What is the workup for possible adrenal insufficiency (Adrenal Insufficiency)?

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From the Guidelines

The workup for possible adrenal deficiency should begin with evaluating AM levels of ACTH and cortisol level, as well as a basic metabolic panel, renin, and aldosterone, as recommended by the most recent guidelines 1. When evaluating a patient for adrenal deficiency, it is essential to consider the relationship between ACTH and cortisol levels. Key steps in the workup include:

  • Evaluating AM levels of ACTH (if > 23 ULN) and cortisol level (if < 3 mg/dL) 1
  • Basic metabolic panel (Na, K, CO2, and glucose) to assess for electrolyte imbalances and other metabolic disturbances
  • Renin and aldosterone levels to evaluate the renin-angiotensin-aldosterone system
  • Consideration of a standard dose ACTH stimulation test for indeterminate results (AM cortisol < 3 mg/dL and < 15 mg/dL) 1
  • Evaluation for precipitating causes of crisis, such as infection
  • Adrenal CT for metastasis or hemorrhage, which are common causes of primary adrenal insufficiency 1 In cases where adrenal crisis is suspected, emergent therapy with hydrocortisone 100 mg IV should be initiated immediately, even before diagnostic confirmation, as this condition can be life-threatening 1. It is also crucial to educate patients on stress dosing and provide them with a medical alert bracelet for adrenal insufficiency to trigger stress-dose corticosteroids by EMS, as well as to consult with an endocrinologist prior to surgery or any procedure for stress-dose planning 1.

From the FDA Drug Label

INDICATIONS & USAGE Fludrocortisone acetate tablets, 0.1 mg are indicated as partial replacement therapy for primary and secondary adrenocortical insufficiency in Addison’s disease and for the treatment of salt-losing adrenogenital syndrome. The FDA drug label does not answer the question.

From the Research

Diagnostic Approach

The workup for possible adrenal deficiency involves a combination of clinical assessment and biochemical tests. The diagnosis of adrenal insufficiency is based on demonstrating low basal and/or stimulated serum cortisol levels 2. A short corticotropin test (250 μg) is considered the "gold standard" diagnostic tool to establish the diagnosis 3.

Laboratory Tests

Laboratory tests used to diagnose adrenal insufficiency include:

  • Basal hormone level measurements
  • Stimulation tests, such as the short corticotropin test
  • Measurement of morning plasma adrenocorticotropic hormone (ACTH) and cortisol levels 3
  • Validated assay of autoantibodies against 21-hydroxylase to diagnose the underlying cause 3

Clinical Features

Clinical features that may indicate adrenal insufficiency include:

  • Unintentional weight loss
  • Anorexia
  • Postural hypotension
  • Profound fatigue
  • Muscle and abdominal pain
  • Hyponatraemia
  • Skin hyperpigmentation (in primary adrenal insufficiency)
  • Salt cravings (in primary adrenal insufficiency) 4

Management

Management of adrenal insufficiency involves:

  • Glucocorticoid replacement therapy, typically with hydrocortisone or cortisone acetate 2, 5, 3
  • Mineralocorticoid replacement therapy in patients with primary adrenal insufficiency 2, 3
  • Patient education on managing adrenal insufficiency, including stress dosing and emergency administration of glucocorticoids 3, 4
  • Regular monitoring for features of under- and over-replacement 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Adrenal insufficiency - recognition and management.

Clinical medicine (London, England), 2017

Research

Adrenal insufficiency.

Lancet (London, England), 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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