Addison's disease laboratory findings

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

Overview

Diagnosis of Addison's disease is made by routine blood tests and specific tests. ACTH stimulation test is a specific test employed to determine the function of adrenal glands and to diagnose Addison's disease. The prominent finding of a rapid ACTH stimulation test includes failure of cortisol to rise in response to ACTH injection. Other routine laboratory tests employed include plasma cortisol level, serum ACTH level, plasma renin activity, aldosterone levels and serum biochemistry.

Laboratory Findings

Diagnosis of Addison's disease is made by routine blood tests and specific tests. The aim of these tests is to determine the levels of cortisol and then to establish the cause of deficiency.[1][2][3]

Diagnostic decision

Clinical setting Best initial test
Non-acute
Acute illness

Specific tests to determine adrenal gland function

ACTH Stimulation Test (Rapid ACTH Stimulation Test)

  • This is the most specific test for diagnosing Addison's disease.
  • In this test, blood cortisol, urine cortisol, or both are measured before and after a synthetic form of ACTH is given by injection.
  • It is called short, or rapid ACTH test because measurement of cortisol in blood is repeated 30 to 60 minutes after an intravenous ACTH injection.
  • 250 µg synthetic ACTH (cosyntropin) is administered intravenously or intramuscularly.
  • The normal response after an injection of ACTH is a rise in blood and urine cortisol levels.
  • Those with primary adrenal insufficiency fail to increase cortisol levels above 18 µg/dL; those with secondary or tertiary adrenal insufficiency also fail to achieve cortisol levels above 18 µg/dL as long as their condition has been present long enough to allow adrenal atrophy (about 2-4 weeks).
  • If a subnormal cortisol response occurs, ACTH measurement and other tests should distinguish between primary and secondary and tertiary causes
  • Patients with either form of adrenal insufficiency respond poorly or do not respond at all.
 
 
 
 
 
 
 
 
8 am cortisol
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
>15Ug/dL
 
 
 
 
3-15Ug/dL
 
 
 
 
<3Ug/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adrenal insufficiency is
ruled out
 
 
 
 
 
 
 
 
 
 
 
 
Measure ACTH
 
 
 
 
 
 
 
 
30 min cortisol during
cosyntropin stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
>18Ug/dL
 
 
 
 
 
 
<18Ug/dL
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adrenal insufficiency is ruled out
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adrenal insufficiency confirmed
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure ACTH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low/normal
 
 
 
 
 
 
 
 
Elevated
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Secondary
Adrenal insufficiency
 
 
 
 
 
 
 
 
Primary
Adrenal insufficiency

CRH Stimulation Test

  • When the response to the short ACTH test is abnormal, a "long" CRH stimulation test is required to determine the cause of adrenal insufficiency.
  • In this test, 1 μg synthetic CRH is injected intravenously and blood cortisol is measured before and 30, 60, 90, and 120 minutes after the injection.
  • There is some evidence that the low-dose ACTH test is more sensitive than the standard 250 μg test in identifying partial or mild cases of secondary or tertiary adrenal insufficiency
  • Patients with primary adrenal insufficiency have high ACTHs but do not produce cortisol.
  • Patients with secondary adrenal insufficiency have deficient cortisol responses but absent or delayed ACTH responses.
  • Absent ACTH response points to the pituitary as the cause; a delayed ACTH response points to the hypothalamus as the cause.

Routine investigations

Routine investigations include

Test Advantage Normal values Laboratory Finding
Plasma cortisol
  • Screening test for adrenal insufficiency
  • <3 µg/dL: suggests evidence of adrenal insufficiency
  • 3-18 µg/dL: non-diagnostic, although levels <10 µg/dL raise suspicion of adrenal insufficiency
  • >18 µg/dL precludes the diagnosis of adrenal insufficiency
Serum ACTH level
  • Helps to distinguish primary from secondary/tertiary adrenal insufficiency
  • ACTH: 5-30 ng/mL
  • In Addison disease: ACTH elevated (usually >60 ng/mL) in the face of a low or low-normal cortisol
  • In secondary/tertiary adrenal insufficiency: ACTH is low (usually <5 ng/mL) in the face of low cortisol
Plasma renin activity and aldosterone levels
  • A compensatory increase in PRA is the earliest response to mild aldosterone deficiency.
  • Normal PA (ng/dL) to PR (ng/mL/h) is less than 20 with plasma aldosterone levels less than 15 ng/dL.
Serum biochemistry
  • Simple, widely available test
In Addison disease:

References

  1. Chakera AJ, Vaidya B (2010). "Addison disease in adults: diagnosis and management". Am. J. Med. 123 (5): 409–13. doi:10.1016/j.amjmed.2009.12.017. PMID 20399314.
  2. Husebye ES, Allolio B, Arlt W, Badenhoop K, Bensing S, Betterle C, Falorni A, Gan EH, Hulting AL, Kasperlik-Zaluska A, Kämpe O, Løvås K, Meyer G, Pearce SH (2014). "Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency". J. Intern. Med. 275 (2): 104–15. doi:10.1111/joim.12162. PMID 24330030.
  3. Puttanna A, Cunningham AR, Dainty P (2013). "Addison's disease and its associations". BMJ Case Rep. 2013. doi:10.1136/bcr-2013-010473. PMC 3736622. PMID 23893277.



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