What laboratory tests are used to diagnose adrenal insufficiency (Addison's disease)?

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From the Guidelines

To check for adrenal insufficiency, the most important laboratory tests include morning serum cortisol, ACTH stimulation test, plasma ACTH level, and comprehensive metabolic panel, as recommended by the most recent guidelines 1. When evaluating a patient for adrenal insufficiency, it is essential to consider the following key laboratory tests:

  • Morning serum cortisol level: A level below 3 mg/dL suggests adrenal insufficiency, while a level above 15 mg/dL typically rules it out 1.
  • ACTH stimulation test: This is the gold standard diagnostic test, where synthetic ACTH (cosyntropin) is administered intravenously and cortisol levels are measured at baseline, 30, and 60 minutes; a peak cortisol response below 18 mcg/dL indicates adrenal insufficiency 1.
  • Plasma ACTH level: This helps differentiate between primary (elevated ACTH) and secondary (low or normal ACTH) adrenal insufficiency 1.
  • Comprehensive metabolic panel: This includes electrolytes (looking for hyponatremia, hyperkalemia), glucose (hypoglycemia), BUN and creatinine, and renin and aldosterone levels 1. Additional tests, such as 21-hydroxylase antibodies, may be useful in suspected autoimmune adrenal insufficiency 1. It is crucial to perform these tests before initiating corticosteroid therapy, as exogenous steroids can interfere with test results 1.

From the Research

Labs to Check for Adrenal Insufficiency

To diagnose adrenal insufficiency, several laboratory tests can be utilized, including:

  • Serum cortisol measurement: This test measures the level of cortisol in the blood, which can help diagnose adrenal insufficiency 2, 3, 4, 5.
  • Adrenocorticotropic hormone (ACTH) stimulation test: This test measures the response of the adrenal glands to ACTH, which can help diagnose primary and secondary adrenal insufficiency 5, 6.
  • Cosyntropin stimulation test: This test is similar to the ACTH stimulation test and can help diagnose adrenal insufficiency 4.

Diagnostic Criteria

The diagnostic criteria for adrenal insufficiency vary depending on the test used:

  • Serum cortisol measurement: A morning serum cortisol level of <275 nmol/L or an afternoon level of <250 nmol/L can indicate adrenal insufficiency 2.
  • ACTH stimulation test: A peak serum cortisol level of <550 nmol/L (high-dose test) or <500 nmol/L (low-dose test) can indicate adrenal insufficiency 5.
  • Cosyntropin stimulation test: A cortisol level of <14.6 μg/dL at 60 minutes after stimulation can indicate adrenal insufficiency 4.

Test Sensitivity and Specificity

The sensitivity and specificity of these tests vary:

  • Serum cortisol measurement: A morning serum cortisol level of <275 nmol/L has a sensitivity of 96.2% and a specificity of 95.8% 2.
  • ACTH stimulation test: The high-dose test has a sensitivity of 92% and a specificity of 96% 5.
  • Cosyntropin stimulation test: A cortisol level of <14.6 μg/dL at 60 minutes after stimulation has a sensitivity of 92% and a specificity of 96% 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

SERUM MORNING CORTISOL AS A SCREENING TEST FOR ADRENAL INSUFFICIENCY.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2020

Research

New Diagnostic Cutoffs for Adrenal Insufficiency After Cosyntropin Stimulation Using Abbott Architect Cortisol Immunoassay.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2022

Research

DIAGNOSTIC ACCURACY OF BASAL CORTISOL LEVEL TO PREDICT ADRENAL INSUFFICIENCY IN COSYNTROPIN TESTING: RESULTS FROM AN OBSERVATIONAL COHORT STUDY WITH 804 PATIENTS.

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, 2017

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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