ACTH stimulation test

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Overview
The ACTH stimulation test (also called the short Synacthen test) is a medical test performed to assess the functioning of the adrenal glands. Specifically, it is used to diagnose or exclude adrenal insufficiency, Addison's disease and related conditions. It involves the injection of synthetic adrenocorticotropic hormone (ACTH) and measuring the amount of cortisol and sometimes aldosterone the adrenals produce in response. Apart from objectivating adrenal insufficiency, it can also distinguish the various causes.

Method of preparation and administration
The patient should fast 12 hours before the test which should be done before 10 am, but as close to 7 am as possible. If the patient is already on a glucocorticoid, DHEA, pregnenolone or adrenal extract supplement, they should be off of these for at least 2 weeks after safely weaning. Stress and recently administered radioisotope scans can artificially increase levels and may invalidate test results. Spironolactone, contraceptives, estrogen, androgen 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 the test. This is to allow aldosterone to rise as far as possible. Women must test aldosterone in the first week of their cycle. The test procedure should be explained to the patient well before the test is performed.

The patients blood is drawn to get a starting or base cortisol level (serum ACTH should also be tested), next synthetic ACTH (Synacthen aka Tetracosactide or Cortrosyn aka Cosyntropin) is injected. Approximately 20 mg of heparinized venous blood is collected (in a red top tube to be chilled after last blood draw and shipped on ice to the lab immediately) is drawn 30 min, sometimes 45 min, and at 60 minutes after the synthetic ACTH has been injected. The test must be done for at least 60 minutes. In healthy adrenal function, the cortisol level should double within 60 minutes. If the cortisol level was a 25 before the stimulation (base level), after the stimulation should reach at least 50. Most patients feel nothing during or after the test, but flushed skin, anxiety and nausea and even an increased sense of well being are possible.

Method and interpretation for cortisol stimulation
In primary adrenal insufficiency, the base cortisol level usually starts at least a little lower, such as 15 (can be much lower). If the ACTH stimulation test raises cortisol level to 20, that would not be doubling and support the diagnosis of primary adrenal insufficiency.

In secondary adrenal insufficiency, the base cortisol can double, triple, quadruple or more from a low base value. Other examples reported include quintupling (5 stimming to 25 ng/dl, 6 stimming to 30), sextupling (4 stimming to 24, 5 stimming to 30), septupling (0.7 stimming to 4.9) and decupling (2 stimming to 20, 2.7 stimming to 27.6) and recently a stim that almost tridecupled (1.25 - 16 went up 12.8 times) and a stimulation that quadecupled (went up 14 times 1.7 stimming to 24, after 1 1/2 hours reached 27.5 for sexdecupling). These examples illustrate how extreme secondaries ACTH stimulation test can be. Most secondaries only double or triple and usually start with a base cortisol value of at least 10. The base cortisol can be very low because of the bodies lack of natural ACTH. When the synthetic ACTH is given in the test, the patients adrenals go hog wild because they can work, just not getting enough ACTH from the pituitary gland.

Some have reported their first ACTH stimulation test doubled or more from a low base cortisol value, but another test done later suggested they are really primary adrenal insufficient (cortisol value less than doubled). Many have reported their doctor changed their diagnosis from secondary to primary adrenal insufficiency "I guess you were primary the whole time". In secondary adrenal insufficiency, if the adrenals lack ACTH for enough time, adrenal cortisol production can atrophy, thus no longer rise in an ACTH stimulation with serum ACTH being in the lower half of the range. It is proper to continue with the secondary diagnosis.

The ACTH test is usually the final say in whether you have adrenal insufficiency, but most doctors are only looking for Addison's disease. If the test does not show Addison's (for example, in true Addison's, the stimulation may start at 3 and rise to 4 or 6 rising to 8), then doctors see the stimulation as showing the adrenals are working. They fail to recognize any degree of adrenal insufficiency between Addison's and healthy adrenal function. Many patients with secondary adrenal insufficiency are missed because most doctors see doubling or more even from a low base cortisol value with low acth being ok, not recognizing this indicates low ACTH production.

The ACTH serum test should always be given at the same time as the ACTH stimulation. This test measures how much ACTH the pituitary is making. ACTH serum and ACTH stimulation test together can give a clearer picture, especially if one is secondary adrenal insufficient.

In primary adrenal insufficiency (including Addison's), ACTH serum will be at the top of the range or above range. Sometimes in Addison's disease, ACTH will be way above range as high as the hundreds and even 1000's and 2000's.

In secondary adrenal insufficiency, serum ACTH will usually be in the bottom half of the range to the very bottom, but not usually below the range, but values can reach into the low 40's (98% of secondaries are in range on the serum ACTH). A healthy serum ACTH value should be just into the upper third of the range (assuming a range of 10 - 60 as they almost always were until about 3 years ago).

Method and interpretation for aldosterone stimulation
The ACTH stimulation test is occasionally used to stimulate the production of aldosterone at the same time as cortisol to also help in determining if primary (hyperreninemic) or secondary (hyporeninemic) hypoaldosteronism in adrenal insufficiency is present. Natural human ACTH has a small effect on aldosterone, but the amount of synthetic ACTH given in stimulation is equivalent to more than a whole days production of natural ACTH, so the aldosterone response can be easily measured. 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 primary adrenal insufficiency, the aldosterone base value will be lower (low teens or less) and rise to less than double the base value. If aldosterone does double or more from a low base value, that suggests secondary hypoaldosteronism and along side the cortisol stimulation can help support the diagnosis of secondary adrenal insufficiency.

In secondary adrenal insufficiency, aldosterone production can go up by several factors from a low base value. Decupling of aldosterone in the ACTH stimulation test is possible (ie 2 ng/dl stimming to 20). Like the cortisol stimulation, many doctors lack knowledge of how to properly interpret for secondary hypoaldosteronism and think this result is fantastic. Usually doubling to quadrupling from a low base aldosterone value is what is seen in secondary adrenal insufficiency.

Additional Links

 * Prueba de estimulación con ACTH
 * Test de stimulation à l’ACTH