Keywords
- ACTH, Cortisol, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 225 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 12 Nov 2004 (actual)
- First posted
- 12 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 percent 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. Patients with known adrenal insufficiency will also be studied to help determine the clinical utility of diagnostic tests among these different groups. Previous glucocorticoid use, if prolonged and supraphysiologic, also inhibits the HPA axis 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 15 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- NIH patients with Cushing's syndrome, adrenal insufficiency, hepatitis, nephrotic syndrome surrounding community healthy volunteers
Key inclusion criteria (35 listed)
- 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:
- General variables
- Fever (core temperature greater than 38.3 C)
- Hypothermia (core temperature greater than 36C)
Key exclusion criteria (35 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cortisol
Time frame: after ACTH
cortisol increase
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Derived from this study: PubMed 25620457Abraham 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynnette K Nieman, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Adrenal Insufficiency, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortisol (time frame: after ACTH). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00156767, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026; AzTrials last refreshed its copy on 28 Oct 2026.