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