Serum cortisol concentrations are approximately 20% lower with the newer assays compared with the older assays in some studies. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is a non-antibody, structural assay highly specific for cortisol. The Elecsys Cortisol generation II (Roche Diagnostics, City, IN) and Beckman Access Cortisol (Beckman Coulter, City, CA) immunoassays utilize monoclonal antibodies to identify cortisol. Conversely, it has been argued that very low cortisol values (ie, <3-6 µg/dL) may establish biochemical AI and thus obviate the need for dynamic CST. Furthermore, basal morning serum cortisol concentrations ranging from 11 to 19 µg/dL have been cited as a criterion to rule-out AI. īasal morning serum cortisol concentrations are also used to either increase the suspicion for, or rule-out the diagnosis of AI. Newer-generation assays with greater specificity for cortisol have been developed and have already replaced polyclonal antibody assays in many institutions. These assays had cross-reactivity with other serum steroids. Historically, immunoassays using polyclonal antibodies have been used to establish post-cosyntropin cortisol cutoff concentrations as high as 20 µg/dL. The CST cortisol cutoff threshold for the diagnosis of AI 30 or 60 minutes after ACTH administration has evolved over the years, but it has become entrenched at 18 µg/dL (500 nmol/L) despite improved specificity of newer cortisol assays. Accordingly, it has been abandoned in most clinical settings. Although insulin-induced hypoglycemia has previously been considered the gold standard test for decreased HPA axis function, it is very challenging to perform properly, labor intensive, and risky. Patients with primary AI always have an elevated plasma ACTH, so CST is typically not needed for confirmation of the diagnosis. ![]() CST assesses the maximum adrenocortical secretory response to a supraphysiologic dose of ACTH. Therefore, confirmation of the diagnosis of AI mandates precise biochemical testing, often requiring the assessment of adrenocorticotropic hormone (ACTH)-stimulated adrenal function to evaluate the integrity of hypothalamic-pituitary-adrenal (HPA) axis function.ĪCTH (synthetic ACTH cosyntropin synacthen) stimulation testing (CST) is the most commonly performed dynamic test to assess the adequacy of adrenal function in patients with suspected secondary adrenal insufficiency. Conversely, inappropriate assignment of AI to individuals has the potential for unnecessary glucocorticoid therapy. The accurate and swift diagnosis of adrenal insufficiency (AI) is imperative given the potential for life-threatening consequences if missed.
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