ACTH stimulation test


The ACTH test assess the functioning of the adrenal glands’ stress response by measuring the adrenal response to adrenocorticotropic hormone (ACTH; corticotropin) or another corticotropic agent.



ACTH is a hormone produced in the anterior pituitary gland that stimulates the adrenal glands to release cortisol, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and aldosterone.



A small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone,  that the adrenals produce in response is measured.



The test diagnoses or exclude primary and secondary adrenal insufficiency, Addison’s disease, and related conditions.



The ACTH stimulation test can quantifying adrenal insufficiency, and can distinguish whether the cause is adrenal:low cortisol and aldosterone production or pituitary: low ACTH production).



The test is extremely sensitive, 97% at 95% specificity to primary adrenal insufficiency.



For secondary adrenal insufficiency sensitivity is 57-61% at 95% specificity.



Testing can be  a low-dose short test, a conventional-dose short test, or as a prolonged-stimulation test.



Low-dose short test: 1 μg of an ACTH drug is injected into the patient. 



In the conventional-dose short test, 250 μg of drug are injected. 



Short tests last for about an hour and each test provides the same information, as the cortisol response of the adrenals is the same for the low-dose and conventional-dose tests.



The prolonged-stimulation test can last up to 48 hours, and can differentiate between primary, secondary, and tertiary adrenal insufficiency, but  is rarely performed.



Stress, recently administered radioisotope scans, spironolactone, contraceptives, licorice, estrogen, androgen and progesterone therapy may also affect both aldosterone and cortisol stimulation test results. 



To stimulate aldosterone, consumption of salt should be reduced to a minimum, and foods high in sodium avoided for hours prior to testing. 



Common reactions to ACTH test are nausea, anxious sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations and facial flushing but disappear within a few hours.



Rare but serious side effects include: rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat.



In healthy individuals, the cortisol level should increase above 18-20 μg/dl within 60 minutes on a 250 mcg cosyntropin stimulation test.



In Addison’s disease, both the cortisol and aldosterone levels are low, and the cortisol will not rise during the cosyntropin stimulation test



In secondary adrenal insufficiency, exogenous steroid administration suppressed  pituitary production of ACTH or due to primary pituitary disorder causing insufficient ACTH production, the adrenal glands will atrophy over time and cortisol production will fall and patients will fail stimulation testing. 



Measuring a morning, fasting ACTH level helps assess for the etiology of adrenal insufficiency.



For  primary adrenal insufficiency and Addison’s disease ACTH  levels will be high, well above upper limits of reference range.



In secondary adrenal insufficiency


ACTH will be low, usually below 35, but most people with secondary fall within the range limit: inappropriately normal for the low cortisol level.



The ACTH stimulation test can be used to test adrenal production of aldosterone at the same time as cortisol to also help in determining if primary or secondary hypoaldosteronism is present.



Human ACTH has a stimulatory effect on aldosterone.



Then aldosterone response can be easily measured in blood serum, and,  should double from a respectable base value of around 20 ng/dl.



The aldosterone response in the ACTH stimulation test is blunted or absent in patients with primary adrenal insufficiency including Addison’s disease.



The aldosterone rise is less than double the base value thus indicating primary hypoaldosteronism with low sodium, high potassium and renin enzyme and is an indicator of primary adrenal insufficiency or Addison’s disease.



Aldosterone levels with a cortisol stimulation that doubled or more, confirms a diagnosis of secondary adrenal insufficiency. 














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