Updated Diagnostic Cortisol Values for Adrenal Insufficiency

February 18, 2026 updated by: Montefiore Medical Center

Re-assessment of Diagnostic Cortisol Values for Adrenal Insufficiency Using a Highly Specific Cortisol Assay

The purpose of this study is to determine the cortisol levels that most accurately diagnose a patient with adrenal insufficiency, a condition in which cortisol levels are too low for daily living.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this study, a cosyntropin (ACTH) stimulation test will be conducted by administering intramuscular cosyntropin into a subject's arm and measuring cortisol levels before and after injection. Cosyntropin tests are routine medical tests that are done in doctors' offices to diagnose adrenal insufficiency. Cosyntropin is a synthetic version of a hormone, called ACTH, that is secreted by our bodies to help produce cortisol. Participation in this research will last about two hours.

Aim # 1:

The primary aim is to accurately re-define the cortisol threshold to diagnose adrenal insufficiency with cosyntropin stimulation test using the Alinity, monoclonal antibody, cortisol assay.

Aim # 2:

The secondary aims are to determine a basal, morning, cortisol level above which adrenal insufficiency can be ruled out using the Alinity cortisol assay and to compare diagnostic cortisol thresholds within the cosyntropin stimulation test between the Abbott Alinity assay and the Roche 2 assay.

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria for healthy volunteers:

- Male and female outpatients 18 years or older without prior diagnosis of primary or central adrenal insufficiency

Inclusion Criteria for patients with known adrenal insufficiency:

- Males and females 18 years or older with established diagnosis of primary or central adrenal insufficiency as previously documented in the electronic medical record by a failed CST (peak cortisol level < 18 μg/dL) or morning serum cortisol < 3 mcg/dL with an appropriate clinical circumstance (e.g., Sheehan's syndrome, pituitary surgery and/or irradiation, bilateral adrenalectomy, etc.) that strongly supports a true diagnosis of primary or central adrenal insufficiency, and current use of physiologic, replacement dose glucocorticoids. Inpatients with non-critical illness and outpatients are eligible

Inclusion Criteria for patients with suspected adrenal insufficiency:

- Males and females 18 years or older with suspected diagnosis of primary or central adrenal insufficiency by any cause based on clinical evaluation by a study team member. Inpatients with non-critical illness and outpatients are eligible

Exclusion Criteria for all groups:

  • Moderate to severe liver impairment or abnormal albumin or cortisol binding globulin concentrations
  • Renal impairment with estimated Glomerular Filtration Rate (eGFR) < 60 mL/min/1.73m2 and/or diagnosis of nephrotic syndrome
  • Pregnancy or nursing mothers
  • Use of estrogen preparations
  • Uncontrolled major depressive disorder or psychiatric diseases, severe malnutrition, eating disorders, chronic fatigue syndrome (disorders that alter hypothalamic-pituitary-adrenal (HPA) axis function)
  • Use of any medications that induce hepatic cytochrome P-450 enzymes, e.g., barbiturates, phenytoin, rifampin, aminoglutethimide and mitotane
  • Active medical treatment of Cushing's syndrome (status-post surgical treatment is acceptable)
  • Uncontrolled hypo- or hyperthyroidism
  • Use of biotin within the past 72 hours
  • Regular alcohol and/or cannabis use
  • History of bilateral adrenalectomy
  • Treatment for validated primary adrenal insufficiency for greater than 6 months
  • Be assessed by the investigators as unsuitable for participation in this study for any reason

Additional Exclusion Criteria for healthy volunteers only:

  • Regular use of any oral glucocorticoid (e.g. hydrocortisone, prednisone, dexamethasone) within 6 weeks of the screening visit
  • Use of oral or nasal steroid (glucocorticoid) inhalers in the past 2 weeks
  • Regular use of any steroid creams, gels, ointments, or lotions
  • Use of steroid (glucocorticoid) injections in the past 6 months (healthy volunteers)
  • Regular use of opioids
  • Regular use of suboxone
  • Regular use of megestrol acetate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Healthy volunteers
Healthy volunteers are those 18 years or older without prior diagnosis of adrenal insufficiency. Study participation by healthy volunteers helps us understand what cortisol levels should be in a healthy population. This information also helps us figure out what levels might be in people with adrenal insufficiency.
Diagnostic test: Cosyntropin stimulation test
In this test, Cosyntropin is administered as an intramuscular injection into the arm. Cortisol levels are measured before and after injection. Cosyntropin tests are routine medical tests that are done in doctors' offices to diagnose adrenal insufficiency. Cosyntropin is a synthetic version of a hormone, called ACTH, that is secreted by our bodies to help produce cortisol.
Active Comparator: Patients with known adrenal insufficiency
This group consists of patients 18 years or older with an established diagnosis of adrenal insufficiency. Study participation by patients with adrenal insufficiency helps us understand what cortisol levels should be, in the new assays, among those with adrenal insufficiency.
Diagnostic test: Cosyntropin stimulation test
In this test, Cosyntropin is administered as an intramuscular injection into the arm. Cortisol levels are measured before and after injection. Cosyntropin tests are routine medical tests that are done in doctors' offices to diagnose adrenal insufficiency. Cosyntropin is a synthetic version of a hormone, called ACTH, that is secreted by our bodies to help produce cortisol.
Active Comparator: Patients suspected to have adrenal insufficiency
This groups consists of patients 18 years or older who are suspected to have adrenal insufficiency. Study participation by this group will help us understand if the cortisol values we get from the new assay accurately diagnose adrenal insufficiency.
Diagnostic test: Cosyntropin stimulation test
In this test, Cosyntropin is administered as an intramuscular injection into the arm. Cortisol levels are measured before and after injection. Cosyntropin tests are routine medical tests that are done in doctors' offices to diagnose adrenal insufficiency. Cosyntropin is a synthetic version of a hormone, called ACTH, that is secreted by our bodies to help produce cortisol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortisol threshold with cosyntropin stimulation test
Time Frame: 0 minutes (pre-cosyntropin administration) and 30 and 60 minutes post-cosyntropin administration; up to 2 hours participation time
To accurately re-define the cortisol threshold to diagnose adrenal insufficiency (AI) with cosyntropin stimulation test (CST) using the Alinity, monoclonal antibody, cortisol assay. The cortisol threshold for the diagnosis of AI using the Alinity assay is 18 ug/dL. Results from the CST assay will be summarized by study arm/group to determine a new cut-point for patients with suspected primary or central AI.
0 minutes (pre-cosyntropin administration) and 30 and 60 minutes post-cosyntropin administration; up to 2 hours participation time

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cortisol threshold with basal, morning level
Time Frame: 0 minutes (pre-cosyntropin administration) and 30 and 60 minutes post-cosyntropin administration; up to 2 hours participation time
To determine a basal, morning, cortisol level above which adrenal insufficiency can be ruled out using the Alinity cortisol assay. Results will be summarized by study arm,
0 minutes (pre-cosyntropin administration) and 30 and 60 minutes post-cosyntropin administration; up to 2 hours participation time

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Collaborators

Medical College of Wisconsin

Investigators

  • Principal Investigator: Smita B Abraham, MD, Albert Einstein - Montefiore Medical Center, Bronx, New York

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2022

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

November 24, 2021

First Submitted That Met QC Criteria

November 24, 2021

First Posted (Actual)

December 8, 2021

Study Record Updates

Last Update Posted (Actual)

February 19, 2026

Last Update Submitted That Met QC Criteria

February 18, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-13420

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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