Updated Diagnostic Cortisol Values for Adrenal Insufficiency

Study Overview
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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.

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

Conditions
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Adrenal Insufficiency

Intervention / Treatment
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* Diagnostic Test: Cosyntropin stimulation test


Participation Criteria
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Eligibility Criteria
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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 eGFR < 60 mL/min/1.73m2 and/or diagnosis of nephrotic syndrome Pregnancy or nursing mothers Use of estrogen preparations Major depressive disorder, severe malnutrition, anorexia, 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, amino-glutethimide 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. 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 Regular use of opioids Regular use of suboxone Regular use of megestrol acetate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy volunteers<br>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<br>* 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.<br>|
| Active Comparator: Patients with known adrenal insufficiency<br>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<br>* 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.<br>|
| Active Comparator: Patients suspected to have adrenal insufficiency<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol threshold with cosyntropin stimulation test | To accurately re-define the cortisol threshold to diagnose adrenal insufficiency with cosyntropin stimulation test using the Alinity, monoclonal antibody, cortisol assay. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol threshold with basal, morning level | To determine a basal, morning, cortisol level above which adrenal insufficiency can be ruled out using the Alinity cortisol assay. | 1 day |