ACTH Stimulation Test
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ACTH stimulation testThe ACTH stimulation test (also called the cosyntropin test or tetracosactide test) is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone (ACTH).[1][2] ACTH is a hormone produced in the pituitary gland that stimulates the adrenal glands to release cortisol.[2] During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone, the adrenals produce in response is measured.[3] This test may cause mild to moderate side effects in some individuals.[4][5] This test is used to diagnose or exclude primary and secondary adrenal insufficiency, Addison's disease and related conditions.[2] In addition to quantifying adrenal insufficiency, the test can distinguish whether the cause is adrenal (low cortisol and aldosterone production) or pituitary (low ACTH production).[1] The ACTH stimulation test is recognized as the gold standard assay of adrenal insufficiency, although this test is primarily used to determine the presence of Addison's disease and pituitary impairment.[6] If the test does not show Addison's, the test interpreter may see it as showing the adrenal glands are working, not recognizing any degree of adrenal insufficiency between Addison's (the worst degree of adrenal insufficiency) and healthy adrenal function.[citation needed] The test is extremely sensitive (97% at 95% specificity) to primary adrenal insufficiency, but less so to secondary adrenal insufficiency (57-61% at 95% specificity); while secondary adrenal insufficiency may thus be dismissed by some interpreters on the basis of the test, additional testing may be called for if probability of secondary adrenal insufficiency is particularly high.[1] Adrenal insufficiency is a potentially life-threatening condition. Treatment should be initiated as soon as the diagnosis is confirmed, or sooner if the patient presents in apparent adrenal crisis.[7] Versions of the testThis test can be given as a low-dose short test, a conventional-dose short test, or as a prolonged-stimulation test. In the 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. Both of these short tests last for about an hour and provide the same information. Studies have shown the measured stress response of the adrenals is the same for the low-dose and conventional-dose tests.[8] The prolonged-stimulation test, which is also called a long conventional-dose test, can last up to 48 hours. This form of the test can differentiate between primary, secondary, and tertiary adrenal insufficiency. This form of the test is rarely performed because earlier testing of cortisol and ACTH levels in association with the short test may provide all the necessary information.[7] PreparationThe person must fast at least 8 hours before the test which should be started by 10 am, but as close to 7 am as possible. The test shouldn't be given if on glucocorticoids, pregnenolone, or adrenal extract supplement as these will affect test results. Stress and recently administered radioisotope scans can artificially increase levels and may invalidate test results. Spironolactone, contraceptives, licorice, estrogen, androgen (including DHEA) and progesterone therapy may also affect both aldosterone and cortisol stimulation test results. If aldosterone is to be stimulated, salt and foods significant in sodium must be fasted for 24 hours prior to testing. This allows aldosterone to rise as far as possible. Women must test the first week of their cycle or aldosterone (and occasionally cortisol) results may appear ok in the last half of the cycle when progesterone is higher (progesterone breaks down into aldosterone and cortisol).[9] AdministrationBlood is drawn to get a starting or base cortisol (ACTH is also tested from this draw) and or aldosterone level. Next, synthetic ACTH (Synacthen aka Tetracosactide or Cortrosyn aka Cosyntropin) is injected. Approximately 20 mL of heparinized venous blood is collected at 30 and 60 minutes after the synthetic ACTH injection.[10][11] All blood samples are kept on ice and sent immediately to the laboratory for testing.[12] Potential side effectsNormal reactions that should be reported are nausea, anxiety, sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations (a fast or fluttering heart beat) and facial flushing (may also include arms and torso), but should disappear within a few hours.[4][5] Rarely seen, but serious side effects include rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat.[5] Although uncommon, some people report feeling better or sense of well being after the test. Interpretation of results
Cortisol stimulationIn healthy individuals, the cortisol level should double from a value at least in the 20s within 60 minutes. If the cortisol level was a 25 before the stimulation (base level), after the stimulation it should reach at least 50 ug/dl.
The base cortisol level in people with adrenal insufficiency is usually in the mid teens. If the ACTH stimulation test raises cortisol level to 20 ug/dl, that is not doubling and supports the diagnosis of primary adrenal insufficiency. In Addison's, base cortisol is well below 10 ug/dl and rises no more than 25 percent.
ACTH may stimulate cortisol by a factor doubling, tripling, quadrupling or more from a low base value in patients suffering from secondary adrenal insufficiency. Stimulation resulting in a greater than 14-fold increase in serum concentration over 30 minutes has been reported; however in most cases serum cortisol levels only double or triple and most start with a base cortisol value of at least 10 ug/dl. The lower the base cortisol value, the more likely the patient's cortisol will stimulate by a high factor if they are secondary adrenal insufficient.[12] In some instances, a second test performed later can suggest primary adrenal insufficiency (cortisol value less than doubled). The diagnosis may be changed from secondary to primary adrenal insufficiency or to include primary adrenal insufficiency. In secondary adrenal insufficiency, if the adrenal glands lack ACTH for enough time, cortisol production can atrophy[13] and fail to rise to a value at least double the base cortisol value. It is proper to continue with the diagnosis of secondary adrenal insufficiency. If secondary adrenal insufficiency is diagnosed, the insulin tolerance test (ITT) or the CRH (Corticotropin-releasing hormone) stimulation test can be used to distinguish between a hypothalamic (tertiary) and pituitary (secondary) cause, but is rarely used in clinical practice.[13] ACTH plasma test plus cortisol stimulationAn ACTH plasma test should always be given at the same time as the ACTH stimulation, although many doctors consider the test inaccurate. This test measures how much ACTH the pituitary gland is producing. A healthy ACTH value should be just into the upper third of the range (assuming a range of 10–60 ng/L). The ACTH plasma and ACTH stimulation test together can give a clearer picture, especially for secondary adrenal insufficiency.[10]
ACTH will be high[10] - either at the top or above range. In Addison's disease, ACTH may be way above range and may reach the hundreds. In very rare cases can reach the 1000s and 2000s.
ACTH will be low[10] - Usually below 35, but most people with secondary fall within the range limit. Although uncommon, values for ACTH can reach into the low 40s. In some cases, actual cause of low ACTH is from low CRH in the hypothalamus. It is possible to have separate ACTH and CRH impairment such as can happen in a head injury.[14] Aldosterone stimulationThe ACTH stimulation test is occasionally used to test adrenal production of aldosterone at the same time as cortisol to also help in determining if primary (hyperreninemic) or secondary (hyporeninemic) hypoaldosteronism is present.[3] Human ACTH has a slight stimulatory effect on aldosterone[15], but the amount of synthetic ACTH given in the stimulation is equivalent to more than a whole days production of natural ACTH, so the aldosterone response can be easily measured in blood serum.[16] Same as cortisol, aldosterone should double from a respectable base value (around 20 ng/dl, must fast salt 24 hours and sit upright for blood draw) in a healthy individual.
The aldosterone response in the ACTH stimulation test is blunted or absent in patients with primary adrenal insufficiency including Addison's disease.[3] The base value is usually in the mid teens or less and rise to less than double the base value thus indicating primary hypoaldosteronism (sodium low, potassium and renin enzyme will be high) and is an indicator of primary adrenal insufficiency or Addison's disease.
Aldosterone response of several factors from a low base value. This factoring indicates secondary hypoaldosteronism (sodium low, potassium and renin enzyme will be low). Usually doubling to quadrupling from a low base aldosterone value is what is seen in secondary adrenal insufficiency. Decupling of aldosterone in the ACTH stimulation test is possible (ie 2 ng/dl stimming to 20).[17] A result of doubling of more of aldosterone may help in tandem with a cortisol stimulation that doubled or more confirm a diagnosis of secondary adrenal insufficiency. In rare cases, an aldosterone stimulation which did not double, but with the presence of low potassium, low renin and low ACTH indicates atrophy of aldosterone production from the prolonged lack of renin. Similar to the cortisol stimulation in ACTH deficiency, the test interpreter may lack knowledge of how to properly interpret for secondary hypoaldosteronism and think a result of aldosterone doubling or more from a low base value is good. Other hormones and chemicals that will rise in the ACTH stimulation test
Simple diagnostic chart
See also
References
External links
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