Adrenal Failure: An Evidence-Based Diagnostic Approach

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,...

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Main Authors: Salomi Shaikh, Lakshmi Nagendra, Shehla Shaikh, Joseph M. Pappachan
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/13/10/1812
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author Salomi Shaikh
Lakshmi Nagendra
Shehla Shaikh
Joseph M. Pappachan
author_facet Salomi Shaikh
Lakshmi Nagendra
Shehla Shaikh
Joseph M. Pappachan
author_sort Salomi Shaikh
collection DOAJ
description 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.
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spelling doaj.art-6b36811483be4b39aedba93402850d832023-11-18T01:05:41ZengMDPI AGDiagnostics2075-44182023-05-011310181210.3390/diagnostics13101812Adrenal Failure: An Evidence-Based Diagnostic ApproachSalomi Shaikh0Lakshmi Nagendra1Shehla Shaikh2Joseph M. Pappachan3KGN Diabetes and Endocrine Centre, Mumbai 400001, IndiaDepartment of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research Center, Mysore 570015, IndiaDepartment of Endocrinology, Saifee Hospital, Mumbai 400004, IndiaDepartment of Endocrinology & Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston PR2 9HT, UKThe 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.https://www.mdpi.com/2075-4418/13/10/1812adrenal failurecortisoladrenocorticotrophin (ACTH)primary adrenal insufficiency (PAI)secondary adrenal insufficiency (SAI)
spellingShingle Salomi Shaikh
Lakshmi Nagendra
Shehla Shaikh
Joseph M. Pappachan
Adrenal Failure: An Evidence-Based Diagnostic Approach
Diagnostics
adrenal failure
cortisol
adrenocorticotrophin (ACTH)
primary adrenal insufficiency (PAI)
secondary adrenal insufficiency (SAI)
title Adrenal Failure: An Evidence-Based Diagnostic Approach
title_full Adrenal Failure: An Evidence-Based Diagnostic Approach
title_fullStr Adrenal Failure: An Evidence-Based Diagnostic Approach
title_full_unstemmed Adrenal Failure: An Evidence-Based Diagnostic Approach
title_short Adrenal Failure: An Evidence-Based Diagnostic Approach
title_sort adrenal failure an evidence based diagnostic approach
topic adrenal failure
cortisol
adrenocorticotrophin (ACTH)
primary adrenal insufficiency (PAI)
secondary adrenal insufficiency (SAI)
url https://www.mdpi.com/2075-4418/13/10/1812
work_keys_str_mv AT salomishaikh adrenalfailureanevidencebaseddiagnosticapproach
AT lakshminagendra adrenalfailureanevidencebaseddiagnosticapproach
AT shehlashaikh adrenalfailureanevidencebaseddiagnosticapproach
AT josephmpappachan adrenalfailureanevidencebaseddiagnosticapproach