Updated Diagnostic Cortisol Values for Adrenal Insufficiency

NCT ID: NCT05149638

Last Updated: 2026-01-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-03

Study Completion Date

2027-12-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Adrenal Insufficiency

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

A prospective, cross-sectional study design consisting of one study visit during which the study participant will undergo cosyntropin stimulation test. The three groups in the study are healthy volunteers (HV; n = 30), patients with known primary or central adrenal insufficiency (n = 30), and patients suspected to have primary or central adrenal insufficiency (n = 30).
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Cosyntropin stimulation test

Intervention Type DIAGNOSTIC_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.

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.

Group Type ACTIVE_COMPARATOR

Cosyntropin stimulation test

Intervention Type DIAGNOSTIC_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.

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.

Group Type ACTIVE_COMPARATOR

Cosyntropin stimulation test

Intervention Type DIAGNOSTIC_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.

Interventions

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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.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

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


\- 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

* Moderate to severe liver impairment or abnormal albumin or cortisol binding globulin concentrations
* Renal impairment with 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 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
* Be assessed by the investigators as unsuitable for participation in this study for any reason


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Medical College of Wisconsin

OTHER

Sponsor Role collaborator

Montefiore Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Smita B Abraham, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein - Montefiore Medical Center, Bronx, New York

Locations

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Montefiore Medical Center

The Bronx, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Smita B Abraham, MD

Role: CONTACT

718-839-7322

Noah Bloomgarden, MD

Role: CONTACT

Facility Contacts

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Smita Abraham, MD

Role: primary

Noah Bloomgarden, MD

Role: backup

References

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Hahner S, Spinnler C, Fassnacht M, Burger-Stritt S, Lang K, Milovanovic D, Beuschlein F, Willenberg HS, Quinkler M, Allolio B. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015 Feb;100(2):407-16. doi: 10.1210/jc.2014-3191. Epub 2014 Nov 24.

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Giordano R, Marzotti S, Balbo M, Romagnoli S, Marinazzo E, Berardelli R, Migliaretti G, Benso A, Falorni A, Ghigo E, Arvat E. Metabolic and cardiovascular profile in patients with Addison's disease under conventional glucocorticoid replacement. J Endocrinol Invest. 2009 Dec;32(11):917-23. doi: 10.1007/BF03345773. Epub 2009 Jul 20.

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Oelkers W. Adrenal insufficiency. N Engl J Med. 1996 Oct 17;335(16):1206-12. doi: 10.1056/NEJM199610173351607. No abstract available.

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PMID: 8815944 (View on PubMed)

Dorin RI, Qiao Z, Qualls CR, Urban FK 3rd. Estimation of maximal cortisol secretion rate in healthy humans. J Clin Endocrinol Metab. 2012 Apr;97(4):1285-93. doi: 10.1210/jc.2011-2227. Epub 2012 Feb 15.

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PMID: 22337905 (View on PubMed)

Reimondo G, Bovio S, Allasino B, Terzolo M, Angeli A. Secondary hypoadrenalism. Pituitary. 2008;11(2):147-54. doi: 10.1007/s11102-008-0108-4.

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PMID: 18418713 (View on PubMed)

Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, Torpy DJ. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 Feb;101(2):364-89. doi: 10.1210/jc.2015-1710. Epub 2016 Jan 13.

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PMID: 26760044 (View on PubMed)

Raverot V, Richet C, Morel Y, Raverot G, Borson-Chazot F. Establishment of revised diagnostic cut-offs for adrenal laboratory investigation using the new Roche Diagnostics Elecsys(R) Cortisol II assay. Ann Endocrinol (Paris). 2016 Oct;77(5):620-622. doi: 10.1016/j.ando.2016.05.002. Epub 2016 Jul 19. No abstract available.

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Kline GA, Buse J, Krause RD. Clinical implications for biochemical diagnostic thresholds of adrenal sufficiency using a highly specific cortisol immunoassay. Clin Biochem. 2017 Jun;50(9):475-480. doi: 10.1016/j.clinbiochem.2017.02.008. Epub 2017 Feb 10.

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PMID: 28192125 (View on PubMed)

Javorsky BR, Raff H, Carroll TB, Algeciras-Schimnich A, Singh RJ, Colon-Franco JM, Findling JW. New Cutoffs for the Biochemical Diagnosis of Adrenal Insufficiency after ACTH Stimulation using Specific Cortisol Assays. J Endocr Soc. 2021 Feb 18;5(4):bvab022. doi: 10.1210/jendso/bvab022. eCollection 2021 Apr 1.

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Reference Type BACKGROUND
PMID: 2868172 (View on PubMed)

Other Identifiers

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2021-13420

Identifier Type: -

Identifier Source: org_study_id

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