Updated Diagnostic Cortisol Values for Adrenal Insufficiency

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