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:
- Serum basal cortisol level <5µg/dL confirms the presence of adrenal insufficiency.
Sequence of Diagnostic Studies
The various investigations must be performed simultaneously or in sequential order.:
- Prove the existence of adrenal insufficiency i.e. Syndromic Diagnosis.
- Determine the nature of adrenal insufficiency i.e. Primary, Secondary, Tertiary Adrenal insufficiency by identifying the location of the defect in the HPA axis.
- 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
- ↑ 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.
- ↑ https://www.elsevier.es/index.php?p=revista&pRevista=pdf-simple&pii=S2173509314700698