Adrenal Failure: An Evidence-Based Diagnostic Approach

Abstract

The diagnosis of adrenal insufficiency (AI) requires a high index of suspicion, detailed clinical assessment including detailed drug history, and appropriate laboratory evaluation. The clinical characteristics of adrenal insufficiency vary according to the cause, and the presentation may be myriad, e.g. insidious onset to a catastrophic adrenal crisis presenting with circulatory shock and coma. Secondary adrenal insufficiency (SAI) often presents with only glucocorticoid deficiency because aldosterone production, which is controlled by the renin angiotensin system, is usually intact, and rarely presents with an adrenal crisis. Measurements of the basal serum cortisol at 8 am (<140 nmol/L or 5 mcg/dL) coupled with adrenocorticotrophin (ACTH) remain the initial tests of choice. The cosyntropin stimulation (short synacthen) test is used for the confirmation of the diagnosis. Newer highly specific cortisol assays have reduced the cut-off points for cortisol in the diagnosis of AI. The salivary cortisol test is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels such as pregnancy. Children and infants require lower doses of cosyntropin for testing. 21-hydoxylase antibodies are routinely evaluated to rule out autoimmunity, the absence of which would require secondary causes of adrenal insufficiency to be ruled out. Testing the hypothalamic–pituitary–adrenal (HPA) axis, imaging, and ruling out systemic causes are necessary for the diagnosis of AI. Cancer treatment with immune checkpoint inhibitors (ICI) is an emerging cause of both primary AI and SAI and requires close follow up. Several antibodies are being implicated, but more clarity is required. We update the diagnostic evaluation of AI in this evidence-based review.

Serum ACTH and Cortisol Level is Associated with the Acute Gastrointestinal Injury Grade in ICU Patients

“…It is recommended to use a stimulation test to evaluate HPA function to diagnose CIRCI. However, studies have shown that the relationship between test results and patient outcomes is unclear, 22 while the risk of GI bleeding increases even after low dose of dexamethasone admission in the test. So the stimulation test should only do when CIRCI was highly suspected.…”

Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis)

“…Negative results of the test with undetectable plasma cortisol suggested a secondary adrenal insufficiency in a 45-year-old male with bilateral foci of auricular ossifications (and negative endocrine autoimmunity) [ 28 ]. ACTH stimulation test remains a practical approach of the adrenal insufficiency diagnosis (including partial or latent forms) amid the presence of the rigid ears according to the general endocrine practice [ 59 , 60 , 61 , 62 , 63 ]. Another important issue included the evaluation of the metabolic features such as diabetes mellitus (four subjects within the endocrine cohort [ 1 , 21 , 34 , 38 ], but, also, two other patients in the non-endocrine cohort [ 46 , 50 ], had the condition, as well as one case of hypercholesterolemia [ 41 ]).…”

“…Negative results of the test with undetectable plasma cortisol suggested a secondary adrenal insufficiency in a 45-year-old male with bilateral foci of auricular ossifications (and negative endocrine autoimmunity) [ 28 ]. ACTH stimulation test remains a practical approach of the adrenal insufficiency diagnosis (including partial or latent forms) amid the presence of the rigid ears according to the general endocrine practice [ 59 , 60 , 61 , 62 , 63 ].…”