Adrenal insufficiency diagnostic study of choice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayeesha Kattubadi, M.B.B.S[2]

Overview

The ACTH stimulation test is considered the diagnostic test of choice.

Diagnostic Study of Choice

Study of choice

The Short ACTH stimulation test is considered as the gold standard in diagnosing primary adrenal insufficiency, but not secondary adrenal insufficiency. Insulin hypoglycemic test was considered the gold standard test for the diagnosis of adrenal insufficiency. However, it is not routinely used now as it can cause dangerous hypoglycemia and is expensive. [1] [2] The diagnostic test of choice is serum basal cortisol measurement. Cortisol secretion follows a circadian rhythm with a nadir at midnight and a peak between 6-8 AM, serum basal cortisol measurement should be taken between 8 AM-9 AM. Alternately, salivary cortisol, and urine free cortisol can also be used for basal hormone level measurement.

Investigations:

  • Among the patients who present with clinical signs of adrenal insufficiency, the insulin hypoglycemic test is the most specific and sensitive test for the diagnosis.
  • Among the patients who present with clinical signs of adrenal insufficiency, the serum basal cortisol level of <5µg/dL is the highly sensitive test for diagnosis.
Diagnostic results

The following finding on performing serum basal cortisol is confirmatory for adrenal insufficiency:


Sequence of Diagnostic Studies

The various investigations must be performed simultaneously or in sequential order.:

  1. Prove the existence of adrenal insufficiency i.e. Syndromic Diagnosis.
  2. Determine the nature of adrenal insufficiency i.e. Primary, Secondary, Tertiary Adrenal insufficiency by identifying the location of the defect in the HPA axis.
  3. Determine the cause i.e. etiological diagnosis.

Tests used in syndromic diagnosis: Serum basal cortisol, salivary cortisol, urinary cortisol.

Dynamic tests: They are used in patients with indeterminate levels of serum basal cortisol i.e.5 µg/dL to 18 µg/dL. The different types of dynamic tests are as follows:

Name of the test Insulin Hypoglycemia test ACTH stimulation test Low dose ACTH stimukation test Metyrapone stimulation Glucagon stimulation
Agent to be administered Regular insulin 0.1-1.15U/kg I.V Cosyntropin 250mcg I.V Consyntropin 1mcg I.V Metyrapone 30mg/kg P.O Glucagon 1mg I.M
Timing of sample collection 0-30-45-60-90 min 0-30-60 min 0-30-60 min 8 hours post metyrapone 90-120-150-180-210-240min
Parameter Tested Plasma cortisol Plasma cortisol Plasma cortisol 11 deoxycortisol Plasma cortisol
Comments Gold standard Safe Manual preparation Assesses whole HPA Less accurate

Diagnostic algorithm:

 
 
 
 
 
 
 
 
 
 
 
 
 
Adrenal Insufficiency suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum basal cortisol
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
<5 µg/dL
 
 
 
 
 
 
 
5-18 µg/dL
 
 
 
 
 
 
>18 µg/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
 
 
 
 
 
 
Dynamic tests
 
 
 
 
 
 
Rules out Adrenal Insufficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Primary Adrenal Insufficiency suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
Secondary Adrenal Insufficiency suspected
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACTH stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
ACTH stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum cortisol <18 µg/dL
 
Serum cortisol >18µg/dL
 
 
 
 
 
 
Serum cortisol <18 µg/dL
 
 
Serum cortisol 18-23µg/dL
 
 
Serum cortisol >23 µg/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
Rules out Adrenal Insufficiency
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
 
Indeterminate
 
 
Rules out Adrenal Insufficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Insulin hypoglycemic test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum cortisol <18µg/dL
 
Serum cortisol >18µg/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confirms Adrenal Insufficiency
 
Rules out Adrenal Insufficiency
 
 


Diagnosing the location of defect:

Primary Adrenal Insufficiency Secondary Adrenal Insufficiency
Clinical Hyperpigmentation of skin and mucous membranes No hyperpigmentation
Labs Hyperkalemia, Hyponatremia Hyponatremia
ACTH Increased to two times upper limit of normal Normal or decreased

Etiological diagnosis: Measure autoantibodies against 21-hydroxylase. If autoantibody-negative look for other causes.

Name of Diagnostic Criteria

There are no established criteria for the diagnosis of adrenal insufficiency.

References

  1. Bornstein, Stefan R.; Allolio, Bruno; Arlt, Wiebke; Barthel, Andreas; Don-Wauchope, Andrew; Hammer, Gary D.; Husebye, Eystein S.; Merke, Deborah P.; Murad, M. Hassan; Stratakis, Constantine A.; Torpy, David J. (2016). "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology & Metabolism. 101 (2): 364–389. doi:10.1210/jc.2015-1710. ISSN 0021-972X.
  2. https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698

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